The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.

Fluoruro de estaño en el control de cavidades sin restauración en dientes temporales / Stannous fluoride in nonrestorative cavity control in primary teeth

Introducción: el control de cavidades sin restauración (NRCC, por sus siglas en inglés), es una opción de tratamiento conservador y no invasivo para dentina cariosa, sobre todo en dentición temporal. Una de las estrategias del NRCC es la remineralización. El fluoruro de estaño (FDE) puede considerarse, como una opción viable ya que existe evidencia de su eficacia cariostática. Objetivo: valorar al FDE como remineralizante alternativo en dentina de molares temporales, asociado al NRCC. Material y métodos: se efectuó un estudio clínico, epidemiológico, y descriptivo con preescolares voluntarios de 3 a 5 años de edad con consentimiento firmado de participación en el estudio, y que presentaron molares con ICDAS 5 y 6. La aplicación del FDE a 0.8%, la evaluación de la dureza de la dentina con los criterios de Nyvad, y el diagnóstico del estado pulpar, la efectuó un operador entrenado para esta finalidad. Se aplicó un análisis estadístico descriptivo y uno no paramétrico. Resultados: el efecto cariostático producido por el FDE a 0.8%, sobre dentina afectada de molares temporales de niños mexicanos fue estadísticamente significativo durante cinco meses. Conclusiones: la aplicación de fluoruro de estaño puede considerarse como una alternativa de tratamiento cariostático asociado al NRCC para niños de 3 a 5 años de edad (AU)

Introduction: nonrestorative cavity control (NRCC), is a conservative and non-invasive treatment option for carious dentin, especially in primary dentition. One of the NRCC strategies is remineralization. Stannous Fluoride (SDF) can be considered as a viable option since there is evidence of its cariostatic efficacy. Objective: to evaluate FDE as an alternative remineralizing agent in the dentin of primary molars, associated with NRCC. Material and methods: a clinical, epidemiological, and descriptive study was carried out with preschool volunteers aged 3 to 5 years with signed consent to participate in the study, and who presented molars with ICDAS 5 and 6. The application of FDE at 0.8%, the evaluation of dentin hardness with the Nyvad criteria, and the diagnosis of pulp status, was carried out by an operator trained for this purpose. A descriptive and non-parametric statistical analysis was applied. Results: the cariostatic effect produced by 0.8% FDE on affected dentin of primary molars of Mexican children was statistically significant for five months. Conclusions: the application of stannous fluoride can be considered as an alternative cariostatic treatment associated with NRCC for children 3 to 5 years of age (AU)

Golgi Transport 1A Promotes Cell Proliferation and Metastasis of Papillary Thyroid Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo investigate the expression level of Golgi transport 1A （GOLT1A） in thyroid carcinoma and its effects on the proliferation， migration， invasion， and epithelial-mesenchymal transition （EMT） of thyroid carcinoma cells. MethodsThe expression of GOLT1A in thyroid carcinoma was analyzed online by tumor immune estimation resource （TIMER）， the University of Alabama at Birmingham cancer data analysis portal （UALCAN）， gene expression profiling interactive analysis 2 （GEPIA2）. The expression level of GOLT1A in thyroid carcinoma cells was detected by real-time fluorescence quantitative polymerase chain reaction （RTFQ-PCR） and western blot. Cell counting kit-8 （CCK-8） assay， colony formation assay， and transwell assay were used to detect the effects of GOLT1A expression on the proliferation， migration， and invasion of thyroid carcinoma cells. Western blot assay was used to detect the effect of GOLT1A on the expression of EMT-related genes including E-cadherin， vimentin， and N-cadherin. ResultsThe online analysis of GEPIA2， TIMER， and UALCAN showed that the expression of GOLT1A was higher in thyroid carcinoma than in normal tissues， and the expression of GOLT1A in thyroid carcinoma cells was significantly higher than in normal control cells. Knockdown of GOLT1A inhibited TPC1 cell proliferation， migration， and invasion. The expression of E-cadherin increased and the expressions of N-cadherin and vimentin decreased in GOLT1A knockdown TPC1 cells. Overexpression of GOLT1A promoted BCPAP cell proliferation， migration， and invasion. The expression of E-cadherin decreased and the expressions of N-cadherin and vimentin increased in GOLT1A overexpression BCPAP cells. ConclusionGOLT1A is highly expressed in thyroid carcinoma and can promote the proliferation， migration， and invasion of thyroid carcinoma cells.

Down-regulation of METTL5 inhibits proliferation, migration and invasion of triple-negative breast cancer cells through Wnt/6-catenin signaling pathway / 中国药理学通报

Aim To investigate the role and potential mechanism of methyltransferase-like 5 (METTL5) in triple-negative breast cancer (TNBC) . Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot. After shRNA targeting METTL5 (shRNAMETTL5) was transfected into TNBC cells, cell proliferation, migration and invasion were detected by CCK-8, colony formation, wound healing and Transwell assays, respectively. Western blot was used to detect the expression of Wnt/p-catenin signaling-related key proteins. A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/p-catenin signaling activity in vivo. Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines (P < 0. 01) . Knockdown of METTL5 significantly inhibited the proliferation, migration and invasion of TNBC cells and reduced the expression of Wnt/p-catenin signaling molecules (3-catenin, cyclin Dl, matrix metalloproteinase (MMP) -2 and MMP-7 (all P < 0. 01) . Knockdown of METTL5 reduced tumor growth and Wnt/pcatenin signaling activity in vivo. Conclusions Knockdown of METTL5 can inhibit the proliferation, migration and invasion of TNBC cells, which may be related to the inhibition of Wnt/p-catenin signaling pathway.

Effects of polydatin on the cell proliferation，migration，invasion and tumor growth of AML / 中国药房

OBJECTIVE To investigate the effects of polydatin （PD） on cell proliferation， migration， invasion and tumor growth of acute myeloid leukemia （AML）. METHODS Human AML cell KG-1 were divided into normal group， PD low-， medium- and high-concentration groups （10， 30， 60 μmol/L PD）， SQ22536 group [cyclic adenosine monophosphate （cAMP） inhibitor， 100 μmol/L]， high concentration of PD+SQ22536 group （60 μmol/L PD+100 μmol/L SQ22536）. The effects of PD on cell activity， apoptotic rate， invasion and migration ability， cAMP level， the expression of epithelial-mesenchymal transition （EMT） related proteins and protein kinase A （PKA） were investigated. Using BALB/c nude mice as subjects， a transplanted tumor model of AML nude mice was induced by subcutaneous inoculation of KG-1 cell suspension and then divided into control group， PD group， SQ22536 group and PD+SQ22536 group （with 6 mice in each group）. The effects of PD on tumor volume and mass were measured. RESULTS Compared with the normal group or control group， the cell viabilities， the number of migrating cells， the number of invasive cells， the relative expressions of vimentin and Snail as well as the tumor volume and mass were decreased significantly in PD groups， while the apoptotic rates， cAMP levels， the relative expressions of E-cadherin and PKA were significantly increased， with a dose-dependent manner （P＜0.05）. SQ22536 had opposite effects on cells and nude mice compared to PD， and could significantly reverse the anti-tumor activity of PD （P＜0.05）. CONCLUSIONS PD may inhibit the proliferation， migration， invasion and EMT process of KG-1 cells， induce apoptosis， and inhibit tumor growth， by activating the cAMP/PKA signaling pathway， thereby exerting anti-AML effects.

Effect of picroside Ⅱ on the malignant progression of non-small cell lung cancer / 中国药房

OBJECTIVE To investigate the effect and mechanism of picroside Ⅱ on the malignant progression of non-small cell lung cancer （NSCLC）. METHODS A549 cells were divided into the control group， picroside Ⅱ low-， medium- and high- concentration groups， K6PC-5 [sphingosine kinase 1 （SPHK1） activator] group， and picroside Ⅱ high-dose+K6PC-5 group. Cell proliferation， migration and invasion were detected. Besides， the expression of proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase-2 （MMP-2）， MMP-9， SPHK1， sphingosine-1-phosphate receptor 3 （S1PR3） and extracellular signal-regulated kinase 1/2 （ERK1/2） protein in the cells were also observed. BALB/c nude mice were subcutaneously inoculated with A549 cell suspension to establish NSCLC xenograft models. Then they were assigned to the nude mouse-control group， nude mouse-picroside Ⅱ low-， medium- and high-dose groups， nude mouse-K6PC-5 group， and nude mouse-picroside Ⅱ high-dose+K6PC-5 group （with 5 mice in each group） to investigate the effect of picroside Ⅱ on their tumor mass and volume. RESULTS Compared with the control group， the OD450 values， EdU-positive cell rates， scratch healing rates， cell invasion number， and the relative expression levels of PCNA， MMP-2， MMP-9， SPHK1， S1PR3 and ERK1/2 protein in the low-， medium- and high-concentration groups of picroside Ⅱ were significantly decreased. Compared with the nude mouse-control group， the tumor mass and volume in the nude mouse-low-， medium- and high-dose groups of picroside Ⅱ were significantly decreased or shrunk. The changes of above indicators were concentration/dose-dependent （P＜0.05）. The changing trend of the corresponding indicators in the K6PC-5 ZYTS181） group and the nude mouse-K6PC-5 group was opposite （P＜0.05）. Compared with the picroside Ⅱ high-concentration group or the nude mice-picroside Ⅱ high-dose group， the above quantitative indicators in the picroside Ⅱ high- concentration+K6PC-5 group cells and the nude mouse-picroside Ⅱ high-dose+K6PC-5 group nude mice were significantly increased or enlarged （P＜0.05）. CONCLUSIONS Picroside Ⅱ may inhibit the malignant progression of NSCLC by inhibiting SPHK1/sphingosine-1-phosphate/S1PR3 signaling pathway.

The association of visceral pleural invasion with skip N2 metastasis on clinical stage IA NSCLC

Abstract Background Lung lymphatic drainage occurs mainly through a peribronchial path, but it is hypothesized that visceral pleural invasion could alter this path. This study aims to investigate the association between visceral pleural invasion, node upstaging, and N2 skip metastasis and the impact on survival in a population of patients with non-small cell lung cancer of 3 cm or smaller. Methods We retrospectively queried our institutional database of lung cancer resection for all patients with clinical stage IA NSCLC between June 2009 and June 2022. We collected baseline characteristics and clinical and pathological staging data. Patients were classified into two groups: The non-VPI group with negative visceral pleural invasion and the VPI group with positive. The primary results analyzed were the occurrence of nodal upstaging, skip N2 metastasis and recurrence. Results There were 320 patients analyzed. 61.3 % were women; the median age was 65.4 years. The pleural invasion occurred in 44 patients (13.7 %). VPI group had larger nodules (2.3 vs. 1.7 cm; p < 0.0001), higher 18F-FDG uptake (7.4 vs. 3.4; p < 0.0001), and lymph-vascular invasion (35.7 % vs. 13.5 %, p = 0.001). Also, the VPI group had more nodal disease (25.6 % vs. 8.7 %; p = 0.001) and skip N2 metastasis (9.3 % vs. 1.8 %; p = 0.006). VPI was a statistically independent factor for skip N2 metastasis. Recurrence occurred in 17.2 % of the population. 5-year disease-free and overall survival were worse in the VPI group. Conclusions The visceral pleural invasion was an independent factor associated with N2 skip metastasis and had worse disease-free and overall survival.

circCPA4 induces malignant behaviors of prostate cancer via miR-491-5p/ SHOC2 feedback loop

ABSTRACT Objective: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. Methods: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. Results: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. Conclusion: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.

The association of polypoid growth pattern with lymphnode involvement in endometrioid type endometrial adenocarcinoma

Background: Tumor size is an independent predictor of lymph node metastasis and survival in the endometrioid type endometrial adenocarcinoma (EC). However, some of the ECs tend to grow towards the cavity in the polypoid pattern, which can reach very large sizes. In this study, we aimed to analyze the association of growing in the polypoid pattern of the tumor with the proportion of lymph node metastasis and extrauterine tumor spread. Methods: Four hundred seven patients were analyzed retrospectively. The effect of tumor size, tumor growing pattern, myometrial invasion, grade, and lymphovascular space invasion on the lymph node metastasis and extrauterine tumor spread were investigated. Statistical analysis consisted of unpaired t?tests for parametric data and Mann Whitney?U test for non?parametric data, whereas the Chi?square test for categorical variables. Logistic Regression, Cox Regression and multivariate analysis were used to estimate the risk predictors. Results: No association was found between the growing in polypoid pattern and lymph node metastasis (P > 0.05). In the analysis of endometrioid type EC patients who had myometrial invasion less than � as a subgroup, no association was found between the growing pattern and lymph node metastasis and extrauterine disease. Tumor size was found to be a statistically significant predictor of lymph node metastasis and extrauterine disease (P < 0.05). Conclusions: Lymphovascular space invasion, grade, and myometrial invasion are associated with a higher proportion of lymph node metastasis. The polypoid growth pattern of the tumor does not correlate with any histopathological parameters

MicroRNA-150-5p inhibits the proliferation and invasion of human larynx epidermiod cancer cells though regulating peptidyl-prolyl cis/trans isomerase

Abstract Objective This study aimed to investigate the molecular mechanism of miR-150-5p regulating the malignant biological behavior of Human Epidermoid cancer cell (HEp-2) by targeting peptidyl-prolyl cis/trans isomerase NIMA-Interacting-1 (PIN1). Methods Firstly, qRT-PCR and Western blot were adopted to detect the expression levels of miR-150-5p and PIN1 in cancer tissue and paracancerous tissues of patients with LSCC, and those in human bronchial epithelial cells (16 HBE) and HEp-2. Next, the targeted relationship between miR-150-5p and PIN1 was assessed by bioinformatics website and dual-luciferase reporter assay, followed by their correlation analysis. Besides, after interfering with miR-150-5p or PIN1 expression in HEp-2 cells, CCK-8, cell colony formation assay, and transwell assay were utilized to detect the proliferation, viability, and invasion of cells, respectively. Subsequently, the protein levels of MMP-2, MMP-9, and EMT-related proteins in HEp-2 cells were checked by Western blot. Results Expression of miR-150-5p was down-regulated in LSCC tissues and HEp-2 cells. Moreover, miR-150-5p suppressed proliferation and invasion of HEp-2 cells, affected protein expression related to MMP and EMT, thereby inhibiting development of cancer. The expression of PIN1 was significantly increased in cancer tissues and HEp-2 cells, and there was a targeted relationship and negative correlation between miR-150-5p and PIN1 in cancer tissue. However, overexpression of PIN1 could reverse the effect of miR-150-5p on the proliferation and invasion of HEp-2 cells. Conclusion In a nutshell, there is a targeted relationship between PIN1 and miR-150-5p. Besides, miR-150-5p can inhibit the proliferation and invasion of HEp-2 cells by regulating the expression of PIN1. Level of evidence 3.

Inhibitory Effect of UHRF1 on Invasion and Migration of Colorectal Cancer Cells via WNT/MMP9 Signaling Pathway / 肿瘤防治研究

Objective To explore the relationship of UHRF1 with the clinicopathological characteristics of colorectal cancer (CRC) patients, as well as the effects of lentivirus transfection overexpression and knockdown of UHRF1 on the proliferation, invasion, and migration of CRC cells and the possible signaling pathways. Methods The expression of UHRF1 mRNA and protein in CRC tissues and adjacent tissues was detected by immunohistochemical staining and RT-PCR. The effects of the constructed UHRF1 overexpression- and knockdown-group cells on the expression of UHRF1, related molecules in the WNT signaling pathway, and MMPR9 were examined by Western blot and RT-PCR. EDU and Transwell assays were used to detect changes in the proliferation, migration, and invasion of CRC cells. Results (1) In the TCGA database and clinical data, the mRNA and protein expression levels of UHRF1 in CRC cancer tissues were significantly higher than those in adjacent normal tissues. UHRF1 expression was closely correlated with TNM stage, N stage, and M stage. Patients with low UHRF1 expression in TCGA had better 5-year OS and disease-specific survival. The area under the ROC curve of UHRF1 for predicting 1-, 3-, and 5-year OS were 0.634, 0.652, and 0.771, respectively. The 3-year OS in the clinical data also showed the same survival benefit. UHRF1 overexpression was a poor prognostic factor for CRC patients. (2) After UHRF1 overexpression, the expression of WNT3a, GSK3β, and MMP9 in SW480 cells significantly increased, whereas the expression of p-β-catenin decreased (P < 0.05). After UHRF1 knockdown, the expression of WNT3a, GSK3β, and MMP9 in HCT116 cells decreased, whereas the expression of p-β-catenin increased (P < 0.05). The "rescue" experiment with IWP-2 and HLY78 can produce consistent results. (3) Compared with the control group, the cell proliferation, migration, and invasion abilities of the UHRF1 overexpression group were enhanced. After IWP-2 treatment, the cell proliferation, migration, and invasion abilities were inhibited. Knockdown experiment exhibited the reverse results to overexpression experiment. Conclusion UHRF1 may play an important role in the occurrence and development of CRC. UHRF1 overexpression may be a poor prognostic factor for CRC patients. UHRF1 may affect the proliferation, migration, and invasion of CRC cells through the WNT/MMP9 signaling pathway.

Effects of KCNQ1OT1 Gene Knockout Combined with Bruceine D on Proliferation, Migration, and Invasion of Breast Cancer MDA-MB-231 Cells / 肿瘤防治研究

Objective To explore the effect of KCNQ1OT1 gene knockout combined with bruceine D on the proliferation, migration, and invasion of breast cancer MDA-MB-231 cells. Methods Cell Counting Kit-8, wound healing, and Transwell invasion assay were used to detect the effects of bruceine D and siKCNQ1OT1 on the viability, migration, and invasion of MDA-MB-231 cells. Effect of bruceine D and siKCNQ1OT1 on the expression of KCNQ1OT1 in MDA-MB-231 cells was detected by qRT-PCR. Western blot was used to detect the effect of bruceine D and siKCNQ1OT1 on the expression of EMT-related proteins and CDC42, p-MKK7, MKK7 proteins in MDA-MB-231 cells. Results Bruceine D and siKCNQ1OT1 could significantly inhibit the viability, migration, and invasion of MDA-MB-231 cells, and the inhibitory effect was enhanced when they were combined (all P < 0.05); bruceine D downregulated the expression of KCNQ1OT1 in MDA-MB-231 cells (all P < 0.05); bruceine D combined with siKCNQ1OT1 significantly decreased CDC42, p-MKK7, N-cadherin, and Vimentin expression in MDA-MB-231 cells and increased the expression of E-cadherin (all P < 0.05). Conclusion Bruceine D combined with siKCNQ1OT1 significantly inhibit the proliferation, migration, invasion, and EMT of human breast cancer MDA-MB-231 cells, and its molecular mechanism may be related to the blocking of CDC42/MKK7 signaling pathway.

Effect of miR-524-5p on Epithelial-mesenchymal Transition in Esophageal Cancer Cells by Regulating HEG1 Expression / 肿瘤防治研究

Objective To investigate the mechanism and the effect of miR-524-5p regulating HEG1 expression on the proliferation and epithelial-mesenchymal transition of esophageal cancer cells. Methods The expression levels of miR-524-5p and HEG1 mRNA in esophageal cancer cells and normal esophageal epithelial cells were detected by qRT-PCR. KYSE30 cells were divided into miR-524-5p mimic group, miR-524-5p NC group, miR-524-5p mimic+pcDNA3.1 group, and miR-524-5p mimic+pcDNA3.1-HEG1 group. Non-transfected cells were set as the normal control group (group Control). CCK-8 method was applied to detect the proliferation ability of KYSE30 cells. Western blot analysis was conducted to detect the expression of proteins related to EMT, invasion, and migration and the HEG1 protein. Scratch and Transwell assays were applied to detect the migration and invasion abilities of KYSE30 cells. A dual-luciferase reporter gene was used to examine the targeting relationship between miR-524-5p and HEG1. Results miR-524-5p was lowly expressed in four esophageal cancer cell lines, namely, TE-1, KYSE30, KYSE150, and NEC (P < 0.05). KYSE30 cells with the lowest expression level were selected for subsequent experiments. HEG1 mRNA was highly expressed in four esophageal cancer cell lines (P < 0.05). The GEPIA database showed that HEG1 was highly expressed in esophageal cancer tumor tissues (P < 0.05). KYSE30 cells in the miR-524-5p mimic group had lower proliferation ability, colony formation number, mesenchymal marker protein expression, and migration and invasion abilities and upregulated epithelial marker protein E-cadherin level than cells in the miR-524-5p NC group (P < 0.05). The miR-524-5p mimic+pcDNA3.1-HEG1 group significantly reversed the inhibitory effect of overexpression of miR-524-5p on the proliferation, epithelial–mesenchymal transformation, invasion, and metastasis of KYSE30 cells (P < 0.05). The luciferase activity of cells in the miR-524-5p mimic and WT-HEG1 co-transfection groups was lower than that in the miR-524-5p NC and WT-HEG1 co-transfection groups (P < 0.05). Conclusion miR-524-5p is lowly expressed in EC cells and tissues. The overexpression of miR-524-5p can negatively regulate the expression of HEG1 in esophageal cancer cell line (KYSE30 cells) and reduce the proliferation, EMT process, and invasion and migration abilities of KYSE30 cells.

Effect of Porphyromonas gingivalis infection on IFNGR1 palmitoylation in esophageal cancer cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of Porphyromonas gingivalis (Pg) infection on IFNGR1 palmitoylation and biological behaviors of esophageal squamous cell carcinoma (ESCC) cells and the clinical implications.@*METHODS@#The expression levels of IFNGR1 protein in ESCC cell lines KYSE30 and KYSE70 were detected using Western blotting at 24 and 48 h after Pg infection, and 2-BP was used to detect IFNGR1 palmitoylation in the cells. KYSE70 cells with wild-type IFNGR1 (IFNGR1-WT cells) and with IFNGR1-C122A palmitoylation site mutation induced by site-specific mutagenesis (IFNGR1-C122A cells) were both infected with Pg, and the changes in palmitoylation of IFNGR1-C122A were analyzed using immunofluorescence and Click-iT assays. The changes in proliferation, migration and invasion ability of the infected cells were evaluated using plate cloning assay, scratch assay and Transwell assay, and IFNGR1 co-localization with lysosomal marker LAMP2 was dected using immunofluorescence assay. Immunohistochemistry was used to detect Pg infection and IFNGR1 protein expression in 50 ESCC tissues, and their correlation with the clinicopathological characteristics and survival outcomes of the patients was analyzed.@*RESULTS@#Pg infection down-regulated the protein expression of IFNGR1 in ESCC and promoted IFNGR1 palmitoylation at site 122. In IFNGR1-WT cells, Pg infection significantly enhanced cell proliferation, migration and invasion (P < 0.05). Similarly, Pg also significantly promoted proliferation, migration and invasion of IFNGR1-C122A cells, but to a lesser extent as compared with the wild-type cells (P < 0.05). Immunofluorescence assay showed that Pg and ZDHHC3 promoted IFNGR1 degradation within the lysosome. Immunohistochemical studies of the ESCC tissue samples showed a negative correlation between IFNGR1 and Pg expression, and a reduced IFNGR1 expression was correlated with a poorer survival outcome of the patient.@*CONCLUSION@#Pg infection enhances IFNGR1 palmitoylation to promote progression of ESCC, and elimination of Pg and inhibiting IFNGR1 palmitoylation may effectively control ESCC progression.

Prediction of microvascular invasion in hepatocellular carcinoma with magnetic resonance imaging using models combining deep attention mechanism with clinical features / 南方医科大学学报

OBJECTIVE@#To investigate the consistency and diagnostic performance of magnetic resonance imaging (MRI) for detecting microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and the validity of deep learning attention mechanisms and clinical features for MVI grade prediction.@*METHODS@#This retrospective study was conducted among 158 patients with HCC treated in Shunde Hospital Affiliated to Southern Medical University between January, 2017 and February, 2020. The imaging data and clinical data of the patients were collected to establish single sequence deep learning models and fusion models based on the EfficientNetB0 and attention modules. The imaging data included conventional MRI sequences (T1WI, T2WI, and DWI), enhanced MRI sequences (AP, PP, EP, and HBP) and synthesized MRI sequences (T1mapping-pre and T1mapping-20 min), and the high-risk areas of MVI were visualized using deep learning visualization techniques.@*RESULTS@#The fusion model based on T1mapping-20min sequence and clinical features outperformed other fusion models with an accuracy of 0.8376, a sensitivity of 0.8378, a specificity of 0.8702, and an AUC of 0.8501 for detecting MVI. The deep fusion models were also capable of displaying the high-risk areas of MVI.@*CONCLUSION@#The fusion models based on multiple MRI sequences can effectively detect MVI in patients with HCC, demonstrating the validity of deep learning algorithm that combines attention mechanism and clinical features for MVI grade prediction.

S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.@*METHODS@#Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.@*RESULTS@#The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).@*CONCLUSION@#S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.

Mechanism of miR-186-5p Regulating PRKAA2 to Promote Ferroptosis in Lung Adenocarcinoma Cells / 中国肺癌杂志

BACKGROUND@#Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer, and any change of miRNAs expression will affect the degree of target regulation, thus affecting intracellular homeostasis. This study verified that miR-186-5p could inhibit the proliferation, migration and invasion of LUAD cells by regulating PRKAA2.@*METHODS@#Previous investigations found that the expression of miR-186-5p was markedly suppressed in LUAD. Bioinformatics method is used to predict the target protein related to ferroptosis downstream and inquire about its expression level in LUAD and its influence on the survival of patients. Double luciferase verified the binding site of PRKAA2 and miR-186-5p. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of PRKAA2. The effects of miR-186-5p of LUAD cells as well as the mechanism by which miR-186-5p inhibits Fer-1's sensitivity to ferroptosis were confirmed by EdU, Transwell, and scratch assays. The effect of miR-186-5p on the amount of reactive oxygen species (ROS) in LUAD cells was discovered using ROS experiment. Malondialdehyde (MDA) and glutathione (GSH) experiments were used to detect the effects of miR-186-5p and PRKAA2 on ferroptosis index of LUAD cells. The concentration of lipid ROS (L-ROS) in LUAD cells were measured using the L-ROS tests to determine the effects of miR-186-5p and PRKAA2.@*RESULTS@#The expression of PRKAA2 is up-regulated, and a high level of PRKAA2 expression was associated with a poor prognosis for patients with LUAD. Overexpression of miR-186-5p decreased the gene and protein expression of PRKAA2. By promoting ferroptosis, miR-186-5p overexpression prevented lung cancer cells from proliferating, invading, and migrating. ROS could be produced in higher amounts in LUAD cells due to miR-186-5p. Overexpression of miR-186-5p and knockdown PRKAA2 up-regulated MDA content and reduced GSH content in LUAD cells, respectively. miR-186-5p could increase the content of L-ROS and promote the ferroptosis sensitivity of LUAD cells by targeting PRKAA2.@*CONCLUSIONS@#miR-186-5p promotes ferroptosis of LUAD cells through targeted regulation of PRKAA2, thus inhibiting the proliferation, invasion and migration of LUAD.
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Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion / 中华肿瘤杂志

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Effects and Mechanism of LASP1 on Proliferation, Migration, and Apoptosis of Human Colorectal Cancer LOVO Cells / 肿瘤防治研究

Objective To explore the effects and mechanism of LASP1 gene expression on the proliferation, migration, and invasion of human colorectal cancer (LOVO) cells. Methods LASP1 overexpression plasmids and LASP1 interference plasmids were constructed and transfected to LOVO cells. qRT-PCR was used to detect LASP1 mRNA expression and validate the transfection. MTT method and Tunel staining were used to detect cell proliferation and apoptosis, respectively, and scratch test and Transwell test were employed to determine the migration and invasion abilities of cells. Western blot was applied to analyze the expression of LASP1, p-FAK/FAK, and p-AKT/AKT protein in cells. Results The plasmids were successfully transfected. LASP1 overexpression increased the proliferation, migration, and invasion of LOVO cells, decreased the apoptosis, and increased LASP1, p-FAK/FAK, p-AKT/AKT protein expression (P < 0.01). LASP1 knockdown reduced the proliferation, migration, and invasion of LOVO cells, increased the apoptosis, and decreased LASP1, p-FAK/FAK, and p-AKT/AKT protein expression (P < 0.01). Conclusion LASP1 positively regulates the FAK/AKT signaling pathway to promote the proliferation, migration, and invasion of LOVO cells.

Mechanism of Cryptotanshinone Inhibiting Proliferation of Human Breast Cancer MCF7 Cells / 肿瘤防治研究

Objective To investigate the inhibitory effect of cryptotanshinone (CPT) on human breast cancer cell MCF7 and its mechanism. Methods The survival rate of MCF7 cells was measured by MTT assay. Cell apoptosis was detected by Annexin V/PI assay and Hoechst 33258 fluorescence staining assay. Cell cycle and reactive oxygen species were detected by flow cytometry. Cell migration and invasion were detected by cell scratch test and Transwell chamber test. The surface molecules CD44 and CD24 were detected by flow cytometry and microsphere culture. The expression of cell-associated proteins was detected by Western blot. Results CPT inhibited the proliferation of MCF7 cells in a dose-dependent manner, and the 24 h IC50 value was 19.24 μmol/L. Compared with the untreated group, the CPT-treated group showed cell cycle arrested in the S phase, and apoptosis was induced. The results of the cell scratch and Transwell chamber tests showed that CPT significantly inhibited the migration and invasion of MCF7 cells. Furthermore, CPT reduced the CD24-/LowCD44+ cell population in MCF7 cell-derived microspheres. Western blot results showed that CPT could up-regulate the expression of Bax protein, down-regulate the expression of BCL-2, PI3K-p85, Akt, N-cadherin, Twist1, Sox2, Oct4, and Nanog protein, effectively inhibit the phosphorylation of ER-α, and decrease the expression of ABCG2. Conclusion CPT can inhibit the proliferation of MCF7 cells by inhibiting the migration and invasion of MCF7 cells, decreasing the number of CD24-/lowCD44+ cells and affecting the expression of tumor stem cell-related proteins.