MiR-671-5p sponging activity of circMMP1 promotes esophageal squamous cancer progression.

BACKGROUND: The aim of this study was to explore the function and mechanism of circular RNA (circRNA) matrix metallopeptidase 1 (circMMP1) in the progression of esophageal squamous cell carcinoma (ESCC). METHODS: CircMMP1 expression was detected by quantitative real-time PCR (qRT-PCR), and its relationship with the prognosis of ESCC patients was evaluated by Kaplan-Meier analysis. Cells were transfected using corresponding plasmids, and the cell proliferation activity, migration and invasion capabilities in vitro were assessed. The protein level in tissues and cells was analyzed using western blotting. RNA pulldown, dual-luciferase reporter assay and RNA immunoprecipitation assay were performed in ESCC cells to detect the interaction between circMMP1 and miR-671-5p, or the correlation between miR-671-5p and ANO1. Xenograft tumor experiment was carried out to uncover the function of circMMP1 in vivo. RESULTS: The high level of circMMP1 in tumor tissues was associated with poor prognoses of ESCC patients. Knockdown of circMMP1 suppressed ESCC cell proliferation, migration and invasion in vitro. MiR-671-5p was the target of circMMP1 and mediated the inhibition effect of circMMP1 on ESCC cells. CircMMP1 targeted miR-671-5p to regulate ANO1 expression, which was downstream of miR-671-5p. Overexpression of ANO1 weakened tumor-repressive function of circMMP1 knockdown in ESCC cells. Moreover, silencing of circMMP1 impeded ESCC tumor growth in vivo. CONCLUSION: Our study provided novel evidence that circMMP1 accelerated ESCC progression by acting as a miR-671-5p sponge to enhance ANO1 expression.

A method for selecting reference beam model of VMAT plans with three 6MV beam-matched linear accelerators during radiation oncology.

Our objective was to provide a method for selecting reference beam model and evaluating the dosimetric accuracy of volumetric modulated arc therapy (VMAT) plans delivered on three Elekta beam-matched linacs during radiation oncology. Beam data was measured on three beam-matched linacs including Synergy1, Synergy2 and VersaHD. For eighteen lung and esophagus cases, fifty-four plans were generated using VMAT technique with three linac beam models respectively for point dose measurement and three-dimensional dose measurement. Each VMAT plan was executed sequentially on three linacs respectively. Measurement results were compared with treatment planning system (TPS) calculation results for all VMAT plans. Among three beam-matched linacs, discrepancy in beam output factor, percentage depth dose at 5 cm, 10 cm, 20 cm depth and MLC leaf offset are all within 1% except 20 × 20 cm2 and 30 × 30 cm2 field sizes, and discrepancy in beam profile is all within 2%. With comparison between measurement result and TPS calculation result, the absolute dose deviations are within the range of ± 3%, and the gamma passing rates are all over 95% for all VMAT plans, which are within the tolerance of clinical acceptability. Compared with all plans delivered on Synegy1 and VersaHD, the point dose discrepancy between measured results and TPS calculated results for plans delivered on Synergy2 is smallest, and the gamma passing rate between measured results and TPS calculated results for plans delivered on Synergy2 is highest. The beam-matched linacs demonstrate good agreement between measurement result and TPS calculation result for VMAT plans. The method can be used for selecting reference beam model for VMAT plans.

CDKL3 Promotes Non-small Cell Lung Cancer by Suppressing Autophagy Via Activation of PI3K/Akt/mTOR Pathway.

This study aimed to assess the role of cyclin-dependent kinase-like 3 (CDKL3) in the progression of non-small cell lung cancer (NSCLC) as well as the underlying mechanisms. Western blot and qRT-PCR were utilized to analyze CDKL3 expression in 30 pairs of NSCLC and paraneoplastic tissues. A549 cells with CDKL3 knockdown and PC9 cells with CDKL3 overexpression were constructed by infecting cells with lentiviruses expressing shRNA of CDKL3 and expressing a full-length CDKL3 mRNA, respectively. The CCK-8 assay, flow cytometry, wound healing assay, and Transwell assay were carried out to detect cell viability, apoptosis, migration, and invasion, respectively. Autophagosome morphology was observed by electron microscopy experiments, the expression of key components of the PI3K/Akt/mTOR pathway was examined via Western blot and their mRNA expression levels were determined. Besides, the stably infected NSCLC cells with reduced expression or overexpression of CDKL3 were inoculated into the right-back flank of mice to generate tumors. The results showed that CDKL3 expression was dramatically increased in NSCLC tissues. Moreover, CDKL3 promoted the viability and migration of NSCLC cells by suppressing autophagy in vitro and in vivo. In addition, CDKL3 might modulate PI3K/Akt/mTOR signaling in NSCLC. Overall, CDKL3 might promote NSCLC cell viability and metastasis by inhibiting autophagy and activating the PI3K/Akt/mTOR signaling pathway.

A novel self-assemble peptide drug design of AKT1 for anaplastic thyroid cancer therapy.

Anaplastic thyroid cancer (ATC) is an undifferentiated subtype of thyroid cancer with a markedly poor survival prognosis, estimated to occur 3-5 months after diagnosis. Akt activation is reportedly involved in tumorigenesis during ATC and represents a new therapeutic target. Based on the Akt1/bisubstrate complex structure and artificial intelligence-assisted peptide drug screening, we designed a self-assemble Akt1-targeting peptide drug exhibiting a 0.89-nm structure and potential killing ability in ATC cells. The developed self-assemble Akt1-targeting peptide drug presented IC50 values of 18.2 µM and 12.4 µM in 8303C and 8505C cells, respectively, after 72 h of incubation.

Association between G-protein coupled receptor 4 expression and microvessel density, clinicopathological characteristics and survival in hepatocellular carcinoma.

G-protein coupled receptor 4 (GPR4) acts as a proton-sensing receptor and plays a role in regulating angiogenesis. Endoglin/CD105 is a marker of cell proliferation in vascular endothelial cells, particularly in tumor vasculature cells. Although there have been several studies investigating angiogenesis in hepatocellular carcinoma (HCC), none have investigated the association between GPR4 and microvessel density (MVD)-CD105 in this type of cancer. In the present study, CD105 and GPR4 were found to be expressed in benign and malignant liver tissues by immunofluorescence staining and laser confocal microscopy. Compared with levels in benign tissues, CD105 and GPR4 were highly expressed in neoplastic tissues. Furthermore, the average fluorescence intensity of GPR4 and MVD-CD105 was positively correlated. GPR4 and CD105 were found to be co-localized in the vascular endothelium in tumor tissues. Furthermore, the expression of GPR4 was higher in the marginal region of tumor tissues compared with the central region. These findings suggest that the expression of GPR4 in tumor microvessels in HCC may be implicated in tumor angiogenesis and development. Furthermore, the association between the expression of GPR4 and the clinicopathological features of patients with HCC further suggests a role for GPR4 in tumor angiogenesis and growth. Overall, these results suggest the potential of GPR4 as a prognostic factor and as an antiangiogenic target in patients with HCC.

Overexpression of TRIM26 suppresses the proliferation, metastasis, and glycolysis in papillary thyroid carcinoma cells.

Papillary thyroid carcinoma (PTC) is the common subtype of thyroid cancer, which is a common endocrine malignancy. Tripartite motif 26 (TRIM26) has been found to act as a tumor suppressor in several cancers. However, the functional roles of TRIM26 in PTC remain unknown. In this study, we examined the TRIM26 expression in PTC and evaluated the effects of TRIM26 on proliferation, metastasis, and glycolysis in PTC cells. The results proved that TRIM26 was significantly downregulated in PTC tissues and cell lines. TRIM26 overexpression inhibited cell proliferation, migration, and invasion in PTC cells. TRIM26 overexpression also suppressed the epithelial-to-mesenchymal transition process. Besides, overexpression of TRIM26 caused significant decrease in glucose uptake and lactate production in PTC cells. Further investigations revealed that TRIM26 overexpression inhibited the activation of PI3K/Akt pathway. Treatment with an activator (740Y-P) of the PI3K/AKT pathway reversed the antitumor effects of TRIM26 on PTC cells. These findings provided evidence that TRIM26 acted as a tumor suppressor in PTC.

A Comprehensive Meta-Analysis of Association between EGFR Mutation Status and Brain Metastases in NSCLC.

Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have different clinicopathological characteristics compared with EGFR wild type NSCLC. A growing number of studies focused on the relevance between EGFR mutation status and brain metastases (BM) in NSCLC, but it remains controversial. Therefore, this study performed a comprehensive meta-analysis to untangle this issue. Several electronic databases including Pubmed, Embase, Web of science and Cochrane database were thoroughly searched. The odds ratio (OR) with 95% confidence interval (95%CI) was pooled to evaluate the relevance. Meta-regression analysis and subgroup analysis were conducted according to the heterogeneity. A total of 26 studies were identified finally in this meta-analysis. The overall OR was 1.58 (95%CI: 1.36-1.84), which indicated that EGFR mutation had a positive association with BM of NSCLC. The subgroup analysis resulted from eleven studies with lung adenocarcinoma revealed a higher possibility of BM in NSCLC with EGFR mutation compared with EGFR wild (p < 0.05). There was no significant difference in the risk of BM between NSCLC EGFR exon 19 mutation and exon 21 point mutation (p = 0.23). This meta-analysis suggests that EGFR mutation can be a risk factor for BM in NSCLC.

Pristimerin enhances the effect of cisplatin by inhibiting the miR­23a/Akt/GSK3ß signaling pathway and suppressing autophagy in lung cancer cells.

Lung cancer is a common type of cancer with a high mortality rate in China. Cisplatin (Cis) is one of the most effective broad­spectrum chemotherapeutic drugs for the treatment of advanced lung cancer. However, Cis resistance remains an obstacle in the treatment of advanced lung cancer. Pristimerin (Pris), a naturally occurring triterpenoid quinone compound, not only possesses anticancer properties, but also enhances chemosensitivity. Therefore, the present study aimed to investigate whether Pris can enhance the chemosensitivity of lung cancer cells to Cis and identify the underlying mechanism. A Cell Counting kit­8 and flow cytometry were used to determine cell viability, cell cycle progression and apoptosis in A549 and NCI­H446 cells. Western blotting was used to determine cell apoptosis­related, cell cycle­related and autophagy­related proteins. The results showed that Pris inhibited cell proliferation, and induced G0/G1 arrest and cell apoptosis in A549 and NCI­H446 cells. The western blotting revealed that Pris effectively synergized with Cis to induce cell apoptosis by inhibiting the microRNA­23a/Akt/glycogen synthase kinase 3ß signaling pathway and suppressing autophagy. In vivo xenograft experiments confirmed that Pris effectively synergized with Cis to suppress tumor growth. Collectively, these results indicate that Pris synergized with Cis and that this may be a potential therapeutic strategy to overcome lung cancer.