Phellinus linteus activates Treg cells via FAK to promote M2 macrophage polarization in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor worldwide. Within HCC's tumor microenvironment, focal adhesion kinase (FAK) plays a critical role. Regulatory T cells (Treg) modulate the polarization of tumor-associated macrophages , but the relationship between FAK, Treg cells, and macrophages remains underexplored. Phellinus linteus (PL) shows promise as a treatment for HCC due to its pharmacological effects. This study aimed to explore the relationship between FAK and Treg-macrophages and to assess whether PL could exert a protective effect through the FAK process in HCC. Initially, C57BL/6-FAK-/- tumor-bearing mice were utilized to demonstrate that FAK stimulates HCC tumor development. High dosages (200 µM) of FAK and the FAK activator ZINC40099027 led to an increase in Treg (CD4+CD25+) cells, a decrease in M1 macrophages (F4/80+CD16/32+, IL-12, IL-2, iNOS), and an increase in M2 macrophages (F4/80+CD206+, IL-4, IL-10, Arg1, TGF-ß1). Additionally, FAK was found to encourage cell proliferation, migration, invasion, and epithelial-mesenchymal transition while inhibiting apoptosis in HepG2 and SMMC7721 cells. These effects were mediated by the PI3K/AKT1/Janus Kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase (p38 MAPK)/Jun N-terminal Kinase (JNK) signaling pathways. Furthermore, PL exhibited a potent antitumor effect in vivo in a dose-dependent manner, reducing FAK, Treg cells, and M2 macrophages, while increasing M1 macrophages. This effect was achieved through the inhibition of the PI3K/AKT/JAK/STAT3, and p38/JNK pathways. Overall, our findings suggest that FAK promotes HCC via Treg cells that polarize macrophages toward the M2 type through specific signaling pathways. PL, acting through FAK, could be a protective therapy against HCC.

Fenofibrate suppresses the progression of hepatoma by downregulating osteopontin through inhibiting the PI3K/AKT/Twist pathway.

Primary hepatic carcinoma (PHC) is a leading threat to cancer patients with few effective treatment strategies. OPN is found to be an oncogene in hepatocellular carcinoma (HCC) with potential as a treating target for PHC. Fenofibrate is a lipid-lowering drug with potential anti-tumor properties, which is claimed with suppressive effects on OPN expression. Our study proposes to explore the molecular mechanism of fenofibrate in inhibiting HCC. OPN was found extremely upregulated in 6 HCC cell lines, especially Hep3B cells. Hep3B and Huh7 cells were treated with 75 and 100 µM fenofibrate, while OPN-overexpressed Hep3B cells were treated with 100 µM fenofibrate. Decreased clone number, elevated apoptotic rate, reduced number of migrated cells, and shortened migration distance were observed in fenofibrate-treated Hep3B and Huh7 cells, which were markedly abolished by the overexpression of OPN. Furthermore, the facilitating effect against apoptosis and the inhibitory effect against migration of fenofibrate in Hep3B cells were abolished by 740 Y-P, an agonist of PI3K. Hep3B xenograft model was established, followed by treated with 100 mg/kg and 200 mg/kg fenofibrate, while OPN-overexpressed Hep3B xenograft was treated with 200 mg/kg fenofibrate. The tumor growth was repressed by fenofibrate, which was notably abolished by OPN overexpression. Furthermore, the inhibitory effect of fenofibrate on the PI3K/AKT/Twist pathway in Hep3B cells and Hep3B xenograft model was abrogated by OPN overexpression. Collectively, fenofibrate suppressed progression of hepatoma downregulating OPN through inhibiting the PI3K/AKT/Twist pathway.

Integrated bioinformatics analysis of noncoding RNAs with tumor immune microenvironment in gastric cancer.

In recent years, molecular and genetic research hotspots of gastric cancer have been investigated, including microRNAs, long noncoding RNAs (lncRNAs) and messenger RNA (mRNAs). The study on the role of lncRNAs may help to develop personalized treatment and identify potential prognostic biomarkers in gastric cancer. The RNA-seq and miRNA-seq data of gastric cancer were downloaded from the TCGA database. Differential analysis of RNA expression between gastric cancer samples and normal samples was performed using the edgeR package. The ceRNA regulatory network was visualized using Cytoscape. KEGG pathway analysis of mRNAs in the ceRNA network was performed using the clusterProfiler package. CIBERSORT was used to distinguish 22 immune cell types and the prognosis-related genes and immune cells were determined using Kaplan-Meier and Cox proportional hazard analyses. To estimate these nomograms, we used receiver operating characteristic and calibration curve studies. The ceRNA regulation network of gastric cancer was built in this study, and the genes in the network were analyzed for prognosis. A total of 980 lncRNAs were differentially expressed, of which 774 were upregulated and 206 were downregulated. A survival study identified 15 genes associated with gastric cancer prognosis, including VCAN-AS1, SERPINE1, AL139002.1, LINC00326, AC018781.1, C15orf54, hsa-miR-145. Monocytes and Neutrophils were associated with the survival rate of gastric cancer. Our research uncovers new ceRNA network for the detection, treatment, and monitoring of gastric cancer.

Novel Weigh-in-Motion Pavement Sensor Based on Self-Sensing Nanocomposites for Vehicle Load Identification: Development, Performance Testing, and Validation.

The development of the transportation industry has led to an increasing number of overloaded vehicles, which reduces the service life of asphalt pavements. Currently, the traditional vehicle weighing method not only involves heavy equipment but also has a low weighing efficiency. To deal with the defects in the existing vehicle weighing system, this paper developed a road-embedded piezoresistive sensor based on self-sensing nanocomposites. The sensor developed in this paper adopts an integrated casting and encapsulation technology, in which an epoxy resin/MWCNT nanocomposite is used for the functional phase, and an epoxy resin/anhydride curing system is used for the high-temperature resistant encapsulation phase. The compressive stress-resistance response characteristics of the sensor were investigated by calibration experiments with an indoor universal testing machine. In addition, the sensors were embedded in the compacted asphalt concrete to validate the applicability to the harsh environment and back-calculate the dynamic vehicle loads on the rutting slab. The results show that the response relationship between the sensor resistance signal and the load is in accordance with the GaussAmp formula. The developed sensor not only survives effectively in asphalt concrete but also enables dynamic weighing of the vehicle loads. Consequently, this study provides a new pathway to develop high-performance weigh-in-motion pavement sensors.

20-Hydroxyecdysone inhibits inflammation via SIRT6-mediated NF-κB signaling in endothelial cells.

20-Hydroxyecdysone (20E) is known to have numerous pharmacological activities and can be used to treat diabetes and cardiovascular diseases. However, the protective effects of 20E against endothelial dysfunction and its targets remain unclear. In the present study, we revealed that 20E treatment could modulate the release of the endothelium-derived vasomotor factors NO, PGI2 and ET-1 and suppress the expression of ACE in TNF-α-induced 3D-cultured HUVECs. In addition, 20E suppressed the expression of CD40 and promoted the expression of SIRT6 in TNF-α-induced 3D-cultured HUVECs. The cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and molecular docking results demonstrated that 20E binding increased SIRT6 stability, indicating that 20E directly bound to SIRT6 in HUVECs. Further investigation of the underlying mechanism showed that 20E could upregulate SIRT6 levels and that SIRT6 knockdown abolished the regulatory effect of 20E on CD40 in TNF-α-induced HUVECs, while SIRT6 overexpression further improved the effect of 20E. Moreover, we found that 20E could reduce the acetylation of NF-κB p65 (K310) through SIRT6, but the catalytic inactive mutant SIRT6 (H133Y) did not promote the deacetylation of NF-κB p65, suggesting that the inhibitory effect of 20E on NF-κB p65 was dependent on SIRT6 deacetylase activity. Additionally, our results indicated that 20E inhibited NF-κB via SIRT6, and the expression of CD40 was increased in HUVECs treated with SIRT6 siRNA and NF-κB inhibitor. In conclusion, the present study demonstrates that 20E exerts its effect through SIRT6-mediated deacetylation of NF-κB p65 (K310) to inhibit CD40 expression in ECs, and 20E may have therapeutic potential for the treatment of cardiovascular diseases.

microRNA-216a-5p inhibits the development of gastric cancer through target combination with TCTN1.

BACKGROUND: We aimed at investigating microRNA-216a-5p expression in gastric cancer (GC) tissues and further exploring whether microRNA-216a-5p suppresses GC progression through interacting with TCTN1. METHODS: microRNA-216a-5p expression in 60 pairs of GC tissues and adjacent ones was studied by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and the relationship between microRNA-216a-5p and clinical indicators as wells as prognosis of GC patients was also analyzed. At the same time, qRT-PCR was conducted to further verify microRNA-216a-5p level in GC cells. The impacts of microRNA-216a-5p on GC cell functions were evaluated using cell counting kit-8, plate cloning and Transwell experiments. Meanwhile, we studied the specific regulatory relationship between microRNA-216a-5p and TCTN1 in depth. RESULTS: Our data showed that microRNA-216a-5p level in GC tumor specimens was remarkably lower than that in adjacent ones. In comparison to patients in group of high microRNA-216a-5p expression, patients in group of low expression showed an increased metastasis incidence and a lower survival rate. Cell functional experiments suggested that microRNA-216a-5p mimics markedly attenuated the proliferative and migratory capacities of GC cells. Bioinformatics analysis suggest that microRNA-216a-5p can bind to its target gene TCTN1, which was confirmed by luciferase assay. Further, qPCR results revealed a negative correlation between the expression of TCTN1 and microRNA-216a-5p in GC tumor tissues. Finally, in vitro cell experiments suggested that overexpression of TCTN1 could reverse the inhibitory impact of upregulation of microRNA-216a-5p on GC cell functions. CONCLUSIONS: microRNA-216a-5p, abnormally lowly expressed in GC tissues, is markedly relevant to the high metastasis incidence and the poor prognosis of GC patients; in addition, microRNA-216a-5p inhibited GC's migration and proliferation capabilities through regulating TCTN1.

Comprehensive analysis of lncRNA-mediated ceRNA networkfor hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a high-burden cancer. The molecular mechanism of HCC has not been fully elucidated. Notably, current research has revealed a significant function for long non-coding RNAs (lncRNAs) in the prognosis of patients with HCC. Here, this study aims to construct a regulated lncRNA-mediated ceRNA network and find biological targets for the treatment of HCC. Methods: Based on the RNA expression patterns from the TCGA, we did an analysis to determine which genes were expressed differently between liver tumor tissues and noncancerous tissues. Then, using bioinformatic tools, we built a lncRNA-miRNA-mRNA ceRNA network and used GO and KEGG functional analyses on the DEmRNAs connected to ceRNA networks. The main lncRNAs in the subnetwork were chosen, and we next looked at the relationships between these lncRNAs and the clinical characteristics of patients with HCC. The prognosis-related genes and immune cells were identified using Kaplan-Meier and Cox proportional hazard analyses, and CIBERSORT was utilized to separate the 22 immune cell types. CCK8 assay was performed to measure cell viability in HCC cells after lncRNA HOTTIP modulation. Results: Differentially expressed mRNA and lncRNAs in HCC and paracancerous tissues were identified. There are 245 lncRNAs, 126 miRNAs, and 1980 mRNAs that are expressed differently in liver tumour tissues than in noncancerous cells. Function analysis showed that mRNAs in ceRNA network were significantly enriched in G1/S transition of mototiv cell cycle, positive regulation of cell cycle process, hepatocellular carcinoma, and cancer related pathways. CD8 T cells and T follicular helper cells had a favourable link with a 0.65 correlation coefficient. Additionally, there was a strong correlation between Eosinophils, activated NK cells, and B memory cells. Strikingly, depletion of lncRNA HOTTIP inhibited viability of HCC cells. In addition, miR-205 upregulation suppressed viability of HCC cells, while miR-205 downregulation repressed viability of HCC cells. Notably, miR-205 depletion rescued HOTTIP depletion-mediated suppression of cell viability in HCC. Conclusion: A ceRNA network was created by examining the lncRNA, miRNA, and mRNA expression profiles of liver tumours from the TCGA database. LncRNA HOTTIP promoted cell viability via inhibition of miR-205 in HCC cells.

Association of sleep duration, sleep apnea, and shift work with risk of colorectal neoplasms: a systematic review and meta-analysis.

Background: Although studies have reported that certain sleep characteristics, such as sleep duration and sleep apnea, are linked to the risk of colorectal cancer (CRC), this link remains contentious because of the limited evidence from individual studies. Furthermore, evidence indicated that shift work involving circadian disruption as a probable human carcinogen. This systematic review and meta-analysis aimed to examine the associations between sleep duration, sleep apnea, and shift work with the risk of colorectal neoplasms, including CRC and colorectal adenoma (CRA). Methods: We conducted a comprehensive literature search in PubMed, Embase, and Web of Science databases. The inclusion criteria were determined using PICOS principles. Observational studies reporting associations of sleep duration, sleep apnea, or shift work with risk of CRC or CRA were included. We assessed the risk of bias on the basis of the Newcastle-Ottawa Scale. Results: A total of 18 observational studies were included. Of these studies, nine studies reported the effect of sleep duration on risk of colorectal neoplasms, five reported the effect of sleep apnea, and six reported the effect of shift work. The relative risk (RR) for colorectal neoplasms was 1.06 [95% confidence interval (CI): 0.94, 1.20] in the short sleep duration group compared with the moderate sleep duration group. Long sleep duration was associated with an increased risk of colorectal neoplasms (RR: 1.33, 95% CI: 1.07, 1.65). The pooled results showed that sleep apnea was associated with an increased risk of colorectal neoplasms (RR: 1.75, 95% CI: 1.56, 1.97). Furthermore, results showed that the association between shift work and the risk of colorectal neoplasms was not significant (RR: 1.06, 95% CI: 0.95, 1.17). No publication bias was observed in all the analyses (all P>0.05). The sensitivity analysis showed that no individual study substantially influenced the pooled RRs for colorectal neoplasms and CRC. Conclusions: Our findings suggest the significant positive association of long sleep duration and sleep apnea with risk of colorectal neoplasms and CRC. Given that sleep characteristics may be a potentially modifiable risk factor for colorectal neoplasms, further understanding of its role in carcinogenesis will provide valuable insight for cancer prevention.

SMYD2 aggravates gastrointestinal stromal tumor via upregulation of EZH2 and downregulation of TET1.

SMYD2, as an oncogene, has been involved in multiple types of cancer, but the potential role of SMYD2 in gastrointestinal stromal tumors (GIST) remains enigmatic and requires further investigation. Hence, this study was conducted with the main objective of analyzing the effect of SMYD2 on GIST. GIST and adjacent normal tissues were collected from 46 patients with GIST where the expression of EZH2, SMYD2, and TET1 was determined, followed by the analysis of their interactions. The functional role of SMYD2 in cell biological functions was determined using a loss-of-function assay in GIST-T1 cells. Nude mouse xenograft experiments were performed to verify the role of the SMYD2/EZH2/TET1 axis in GIST in vivo. EZH2 was upregulated in GIST tissues and cell lines, which was positively correlated with SMYD2 expression and inversely correlated with TET1 expression in GIST tissues. EZH2 silencing due to SMYD2 inhibition reduced GIST-T1 cell proliferation and accelerated cell senescence. EZH2 repressed TET1 expression by promoting H3K27me3 methylation in the TET1 promoter region. TET1 inhibition reversed the effect of EZH2 silencing on the biological functions of GIST-T1 cells. In vivo data further revealed the promoting effect of SMYD2 on the progression of GIST by regulating the EZH2/TET1 axis. Overall, this study demonstrates that SMYD2 can increase EZH2 expression while suppressing TET1 expression, thus accelerating GIST, and creating new treatment opportunities for GIST.

Artemisinin upregulates neural cell adhesion molecule L1 to attenuate neurological deficits after intracerebral hemorrhage in mice.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a subtype of stroke and results in neurological deficits in patients without any effective treatments. Artemisinin (ART), a well-known antimalarial Chinese medicine, exerts multiple essential roles in the central and peripheral nervous system due to its antioxidative and anti-inflammation properties. Neural cell adhesion molecule L1 (L1CAM, L1) is considered to be implicated in neural development, functional maintenance, and neuroprotection during disease. However, whether these two essential molecules are neuroprotective in ICH remains unclear. METHODS: Therefore, the present study investigated the influence of ART on the recovery of neurological deficits in a mouse model of ICH induced by collagenase and the underlying mechanism. RESULTS: It was revealed that ART is capable of upregulating L1 expression to alleviate brain edema, reduce oxidative stress, and inhibit inflammation to alleviate ICH-induced brain injury to improve the neurological outcome in mice suffering from ICH. CONCLUSION: These results may lay the foundation for ART to be a novel candidate treatment for ICH.

Deubiquitinase PSMD7 promotes the proliferation, invasion, and cisplatin resistance of gastric cancer cells by stabilizing RAD23B.

Ubiquitination, a crucial post-translational modification, controls substrate degradation and can be reversed by deubiquitinases (DUBs). An increasing number of studies are showing that DUBs regulate the malignant behavior and chemotherapy resistance of gastric cancer (GC) by stabilizing various proteins. However, the expression level and biological function of the DUB, proteasome 26S subunit, non-ATPase 7 (PSMD7), in GC remains unknown. Herein, we report for the first time that PSMD7 is frequently overexpressed in GC tissues. Elevated levels of PSMD7 were also detected in GC cell lines. Notably, the upregulation of PSMD7 closely correlated with malignant clinical parameters and reduced the survival of GC patients. Functionally, we found that PSMD7 knockdown consistently suppressed the proliferation, migration, and invasion of AGS and SGC-7901 cells. Ectopic expression of PSMD7 facilitated GC cell proliferation and mobility. Based on protein-protein interaction prediction, RAD23 homolog B (RAD23B) protein was identified as a candidate substrate of PSMD7. PSMD7 positively regulated the abundance of RAD23B and xeroderma pigmentosum, complementation group C (XPC) protein in GC cells. The interaction between PSMD7 and RAD23B was confirmed using protein immunoprecipitation. PSMD7 knockdown enhanced the ubiquitination and degradation of RAD23B protein in GC cells. PSMD7 promoted cell viability, apoptosis resistance, and DNA damage repair in GC cells upon cisplatin (DDP) treatment. Moreover, PSMD7 silencing inhibited tumor growth and enhanced the sensitivity of GC cells to DDP treatment in mice. In summary, PSMD7 was highly expressed in GC and contributed to the malignant behavior and DDP resistance of tumor cells by stabilizing RAD23B.

ADCK1 activates the ß-catenin/TCF signaling pathway to promote the growth and migration of colon cancer cells.

As a result of mutations in the upstream components of the Wnt/ß-catenin signaling pathway, this cascade is abnormally activated in colon cancer. Hence, identifying the activation mechanism of this pathway is an urgent need for the treatment of colon cancer. Here, we found an increase in ADCK1 (AarF domain-containing kinase 1) expression in clinical specimens of colon cancer and animal models. Upregulation of ADCK1 expression promoted the colony formation and infiltration of cancer cells. Downregulation of ADCK1 expression inhibited the colony formation and infiltration of cancer cells, in vivo tumorigenesis, migration, and organoid formation. Molecular mechanistic studies demonstrated that ADCK1 interacted with TCF4 (T-cell factor 4) to activate the ß-catenin/TCF signaling pathway. In conclusion, our research revealed the functions of ADCK1 in the development of colon cancer and provided potential therapeutic targets.

Jervine exhibits anticancer effects on nasopharyngeal carcinoma through promoting autophagic apoptosis via the blockage of Hedgehog signaling.

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the superior mucosal epithelium of the nasopharynx. However, effective therapies for NPC are still required. Reducing Hedgehog signaling pathway has been shown to suppress tumor growth. In this study, we attempted to explore whether Jervine (JV), an inhibitor of Hedgehog signaling, had anti-cancer effects on NPC, and the underlying mechanisms. Our findings showed that JV treatments markedly reduced the proliferation of NPC cells in a dose- and time-dependent manner. Cell cycle arrest in G2/M phase was significantly enhanced by JV, along with evident DNA damage. Moreover, JV treatment effectively induced apoptosis in NPC cells through improving Caspase-3 activation. Furthermore, ROS production and mitochondrial impairments were detected in JV-incubated NPC cells with elevated releases of Cyto-c from mitochondria. JV also dramatically triggered autophagy through blocking AKT/mTOR and increasing AMPK signaling pathways. Intriguingly, we showed that JV-induced apoptosis was mainly via an autophagy-dependent manner. In addition, the expression levels of SHH, PTCH1, SMO and GLI1 were markedly suppressed in NPC cells, demonstrating the hindered Hedgehog signaling. Importantly, we found that JV-induced apoptosis and autophagy were closely associated with the blockage of Hedgehog signaling. Our in vivo studies confirmed the anti-cancer effects of JV on NPC through inducing autophagy, as evidenced by the markedly reduced tumor growth rate and weight without side effects and toxicity. Taken together, JV may be a promising and effective agent for human NPC treatment through repressing Hedgehog signaling pathway and inducing autophagic cell death.

Clinical symptoms between severe and non-severe COVID-19 pneumonia: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019, (COVID-19) is a major problem in public health in the world. Up to June, 2020, the number of infections arising to 8,690,000 and cause 410,000 deaths all over the world. Identification the clinical symptoms from non-severe to severe is important for clinician. This meta-analysis aimed to compare the clinical symptoms between severe and non-severe COVID-19 pneumonia. METHODS: Electronic databases including PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure database, Wanfang Database and Chinese Biomedical Literature Database were searched from its inception to June 21, 2020. We only included severe versus non-severe COVID-19 pneumonia patients and pooled results were summarized by STATA 12.0 software.Two researchers independently selected the study and assessed the quality of the included studies. The heterogeneity was measured by I tests (I < 50 indicates little heterogeneity, I≥50 indicates high heterogeneity). Publication bias was ruled out by funnel plot and statistically assessed by Begg test (P > .05 as no publication bias). RESULTS: Results will be published in relevant peer-reviewed journals. CONCLUSION: Our study aims to systematically present the clinical symptoms between non-severe and severe of COVID-19 patients, which will be provide clinical guidance for COVID-19 patients.

BMX-ARHGAP fusion protein maintains the tumorigenicity of gastric cancer stem cells by activating the JAK/STAT3 signaling pathway.

BACKGROUND: Cancer stem cells (CSCs), drug-resistant cancer cell subsets, are known to be responsible for tumor metastasis and relapse. The JAK/STAT pathway, activated by SH2 domain, is known to regulate the tumor growth in gastric cancer (GC). Now, this study was designed to examine whether BMX-ARHGAP affects the GC stem cell properties and the underlying regulatory network via JAK/STAT axis. METHODS: BMX-ARHGAP expression was characterized in GC tissues and cells by RT-qPCR and western blot assay. When BMX-ARHGAP was overexpressed or silenced via plasmids or siRNA transfection, the stem cell properties were assessed by determining stem cell markers CD133, CD44, SOX2 and Nanog, followed by cell sphere and colony formation assays. Subsequently, cell proliferation and invasion were examined by conducting EdU and Transwell assays. The JAK/STAT3 signaling pathway activation was inhibited using AG490. ARHGAP12, BMX exon 10-11, BXM-SH2, JAK2 and STAT3 expression patterns were all determined to examine the regulatory network. The stem cell property in nude mice was also tested. RESULTS: BMX-ARHGAP was determined to be enriched in the GC. Overexpression of BMX-ARHGAP resulted in increased expression of CD133, CD44, SOX2 and Nanog protein, and accelerated proliferation and invasion of CD133+CD44+ cells as well as facilitated self-renewal potential of GC cells. However, the inhibition of the JAK/STAT3 signaling pathway reversed the stimulating effect of BMX-ARHGAP on proliferative and invasion abilities of CD133+CD44+ cells. The overexpression of BMX-ARHGAP was suggested to increase the BMX-SH2 protein expression via ARHGAP 5'UTR, and activate the JAK/STAT3 signaling pathway. Also, BMX-ARHGAP promoted tumor growth in nude mice. CONCLUSIONS: The aforementioned results demonstrated that the BMX-ARHGAP-dependent SH2 domain-JAK/STAT3 axis mediates the maintenance of GC stem cells, benefiting the development of new potential therapeutic targets for GC.

Suppression of BMX-ARHGAP fusion gene inhibits epithelial-mesenchymal transition in gastric cancer cells via RhoA-mediated blockade of JAK/STAT axis.

Gastric cancer (GC) is one of the main causes of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) is an important biological process involving the process by which malignant tumor cells obtain the ability of migration, invasion, resistance of apoptosis, and degradation in the extracellular matrix. The current study aimed at investigating whether bone marrow X kinase Rho GTPase activating protein 12 (BMX-ARHGAP) fusion gene affects GC. First, short hairpin RNA (shRNA) against BMX-ARHGAP or BMX-ARHGAP were introduced to treat SGC-7901 cells with the highest BMX-ARHGAP among the five GC cell lines (SGC-7901, MKN-45, NCI-N87, SNU-5, and AGS). Next, cell vitality, drug resistance, migration, and invasion of SGC-7901 cells, activities of Rho and JAK/STAT axis, as well as EMT and lymph node metastasis (LNM) were evaluated. The survival rate of the mice was then determined through the transfection of the specific pathogen-free NOD-SCID mice with treated SGC-7901 cells. The results showed that BMX-ARHGAP expression was associated with the infiltration degree of GC tumor and poor prognosis for patients with GC. BMX-ARHGAP silencing was found to play an inhibitory role in the Rho and JAK/STAT axis to reduce cell vitality, drug resistance, migration and invasion, reverse EMT process, as well as inhibit LNM. BMX-ARHGAP overexpression was observed to have induced effects on GC cells as opposed to those inhibited by BMX-ARHGAP silencing. The survival rate of mice was increased after transfection with silenced BMX-ARHGAP. These findings provided evidence that the suppression of BMX-ARHGAP resulted in the inhibition of RhoA to restraint the development of GC cells by blocking the JAK/STAT axis.

Neurofibroma discharged from the anus with stool: A case report and review of literature.

Isolated neurofibromas that affect the gastrointestinal tract are rare and almost always manifest as neurofibromatosis type 1 or multiple endocrine neoplasia type 2b. In this paper, we present a case of a 24-year-old female with abdominal pain who discharged a neurofibroma in her stool without any blood on it. A colonoscopy showed multiple small polyps in the sigmoid colon and a nodule in the ileocecus. The pathology results and the immunohistochemical stains of the removed neoplasm from the ileocecus confirmed the diagnosis was a bowel neurofibroma. We report a rare case of ileocecal neurofibroma due to the patient's affected gastrointestinal tract, without any associated systemic syndrome other than a neurofibroma discharged in the stool.

H2AFY is a novel fusion partner of MECOM in acute myeloid leukemia.

The MECOM gene encoding a zinc finger protein that functions as a transcription factor, was located on chromosome 3q26, and rearrangements of MECOM often cause its overexpression in acute myeloid leukemia (AML). We identified H2AFY as a novel fusion gene partner of MECOM in an elderly male AML patient with cryptic 3q26 rearrangement using the whole transcriptome sequencing, who carried out abnormal karyotype of 46,XY,t(3;5)(q27;q31),add(14)(p11). We validated the existence of the unreported H2AFY-MECOM fusion gene by RT-PCR and Sanger DNA sequencing, and detected mutations of NRAS and BCOR in this patient. In addition, we found abnormally elevated expression of MECOM in this patient by quantitative-polymerase chain reaction (RQ-PCR). Further research is needed to investigate functional characterizations of this novel fusion in the development of AML.

MiR-122-5p inhibits cell migration and invasion in gastric cancer by down-regulating DUSP4.

OBJECTIVE: To explore the relationship between miR-122-5p and DUSP4 and their effects on gastric cancer (GC) cell mobility and invasiveness. METHODS: Abnormally expressed miRNAs and mRNAs were analyzed using microarrays. The miR-122-5p and DUSP4 mRNA expression levels in GC tissues and cells were determined by RT-qPCR. The target relationship between miR-122-5p and DUSP4 was validated by dual luciferase reporter assay. GC cell mobility and invasiveness were respectively observed by wound healing assay and transwell invasion assay. Western blot and immunohistochemistry were used for detection of the expressions of DUSP4 protein and MMP2 and MMP9 proteins related to cell invasion and migration. The migration and invasion abilities of gastric cancer cells in vivo were evaluated according to the number of lung metastatic nodules in mice. RESULTS: The expression of miR-122-5p in GC tissues and cells was significantly down-regulated, whereas DUSP4 expression was up-regulated. Bioinformatics prediction strategies and dual luciferase reporter assay verified the binding sites of miR-122-5p on 3'UTR of DUSP4 and the target relationship between miR-122-5p and DUSP4. Overexpression of miR-122-5p and knockdown of DUSP4 in BGC-823 cells observantly suppressed GC cell mobility and invasiveness, whereas downregulation of miR-122-5p expression promoted cell metastasis. MiR-122-5p inhibited GC cell mobility and invasiveness and pulmonary tumor metastasis via downregulation of DUSP4. CONCLUSION: MiR-122-5p restrained migration and invasion abilities of GC cells by repressing DUSP4.

Identification of a novel gene fusion (BMX-ARHGAP) in gastric cardia adenocarcinoma.

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is one of the major causes of cancer related mortality worldwide. We aim to provide new understanding in the pathogenesis of GCA through investigations on gene expression alterations. METHODS: We preformed RNA-Seq for one pair of GCA and matched non-tumor tissues. Differentially expressed genes (DEGs) and fusion genes were acquired. PCR and gel analysis in additional 14 pairs of samples were performed to validate the chimeric transcripts. RESULTS: 1590 up-regulated and 709 down-regulated genes were detected. Functional analysis revealed that these DEGs were significantly overrepresented in gene ontology items of cell cycle, tumor invasion and proliferation. Moreover, we firstly discovered 3 fusion genes in GCA, including BMX-ARHGAP, LRP5- LITAF and CBX3-C15orf57. The chimeric transcript BMX-ARHGAP was validated and recurrently occurred in 4/15 independent tumor tissues. CONCLUSIONS: Our results may provide new understanding of GCA and biomarkers for further therapeutic studies. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_218.