RASSF1A inhibits epithelial-mesenchymal transition of gastric cancer cells by downregulating P-JNK.

Gastric cancer (GC) is one of the most common gastrointestinal tumors. In this study, we assessed the biological role of Ras association domain family 1 isoform A (RASSF1A) in GC cells. Expressions of RASSF1A and the relationship of RASSF1A with epithelial-mesenchymal transformation (EMT)-related proteins were assessed in five cell lines using Western blot. GC cells with RASSF1A overexpression were used to study sensitivity to cisplatin, migration, invasion, and the expression of EMT-associated biomarkers. GC cells showed profound downregulation of RASSF1A expression compared with normal human gastric mucosal cells. High RASSF1A expression was associated with increased overall survival. Overexpression of RASSF1A regulates GC cells activity and the expression of EMT-associated biomarkers. RASSF1A regulates E-cadherin and Vimentin through P-JNK pathway. Our results revealed that RASSF1A can inhibit the proliferation, migration, and invasion of GC cells via E-cadherin. Our study provides insights for further research on GC.

Circ_0008285 knockdown represses tumor development by miR-384/RRM2 axis in hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Circular RNA (circRNA) has attracted extensive attention in studies related to the malignant progression of cancer, including hepatocellular carcinoma (HCC). Therefore, its molecular mechanism in HCC needs to be further explored. MATERIALS AND METHODS: The expression levels of circ_0008285, microRNA (miR)-384 and ribonucleotide reductase subunit M2 (RRM2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed using cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine assay, cell apoptosis was analyzed by flow cytometry, and cell migration and invasion were detected by transwell assay. Protein level was detected by western blot. The relationships between miR-384 and circ_0008285 or RRM2 were predicted by bioinformatics software and validated by dual luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0008285 expression is elevated to HCC tissues and cell lines. Silencing of circ_0008285 inhibited the proliferation, migration and invasion of HCC cells but accelerated cell apoptosis in vitro and impeded HCC tumorigenesis in vivo. Mechanistically, circ_0008285 directly interacted with miR-384, and miR-384 silencing attenuated the effects of circ_0008285 interference on cell proliferation, migration, invasion, and apoptosis. RRM2 was a direct target of miR-384, and RRM2 overexpression reversed the effects of miR-384 overexpression on cell proliferation, migration, invasion, and apoptosis. In addition, circ_0008285 regulated RRM2 expression by sponging miR-384. CONCLUSION: In this study, circ_0008285 could promote the malignant biological behaviors of HCC cells through miR-384/RRM2 axis and has the potential to become a therapeutic target for HCC, providing a new idea for targeted therapy of HCC.

Comprehensive analysis on the expression profile and prognostic values of Synaptotagmins (SYTs) family members and their methylation levels in gastric cancer.

Synaptotagmins (SYTs), constitute a family of 17 membrane-trafficking protein, palying crucial roles in the development and progression of human cancers. However, only very few studies have investigated the expression profile and prognostic values of SYTs family members in gastric cancer (GC). Therefore, we comprehensively evaluated the expression, methylation, prognosis and immune significance of SYTs family members through bioinformatics analysis from the online databases in GC. The expressions of SYT4, SYT9, and SYT14 were up-regulated, and negatively associated with their methylation levels in GC. Both the over-expression of SYT4, SYT9 and SYT14 and their hypomethylation levels contributed to an unsatisfactory overall survival (OS) and progression-free survival (PFS) in GC. Moreover, the low expressions of several methylation cg sites (cg02795029, cg07581146, cg15149095, cg19922137, cg25371503, cg26158959, cg02269161, cg03226737, cg08185661, cg16437728, cg22723056 and cg24678137) were significantly correlated with an unfavorable OS and PFS in GC. Furthermore, the expression of SYT4, SYT9 and SYT14 played a pivotal role in immune cells infiltration in GC. Collectively, our current finding suggested that SYT4, SYT9 and SYT14 might be potent prognostic indictors and promising immunotherapeutic targets for GC patients.

Metabolic Reprogramming in Gastric Cancer: Trojan Horse Effect.

Worldwide, gastric cancer (GC) represents the fifth most common cancer for incidence and the third leading cause of death in developed countries. Despite the development of combination chemotherapies, the survival rates of GC patients remain unsatisfactory. The reprogramming of energy metabolism is a hallmark of cancer, especially increased dependence on aerobic glycolysis. In the present review, we summarized current evidence on how metabolic reprogramming in GC targets the tumor microenvironment, modulates metabolic networks and overcomes drug resistance. Preclinical and clinical studies on the combination of metabolic reprogramming targeted agents and conventional chemotherapeutics or molecularly targeted treatments [including vascular endothelial growth factor receptor (VEGFR) and HER2] and the value of biomarkers are examined. This deeper understanding of the molecular mechanisms underlying successful pharmacological combinations is crucial in finding the best-personalized treatment regimens for cancer patients.

RASSF1A: A promising target for the diagnosis and treatment of cancer.

The Ras association domain family 1 isoform A (RASSF1A), a tumor suppressor, regulates several tumor-related signaling pathways and interferes with diverse cellular processes. RASSF1A is frequently demonstrated to be inactivated by hypermethylation in numerous types of solid cancers. It is also associated with lymph node metastasis, vascular invasion, and chemo-resistance. Therefore, reactivation of RASSF1A may be a viable strategy to block tumor progress and reverse drug resistance. In this review, we have summarized the clinical value of RASSF1A for screening, staging, and therapeutic management of human malignancies. We also highlighted the potential mechanism of RASSF1A in chemo-resistance, which may help identify novel drugs in the future.