Long Noncoding RNA KLF3-AS1 Acts as an Endogenous RNA of miR-223 to Attenuate Gastric Cancer Progression and Chemoresistance.

Gastric cancer is a deadly disease, and the low rate of early diagnosis and chemoresistance largely contributed to the poor prognosis of gastric cancer. LncRNAs have been extensively reported for their roles in regulating cancer progression. In this study, we found that KLF3-AS1 was down-regulated in gastric cancer cells. Overexpression of KLF3-AS1 repressed gastric cancer cell proliferation, growth. In addition, KLF3-AS1 overexpression also exerted inhibitory effects on the gastric cancer cell invasion, migration and EMT, but promoted chemosensitivity of gastric cancer cells to cisplatin. The mechanistic studies showed that KLF3-AS1 could act as the "sponge" for miR-223 and to repress miR-223 expression in gastric cancer cells. Overexpression of miR-223 reversed the inhibitory effects of KLF3-AS1 overexpression on gastric cancer cell proliferation, invasion, migration and EMT, and attenuated the enhanced effects of KLF3-AS1 overexpression on gastric cancer cell chemosensitivity to cisplatin. The in vivo studies showed that KLF3-AS1 overexpression suppressed the tumor growth of SGC-7901 in the nude mice. In conclusion, our results for the first time demonstrated that KLF3-AS1 was down-regulated in gastric cancer cells and repressed gastric cancer cell proliferation, invasion, migration and EMT, and enhanced chemosensitivity to cisplatin. Further mechanistic results indicated that KLF3-AS1 exerted its biological function in gastric cancer cells by inhibiting miR-223 expression. Future studies are still required to decipher the detailed molecular mechanisms of KLF3-AS1 in gastric cancer.

MiRNA-339 targets and regulates ZNF689 to inhibit the proliferation and invasion of gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is the most common malignant tumor of the digestive system, and its mortality rate ranks first among malignant tumors. However, the pathogenesis of GC has not yet been fully elucidated. This study found that microRNA (miRNA)-339 is abnormally expressed in GC tissues. However, the role and molecular mechanism of miRNA-339 in the occurrence and development of GC are still unclear. METHODS: Fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the expression level of miRNA-339 in GC tissues and adjacent tissues and analyze the correlation with the clinicopathological characteristics of GC patients. Cell counting kit-8 (CCK-8) and Transwell experiments detected the effect of overexpression of miRNA-339 on the proliferation, invasion, and migration of GC cells. The luciferase reporter gene detected the downstream target molecules regulated by miRNA-339, and western blot was employed to detect the effect of overexpression of miRNA-339 on the expression of ZNF689. RESULTS: The results of fluorescence qPCR showed that miRNA-339 was less expressed in GC tissues compared with adjacent tissues, and it was correlated with the patient's clinical tumor, node, metastasis (TNM) grade and lymph node metastasis. Cell function experiments showed that overexpression of miRNA-339 can significantly inhibit the proliferation, invasion, and migration of GC cells. The luciferase reporter gene showed that miRNA-339 can bind to the 3'-UTR region of ZNF689, and overexpression of miRNA-339 can significantly inhibit the expression of ZNF689 in GC cells. Overexpression of ZNF689 can significantly block the ability of overexpression of miRNA-339 to inhibit the proliferation and migration of GC cells. CONCLUSIONS: miRNA-339 inhibits the proliferation and invasion of GC cells through targeted regulation of the expression of ZNF689. In addition, the expression level of miRNA-339 can be used as a biomarker for the prognosis of GC.

circHECTD1 facilitates glutaminolysis to promote gastric cancer progression by targeting miR-1256 and activating ß-catenin/c-Myc signaling.

Circular RNAs (circRNAs) have emerged as crucial regulators of human cancers. Glutaminolysis supplies cancer cells with adequate nitrogen and carbon to replenish the tricarboxylic acid cycle, contributing to the survival and progression of tumor cells. However, the association between circRNAs and glutaminolysis remains unclear. In this study, we showed that circHECTD1 expression was markedly upregulated in gastric cancer (GC) and was associated with lymph node metastasis and American Joint Committee on Cancer stage. The circHECTD1 expression level was found to be an independent prognostic factor for GC patients. circHECTD1 knockdown inhibited GC cell glutaminolysis, proliferation, migration, and invasion, whereas circHECTD1 overexpression promoted GC progression. Dual-luciferase and RNA immunoprecipitation assays demonstrated that miR-1256 was a direct downstream target of circHECTD1. circHECTD1 targeted miR-1256 and subsequently increased the expression level of USP5. The circHECTD1/miR-1256/USP5 axis exerted its tumor-promoting effects by activating the downstream ß-catenin/c-Myc signaling pathway. In vivo mouse models further verified the oncogenic roles of circHECTD1 in GC. Our results revealed that circHECTD1 is a glutaminolysis-associated circRNA that promotes GC progression. The circHECTD1/miR-1256/USP5 axis could thus be used as a therapeutic target for GC.

The utility of long non-coding RNA ZEB1-AS1 as a prognostic biomarker in human solid tumors: A meta-analysis.

PURPOSE: This meta-analysis aims to assess the prognostic value of long non-coding RNA ZEB1-AS1 in human solid tumors. METHODS: We searched the available databases up to January 2018. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to examine the prognostic impact of ZEB1-AS1 on patient survival. RESULTS: Eight eligible studies with a total of 586 patients were enrolled. A significant association was observed between ZEB1-AS1 overexpression and poor overall survival (OS; HR = 2.195, 95% CI: 1.749-2.755) as well as unfavorable recurrence-free survival (pooled HR = 2.205, 95% CI: 1.486-3.270), and no heterogeneity was found across these studies (p = .962, I2 = 0%). Subsequent subgroup analyses showed that cancer type, sample size, follow up months, and HR estimation method did not alter the significant prognostic value of ZEB1-AS1. ZEB1-AS1 expression was indicated to be an independent prognostic factor for tumor OS (pooled HR = 2.177, 95% CI:1.545-3.069). Furthermore, we found that increased ZEB1-AS1 expression was significantly associated with tumor stage [III-IV vs. I-II: odds ratio (OR) = 1.644, 95% CI: 1.201-2.249] and lymph node metastasis (Positive vs. Negative: OR = 2.413, 95% CI: 1.504-3.873). CONCLUSION: High expression level of ZEB1-AS1 was associated with unfavorable survival outcome for cancer patients, and ZEB1-AS1 could be used as a prognostic predictor for cancers.

miR-337-3p suppresses the proliferation and invasion of hepatocellular carcinoma cells through targeting JAK2.

Accumulating evidence has indicated that microRNA (miRNA) dysregulation contributes to hepatocellular carcinoma (HCC) progression. miR-337-3p is downregulated in gastric cancer and neuroblastoma; however, its biological function and underlying mechanism in HCC remain unclear. In this study, we showed that the expression level of miR-337-3p was significantly decreased in HCC, and was associated with several clinicopathological characteristics, including tumor multiplicity, histological differentiation, and Barcelona Clinic Liver Cancer stage. Low expression level of miR-337-3p was associated with poor survival outcomes in HCC patients. Upregulation of miR-337-3p suppressed cell proliferation, migration, and invasion in HCC. Dual luciferase assay demonstrated that JAK2 was a direct downstream target of miR-337-3p. JAK2 reintroduction restored the inhibited proliferation, migration, and invasion of miR-337-3p overexpressed HCC cells. miR-337-3p functioned as a tumor suppressor to modulate the JAK2/STAT3 signaling pathway. The present findings indicate that miR-337-3p could be used as a prognostic predictor and therapeutic candidate for HCC.