miR-363 promotes proliferation and chemo-resistance of human gastric cancer via targeting of FBW7 ubiquitin ligase expression

Abstract

Dysregulation of microRNA expression is involved in several pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of miR-363 in the progression and chemoresistance of gastric cancer remain enigmatic. In this study, we validated that miR-363 expression was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identifies high levels of miR-363 expression as an independent predictor for postoperative recurrence and lower overall survival. Increased miR-363 expression promotes gastric cancer cell proliferation and chemo-resistance through directly targeting the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7). Clinically, our data reveal that overexpression of miR-363 correlates with the poor survival outcomes in patients with gastric cancer, and docetaxel + cisplatin + 5-FU (DCF) regimen response is impaired in patients with miR-363 overexpression. These data suggest that miR-363 may be a potential therapeutic target for gastric cancer and serve as a biomarker for predicting response to DCF regimen treatment.

Downregulation of leucine‐rich repeats and immunoglobulin‐like domains 1 by microRNA‐20a modulates gastric cancer multidrug resistance

“…Accumulating evidence indicates that miRNA play important roles in the MDR of various cancers. miRNA, including miR‐27a, miR‐497, miR‐363, miR‐181b, miR‐15b and miR‐16, have been reported to be implicated in the MDR of GC . Our previous studies identified 11 miRNA, which regulate MDR in GC, using high‐throughput functional screening, and further confirmed that miR‐27b/CCNG1/P53/miR‐508‐5p axis plays important roles in GC‐associated MDR .…”

miR-363 inhibits the growth, migration and invasion of hepatocellular carcinoma cells by regulating E2F3

“…Chen et al demonstrated that overexpression of miR-363 in prostate cancer cells through transfection induced cell proliferation and positively regulated cell transformation property as well as promoted EMT in PC-3 cells by regulating c-myc (25). Zhang et al found that miR-363 overexpression promoted gastric cancer cell proliferation and chemoresistance by directly targeting the tumor suppressor F-box and WD repeat domain-containing 7 (FbW7) (13). In regards to HCC, the previous study showed that miR-363 inhibited cell proliferation by downregulating the expression of S1PR (16), and decreased cisplatin resistance of HCC cell, partly by targeting Mcl-1 (17).…”

“…The aberrant expression of microRNA-363 (miR-363) and its role in tumor pathogenesis and progression have already been reported in gallbladder (11), colorectal (12), gastric (13), and head and neck (14), as well as in breast cancer (15). In HCC, miR-363 expression was found to be downregulated and inhibited cell proliferation by downregulating the expression of S1PR (16), and decreased the cisplatin resistance of HCC cells, partly by targeting Mcl-1 (17).…”

MicroRNA-379 inhibits metastasis and epithelial-mesenchymal transition via targeting FAK/AKT signaling in gastric cancer

“…MicroRNAs (miRNAs) are a group of endogenous and conserved non-coding RNAs that modulate the specific protein expression through binding to the 3'-untranslated region (3'-UTR) of target mRNAs based on sequence complementarity, and function as post-transcriptional regulators of gene expression (6,7). Increasing evidence has confirmed that miRNAs are abnormally expressed in various cancers, including GC (8), and participate in different biological progress including cell growth, apoptosis, differentiation and metastasis (9,10). Therefore, miRNAs have been proposed as promising prognostic markers for GC patients (11).…”