Downregulation of miR-142-5p promotes tumor metastasis through directly regulating CYR61 expression in gastric cancer

• DOI: 10.1007/s10120-018-0872-4
• Publication Date: 2018-09-03T11:21:30Z
• Authors: Jing Yan; Bing Yang; Shuye Lin; Rui Xing; Youyong Lu
• Keywords: 0301 basic medicine; 0303 health sciences; Down-Regulation; Kaplan-Meier Estimate; Prognosis; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Stomach Neoplasms; Biomarkers, Tumor; Humans; Neoplasm Invasiveness; Wnt Signaling Pathway; Cysteine-Rich Protein 61

Recurrence is a primary cause of gastric cancer (GC)-related deaths. We reported previously that low expression of miR-142-5p could predict recurrence in GC. The present study aimed to investigate the function and mechanism of miR-142-5p in metastasis of GC.MiR-142-5p expression was detected in 101 GC samples by qRT-PCR. Its clinical significance was statistically analyzed. The roles of miR-142-5p and its candidate target gene CYR61 in metastasis were determined both in vivo and in vitro.MiR-142-5p downregulation was significantly associated with the recurrence (P = 0.031) and poor prognosis of GC (P = 0.043). MiR-142-5p inhibited cancer cell migration and invasion both in vitro and in vivo. CYR61 was identified as a novel direct target of miR-142-5p by bioinformatics analysis of target prediction and luciferase reporter assay. The re-expression and knockdown of CYR61 could, respectively, rescue the effects induced by miR-142-5p overexpression and knockdown. MiR-142-5p attenuated GC cell migration and invasion, at least partially, by inactivation of the canonical Wnt/β-catenin signaling pathway through CYR61.The newly identified miR-142-5p-CYR61-Wnt/β-catenin axis partially illustrates the molecular mechanism of GC recurrence and represents a novel prognosis biomarker for GC.