Downregulation of miR-142-5p promotes tumor metastasis through directly regulating CYR61 expression in gastric cancer
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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.
KeywordsGastric cancer MicroRNA-142-5p Cyr61 Prognosis Metastasis
This study was supported by National Key Research and Development Program of China (2017YFC1308900), Beijing Municipal Commission of Health and Family Planning Project (PXM2018_026279_000005), National Natural Science Foundation of China (81572346, 81772502), Beijing Natural Science Foundation (7182027), National Bio-Tech 863 Program (No. 2012AA02A203), Beijing Nova Program (Z151100000315069), Beijing Talent Fund, and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201701).
Compliance with ethical standards
This study was conducted with the approval of the Institutional Ethical Standards Committee.
Conflict of interest
The authors declare that there is no conflict of interest.
Human rights statement and informed consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.
All institutional and national guidelines for the care and use of laboratory animals were followed.
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