Gastric Cancer

, Volume 22, Issue 2, pp 302–313 | Cite as

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

  • Jing Yan
  • Bing Yang
  • Shuye Lin
  • Rui XingEmail author
  • Youyong LuEmail author
Original Article



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.


Gastric 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

Ethics approval

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.

Animal studies

All institutional and national guidelines for the care and use of laboratory animals were followed.

Supplementary material

10120_2018_872_MOESM1_ESM.pdf (3.5 mb)
Figure S1. The effects of miR-142-5p on the expression of EMT related markers in AGS cells; Figure S2. Effects of miR-142-5p on cell proliferation and effects of CYR61 on cell migration and invasion in GC cells in vitro. (A) Left and middle, cell proliferation was remarkably inhibited in miR-142-5p-overexpressing BGC823 and SGC7901 cells respectively compared with control cells by MTT assay. Right, cell proliferation was remarkably upregulated in miR-142-5p inhibitor-transfected AGS cells compared with control cells by MTT assay. (B) Left, Western blot detected the CYR61 expression after transfecting CYR61 in the AGS cells. Middle, transwell assay showed that the migration and invasion were significantly upregulated in CYR61-overexpressing AGS cells compared with control cells. Right, the quantification results of migrated cells and invaded cells through membrane were plotted, respectively. (C, D) Left: western blot detected the CYR61 expression after transfection of shRNA for CYR61 in the BGC823 (C) and SGC7901 (D) cells. Middle: cell migration (upprer) and invasion (lower) through membrane were remarkably downregulated after downregulation of CYR61 expression in BGC823 (C) and SGC7901 (D) cells respectively compared with control cells. Right, the quantification results of migrated cells and invaded cells through membrane were plotted, respectively. ** P < 0.01, *** P < 0.001; Figure S3. The effects of CYR61 on cell proliferation, migration and invasion in GES1 cells. (A) Western blot detected the CYR61 expression after transfecting CYR61 in GES1 cells. (B) MTT assay detected the effect of CYR61 on cell proliferation. (C) Left, cell migration (upper) and invasion (lower) were remarkably upregulated in CYR61 overexpressed GES1 cells compared with control cells. Right, the quantification of migrated cells and invaded cells through membrane were plotted, respectively, * P < 0.05, ** P < 0.01 (PDF 3575 KB)
10120_2018_872_MOESM2_ESM.docx (37 kb)
Supplementary material 2 (DOCX 37 KB)


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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018

Authors and Affiliations

  1. 1.Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital and InstituteBeijingChina

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