TY - JOUR
T1 - MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2
AU - Guan, Hao
AU - Li, Weiming
AU - Li, Yuanyuan
AU - Wang, Jichang
AU - Li, Yan
AU - Tang, Yanan
AU - Lu, Shaoying
N1 - Publisher Copyright:
© 2017 Guan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/12
Y1 - 2017/12
N2 - MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo. We further identified that tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore, knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in gastric cancer cells with that transfected with miR-93 mimics. Our findings indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and therapeutic target for treatment of gastric cancer.
AB - MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo. We further identified that tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore, knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in gastric cancer cells with that transfected with miR-93 mimics. Our findings indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and therapeutic target for treatment of gastric cancer.
UR - https://www.scopus.com/pages/publications/85037680601
U2 - 10.1371/journal.pone.0189490
DO - 10.1371/journal.pone.0189490
M3 - 文章
C2 - 29220395
AN - SCOPUS:85037680601
SN - 1932-6203
VL - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e0189490
ER -
可持续发展目标 3 良好健康与福祉