MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis.

Autor: Wu, Jian-Guo, Wang, Jin-Jie, Jiang, Xin, Lan, Jian-Ping, He, Xu-Jun, Wang, Hui-Ju, Ma, Ying-Yu, Xia, Ying-Jie, Ru, Guo-Qing, Ma, Jie, Zhao, Zhong-Sheng, Zhou, Ren
Předmět:
Zdroj: Gastric Cancer; Oct2015, Vol. 18 Issue 4, p729-739, 11p
Abstrakt: Background: MiR-125b functions as an oncogene in many cancers; however, its clinical significance and molecular mechanism in gastric cancers have never been sufficiently investigated. Here, we elucidated the functions and molecular regulated pathway s of MiR-125b in gastric cancer. Methods: We investigated MiR-125b expression in fresh tissues from 50 gastric cancer patients and 6 gastric cancer cell lines using RT-PCR, and explored its prognostic value by hybridizing MiR-125b in situ for 300 clinical gastric tumor tissues with pathological diagnosis and clinical parameters. The effects of MiR-125b on gastric cancer cells and downstream target genes and proteins were analyzed by MTT, transwell assay, RT-PCR, and western blot on the basis of silencing MiR-125b in vitro. Luciferase reporter plasmid was constructed to demonstrate MiR-125b's direct target. Results: MiR-125b was upregulated in gastric cancer tissues and cell lines, and significantly promoted cellular proliferation, migration, and invasion by downregulating the expression of PPP1CA and upregulating Rb phosphorylation. MiR-125b expression was significantly correlated with tumor size and depth of invasion, lymph nodes, distant metastasis, and TNM stage. The high-MiR-125b-expression group had a significantly poorer prognosis than the low-expression group ( P < 0.05) in stages I, II, and III, and the 5-year survival rate in of the high-expression group was significantly lower than that of the low-expression group. Conclusions: MiR-125b functions as an oncogene by targeting downregulated PPP1CA and upregulated Rb phosphorylation in gastric cancer. MiR-125b not only promotes cellular proliferation, migration, and invasion in vitro, but also acts as an independent prognostic factor in gastric cancer. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index