Abstract
MiRNAs play important roles in tumorigenesis. This study focused on exploring the effects and regulation mechanism of miRNA-137 on the biological behaviors of gastric cancer. Total RNA was extracted from tissues of 100 patients with gastric cancer and from four gastric cancer cell lines. Expression of miR-137 was detected by real-time PCR from 100 patients. The effects of miR-137 overexpression on gastric cancer cells’ proliferation, apoptosis, migration and invasion ability were investigated in vitro and in vivo. The target gene of miR-137 was predicted by Targetscan on line software, screened by dual luciferase reporter gene assay and demonstrated by western blot. As a result, the expression of miR-137 was significant reduced in gastric cancer cell line HGC-27, HGC-803, SGC-7901 and MKN-45 as well as in gastric cancer tissues compared with GES-1 cell or matched adjacent non-neoplastic tissues (p<0.001). The re-introduction of miR-137 into gastric cancer cells was able to inhibit cell proliferation, migration and invasion. The in vivo experiments demonstrated that the miR-137 overexpression can reduce the gastric cancer cell proliferation and metastasis. Bioinformatic and western blot analysis indicated that the miR-137 acted as tumor suppressor roles on gastric cancer cells through targeting AKT2 and further affecting the Bad and GSK-3β. In conclusion, the miR-137 which is frequently down-regulated in gastric cancer is potentially involved in gastric cancer tumorigenesis and metastasis by regulating AKT2 related signal pathways.
Highlights
Gastric cancer (GC) is the second frequent cause of death from cancer in the world [1]
We found some other functions of miR-137 in GC as well as another path way by which miR-137 played a role of tumor suppressor in GC tumorigenesis
We first examined the expression of mature miR-137 in 4 human gastric cancer cell lines (HGC-27, SGC-7901, SGC-7901 and MKN-45) and gastric epithelial cell (GES-1)
Summary
Gastric cancer (GC) is the second frequent cause of death from cancer in the world [1]. The mechanism of gastric carcinogenesis is largely unknown. The researchers have tried to study GC from the view of biochemistry and molecular biology that some tumor suppressor genes and tumor-related genes have been reported in GC. MicroRNAs (miRNAs) are endogenously small non-coding RNAs of 18~22 nucleotides that have been identified as posttranscriptional regulators of gene expression [2, 3]. MiRNAs play critical roles in lots of biological. PLOS ONE | DOI:10.1371/journal.pone.0130124 June 23, 2015
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