Reduced expression of microRNA-129 (miR-129) has been reported in several types of tumor cell lines as well as in primary tumor tissues. However, little is known about how miR-129 affects cell proliferation in gastric cancer. Here, we show that all miR-129 family members, miR-129-1-3p, miR-129-2-3p, and miR-129-5p, are down-regulated in gastric cancer cell lines compared with normal gastric epithelial cells. Furthermore, using the real-time cell analyzer assay to observe the growth effects of miR-129 on gastric cancer cells, we found that all three mature products of miR-129 showed tumor suppressor activities. To elucidate the molecular mechanisms underlying down-regulation of miR-129 in gastric cancer, we analyzed the effects of miR-129 mimics on the cell cycle. We found that increased miR-129 levels in gastric cancer cells resulted in significant G0/G1 phase arrest. Interestingly, we showed that cyclin dependent kinase 6 (CDK6), a cell cycle-associated protein involved in G1-S transition, was a target of miR-129. We also found that expression of the sex determining region Y-box 4 (SOX4) was inversely associated with that of miR-129-2-3p and miR-129-5p but not of miR-129-1-3p. Together, our data indicate that all miR-129 family members, not only miR-129-5p, as previously thought, play an important role in regulating cell proliferation in gastric cancer.
Keywords: CDK6; Cell cycle; Cell growth; Ct; FRA7H; Gastric cancer; MicroRNA-129; NC; PBS; PI; RB1; RPMI 1640; RT; RTCA; Roswell Park Memorial Institute 1640; SOX4; SPSS; SRY; Statistical Product and Service Solutions; TGF β; Tumor suppressor; UTR; cyclin dependent kinase 6; fragile site on human chromosome 7; miRNAs; microRNAs; negative control; phosphate buffered saline; propidium iodide; real-time cell analysis; retinoblastoma 1; reverse transcription; sex determining region Y-box 4; sex-determining region Y; threshold cycle; transforming growth factor β; untranslated region.
© 2013.