Growth inhibitory effects of three miR-129 family members on gastric cancer.
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.
Department of Biochemistry and Molecular Biology, and Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.
Xiuchong
X
Yu
Haojun
H
Song
Tian
T
Xia
Shuang
S
Han
Bingxiu
B
Xiao
Lin
L
Luo
Yang
Y
Xi
Junming
J
Guo
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D018716:Molecular Mimicry; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
D035683:MicroRNAs; C541915:Mirn129 microRNA, human; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6
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