MiR-135a targets JAK2 and inhibits gastric cancer cell proliferation.
The role of tumor suppressors and cell cycle factors in gastric carcinogenesis are well understood; however, the post-transcriptional changes that affect gene expression in gastric cancer are poorly characterized. MiR-135a has been shown to play a role in Hodgkin lymphoma. The aim of this study was to investigate the expression and role of miR-135a in gastric cancer. Quantitative real-time PCR demonstrated that miR-135a expression is downregulated in the majority of human primary gastric cancer tissues (8/11; 73%), compared with pair-matched adjacent non-tumor tissues. Furthermore, compared with the nonmalignant gastric cell line, GES-1, miR-135a expression was substantially downregulated in gastric cancer cell lines of various degrees of differentiation. Target analysis indicated miR-135a directly regulates Janus kinase 2 (JAK2), a cytoplasmic tyrosine kinase involved in cytokine receptor signaling pathways. Overexpression of miR-135a significantly downregulated the expression of JAK2 protein and also reduced gastric cancer cell proliferation and colony formation in vitro. MiR-135a-mediated JAK2 downregulation also reduced p-STAT3 activation and cyclin D1 and Bcl-xL protein expression. This study suggests that miR-135a may function as a tumor suppressor via targeting JAK to repress p-STAT3 activation, reduce cyclin D1 and Bcl-xL expression and inhibit gastric cancer cell proliferation. These results imply that novel treatment approaches targeting miR-135a may potentially benefit patients with gastric cancer.
Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Hao
H
Wu
Min
M
Huang
Peng
P
Cao
Tongshan
T
Wang
Yongqian
Y
Shu
Ping
P
Liu
D000328:Adult; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D053614:Janus Kinase 2