MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3.
Increasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to tumorigenesis. microRNA-125b (miR-125b) was implicated to have close relationship with cell proliferation and differentiation, and downregulation of miR-125b was observed in various types of cancers. However, the biological function of miR-125b in bladder tumorigenesis is still unknown. In our study, we showed that the expression of miR-125b was significantly decreased in bladder cancer tissues and four bladder cancer cell lines. Moreover, miR-125b could suppress bladder cancer cells to form colonies in vitro and to develop tumors in nude mice. E2F3, which was critical for G1/S transition and was overexpressed in most of poor-differentiated bladder cancers, was identified as a target of miR-125b by luciferase assay. The E2F3 mRNA and protein expression levels were detected in bladder cancer tissues and cell lines, and interestingly, inverse correlations between miR-125b and E2F3 protein level were found in bladder cancer tissues and four E2F3 nonamplified cell lines. Introduction of miR-125b could reduce the expression of E2F3 protein but not the E2F3 mRNA. In addition, we observed that transfection of miR-125b could inhibit the expression of Cyclin A2, one of the E2Fs-responsive genes involved in G1/S transition. These results suggest that miR-125b may regulate G1/S transition through the E2F3-Cyclin A2 signaling pathway. Taken together, miR-125b may act as a tumor suppressor in bladder urothelium, and downregulation of miR-125b may contribute to the tumorigenesis of bladder cancer.
Huang
Li
L
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Luo
Junhua
J
Cai
Qingqing
Q
Pan
Qiuhui
Q
Zeng
Hong
H
Guo
Zhenghui
Z
Dong
Wen
W
Huang
Jian
J
Lin
Tianxin
T
D000328:Adult; D000368:Aged; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002453:Cell Cycle; D049109:Cell Proliferation; D056751:Cyclin A2 / Q000378:metabolism; D015536:Down-Regulation; D050699:E2F3 Transcription Factor / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
D056751:Cyclin A2; D050699:E2F3 Transcription Factor; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases