Upregulation of miR-153 promotes cell proliferation via downregulation of the PTEN tumor suppressor gene in human prostate cancer.
BACKGROUND
Accumulating evidence indicates that microRNAs play a pivotal role in the development and progression of prostate cancer. The present study was aimed at clarifying the biological functions of miR-153, one of the upregulated microRNAs in prostate cancers, and the signaling transduction induced by miR-153.


METHODS
miR-153 was identified to be overexpressed in prostate cancers. The probable biological function of miR-153 in cellular proliferation was then examined by diverse assays, such as MTT, colony formation and BrdUrd incorporation assay. Moreover, real-time PCR and western blotting analysis were applied to investigate the underlying molecular mechanism induced by miR-153. Luciferase assays were used to determined the FOXO1 transactivity and the direct regulation of PTEN-3'-UTR by miR-153.


RESULTS
High-throughput method identified miR-153 to be upregulated in prostate cancers, which is further confirmed by the upregulated expression in four paired prostate tumor/adjacent non-cancerous tissues from the same patients. Further studies revealed that overexpression of miR-153 promoted cell cycle transition and cell proliferation, while inhibition of miR-153 reduced this effect. Moreover, miR-153 overexpression in prostate cancer cells increased the G1/S transitional promoter, cyclin D1 expression, and decreased cyclin-dependent kinase (CDK) inhibitor, p21(Cip1) expression. In addition, we demonstrated that miR-153 directly targeted the PTEN tumor suppressor gene, activated the AKT signaling and downregulated FOXO1 transcriptional activity.


CONCLUSIONS
Taken together, our results suggest that miR-153 play an important role in promoting proliferation of human prostate cancer cells and present a novel mechanism of microRNA-mediated direct suppression of PTEN expression in prostate cancer cells.
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
Ziqing
Z
Wu
Benfu
B
He
Jincan
J
He
Xiangming
X
Mao
D020413:3' Untranslated Regions / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D020413:3' Untranslated Regions; C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C556500:MIRN153 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human