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The miR-486-5p plays a causative role in prostate cancer through negative regulation of multiple tumor suppressor pathways.


ABSTRACT: MicroRNAs have been broadly implicated in cancer, but their exact function and mechanism in carcinogenesis remain poorly understood. Aberrant miR-486-5p expression is frequently found in human cancers. Here we showed a significant overexpression of miR-486-5p in prostate cancer compared with that in normal tissue and cells, and we proposed that altered expression of miR-486-5p in the prostate contributed to prostate cancer. Firstly, miR-486-5p inhibition expression reduced prostate cancercell proliferation, migration, and colonization in vitro and prostate tumor development in vivo. Moreover, we integrated RNA sequencing and target genes prediction, and systemically identified miR-486-5p candidate target genes. We conducted an experiment verifying that miR-486-5p drives tumorigenesis by directly targeting multiple negative regulators, which were involved in PTEN/PI3K/Akt, FOXO, and TGF-b/Smad2 signaling. Finally, we demonstrated that hypoxia-inducible factor-1a and TCF-12 are located at the miR-486-5p promoter, which stimulates the transcription of miR-486-5p itself. Collectively, our findings unveil miR-486-5p as a powerful prostate cancer driver that coordinates the activation of multiple oncogenic pathways and demonstrates some stimulators, which mediate the miR-486-5p signaling pathway and may be targeted for therapy.

SUBMITTER: Yang Y 

PROVIDER: S-EPMC5641172 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The miR-486-5p plays a causative role in prostate cancer through negative regulation of multiple tumor suppressor pathways.

Yang Yang Y   Ji Changwei C   Guo Suhan S   Su Xin X   Zhao Xiaozhi X   Zhang Shiwei S   Liu Guangxiang G   Qiu Xuefeng X   Zhang Qing Q   Guo Hongqian H   Chen Huimei H  

Oncotarget 20170824 42


MicroRNAs have been broadly implicated in cancer, but their exact function and mechanism in carcinogenesis remain poorly understood. Aberrant miR-486-5p expression is frequently found in human cancers. Here we showed a significant overexpression of miR-486-5p in prostate cancer compared with that in normal tissue and cells, and we proposed that altered expression of miR-486-5p in the prostate contributed to prostate cancer. Firstly, miR-486-5p inhibition expression reduced prostate cancercell pr  ...[more]

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