MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1

Kuen Haur Lee, Forn Chia Lin, Tai I. Hsu, Jen Tai Lin, Jing Hong Guo, Chen Hsun Tsai, Yu Cheng Lee, Yu Chieh Lee, Chi Long Chen, Michael Hsiao, Pei Jung Lu

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Upregulation of Pin1 was shown to advance the functioning of several oncogenic pathways. It was recently shown that Pin1 is potentially an excellent prognostic marker and can also serve as a novel therapeutic target for prostate cancer. However, the molecular mechanism of Pin1 overexpression in prostate cancer is still unclear. In the present study, we showed that the mRNA expression levels of Pin1 were not correlated with Pin1 protein levels in prostate cell lines which indicated that Pin1 may be regulated at the post-transcriptional level. A key player in post-transcriptional regulation is represented by microRNAs (miRNAs) that negatively regulate expressions of protein-coding genes at the post-transcriptional level. A bioinformatics analysis revealed that miR-296-5p has a conserved binding site in the Pin1 3'-untranslated region (UTR). A luciferase reporter assay demonstrated that the seed region of miR-296-5p directly interacts with the 3'-UTR of Pin1 mRNA. Moreover, miR-296-5p expression was found to be inversely correlated with Pin1 expression in prostate cancer cell lines and prostate cancer tissues. Furthermore, restoration of miR-296-5p or the knockdown of Pin1 had the same effect on the inhibition of the ability of cell proliferation and anchorage-independent growth of prostate cancer cell lines. Our results support miR-296-5p playing a tumor-suppressive role by targeting Pin1 and implicate potential effects of miR-296-5p on the prognosis and clinical application to prostate cancer therapy.

Original languageEnglish
Pages (from-to)2055-2066
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number9
DOIs
Publication statusPublished - 2014

Fingerprint

MicroRNAs
Prostatic Neoplasms
Neoplasms
3' Untranslated Regions
Cell Line
Messenger RNA
Computational Biology
Luciferases
Prostate
Seeds
Proteins
Up-Regulation
Binding Sites
Cell Proliferation
Therapeutics
Growth

Keywords

  • MiR-296-5p
  • Pin1
  • Prostate cancer

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1. / Lee, Kuen Haur; Lin, Forn Chia; Hsu, Tai I.; Lin, Jen Tai; Guo, Jing Hong; Tsai, Chen Hsun; Lee, Yu Cheng; Lee, Yu Chieh; Chen, Chi Long; Hsiao, Michael; Lu, Pei Jung.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1843, No. 9, 2014, p. 2055-2066.

Research output: Contribution to journalArticle

Lee, Kuen Haur ; Lin, Forn Chia ; Hsu, Tai I. ; Lin, Jen Tai ; Guo, Jing Hong ; Tsai, Chen Hsun ; Lee, Yu Cheng ; Lee, Yu Chieh ; Chen, Chi Long ; Hsiao, Michael ; Lu, Pei Jung. / MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2014 ; Vol. 1843, No. 9. pp. 2055-2066.
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