title: MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1.
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.
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kuen-Haur
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan; Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Forn-Chia
authors.initials: FC
authors.lastname: Lin
authors.affiliation: Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Tai-I
authors.initials: TI
authors.lastname: Hsu
authors.affiliation: Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan; Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Jen-Tai
authors.initials: JT
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jing-Hong
authors.initials: JH
authors.lastname: Guo
authors.affiliation: Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chen-Hsun
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan; Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan. Electronic address: pjlu2190@mail.ncku.edu.tw.
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C549871:MIRN296 microRNA, human; D035683:MicroRNAs; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012333:RNA, Messenger; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase
keywords: Pin1; Prostate cancer; miR-296-5p