MicroRNA-616 induces androgen-independent growth of prostate cancer cells by suppressing expression of tissue factor pathway inhibitor TFPI-2

Stephanie Ma, Yuen Piu Chan, Pak Shing Kwan, Kin Wah Lee, Mingxia Yan, Kwan Ho Tang, Ming Tat Ling, Juergen R. Vielkind, Xin Yuan Guan, Kwok Wah Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

73 Citations (Scopus)


Expression of microRNA genes is profoundly altered in cancer but their role in the development of androgenindependent prostate cancer has received limited attention as yet. In this study, we report a functional impact in prostate cancer cells for overexpression of the microRNA miR-616, which occurred consistently in cells that were androgen-independent (AI) versus androgen-dependent (AD). miR-616 overexpression was confirmed in malignant prostate tissues as opposed to benign prostate specimens. Stable miR-616 overexpression in LNCaP cells by a lentiviral-based approach stimulated AI prostate cancer cell proliferation in vitro whereas concomitantly reducing androgen-induced cell growth. More importantly, miR-616 overexpressing LNCaP cells overcame castration resistance as shown by an enhanced ability to proliferate in vivo after bilateral orchiectomy. Conversely, antagonizing miR-616 in AI prostate cancer cells yielded opposite effects. Microarray profiling and bioinformatics analysis identified the tissue factor pathway inhibitor TFPI-2 mRNA as a candidate downstream target of miR-616. In support of this candidacy, we documented interactions between miR-616 and the 30UTR of TFPI-2 and determined TFPI-2 expression to be inversely correlated to miR-616 in a series of prostate cell lines and clinical specimens. Notably, reexpression of TFPI-2 in LNCaP cells with stable miR-616 overexpression rescued the AD phenotype, as shown by a restoration of androgen dependence and cell growth inhibition. Taken together, our findings define a functional involvement for miR-616 and TFPI-2 in the development and maintenance of androgen-independent prostate cancer.
Original languageEnglish
Pages (from-to)583-592
Number of pages10
JournalCancer Research
Issue number2
Publication statusPublished - 15 Jan 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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