Loss of miR-449a in ERG-associated prostate cancer promotes the invasive phenotype by inducing SIRT1

Parameet Kumar, Shashwat Sharad, Gyorgy Petrovics, Ahmed Mohamed, Albert Dobi, Taduru L. Sreenath, Shiv Srivastava, Roopa Biswas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Epigenetic regulation by SIRT1, a multifaceted NAD+-dependent protein deacetylase, is one of the most common factors modulating cellular processes in a broad range of diseases, including prostate cancer (CaP). SIRT1 is over-expressed in CaP cells, however the associated mechanism is not well understood. To identify whether specific microRNAs might mediate this linkage, we have screened a miRNA library for differential expression in ERG-associated CaP tissues. Of 20 differentially and significantly expressed miRNAs that distinguish ERG-positive tumors from ERG-negative tumors, we find miR-449a is highly suppressed in ERG-positive tumors. We establish that SIRT1 is a direct target of miR-449a and is also induced by ERG in ERG-associated CaP. Our data suggest that attenuation of miR-449a promotes the invasive phenotype of the ERG-positive CaP in part by inducing the expression of SIRT1 in prostate cancer cells. Furthermore, we also find that suppression of SIRT1 results in a significant reduction in ERG expression in ERG-positive CaP cells, indicating a feed-back regulatory loop associated with ERG, miR-449a and SIRT1. We also report that ERG suppresses p53 acetylation perhaps through miR-449a-SIRT1 axis in CaP cells. Our findings provide new insight into the function of miRNAs in regulating ERG-associated CaP. Thus, miR-449a activation or SIRT1 suppression may represent new therapeutic opportunity for ERG-associated CaP.

Original languageEnglish
Pages (from-to)22791-22806
Number of pages16
Issue number16
StatePublished - 19 Apr 2016
Externally publishedYes


  • ERG
  • MiR-449a
  • Prostate cancer
  • SIRT1
  • microRNA


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