MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular senescence.

Malathi Ramalinga,Deepak Kumar,Anvesha Srivastava,Simeng Suy,Arpita Roy,Sean Collins,Varsha Harish,Asmita Bhattarai

doi:10.18632/oncotarget.5920

Malathi Ramalinga, Deepak Kumar + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.5920

Copy DOI

Abstract

Among a number of non-coding RNAs, role of microRNAs (miRNAs) in cancer cell proliferation, cancer initiation, development and metastasis have been extensively studied and miRNA based therapeutic approaches are being pursued. Prostate cancer (PCa) is a major health concern and several deregulated miRNAs have been described in PCa. miR-212 is differentially modulated in multiple cancers however its function remains elusive. In this study, we found that miR-212 is downregulated in PCa tissues when compared with benign adjacent regions (n = 40). Also, we observed reduced levels of circulatory miR-212 in serum from PCa patients (n = 40) when compared with healthy controls (n = 32). Elucidating the functional role of miR-212, we demonstrate that miR-212 negatively modulates starvation induced autophagy in PCa cells by targeting sirtuin 1 (SIRT1). Overexpression of miR-212 also leads to inhibition of angiogenesis and cellular senescence. In conclusion, our study indicates a functional role of miR-212 in PCa and suggests the development of miR-212 based therapies.

Highlights

Prostate cancer (PCa) claimed ~29,480 deaths in US in 2014 and estimates 220,800 new cases in 2015 [1, 2]
To test if miR-212 expression lowers the levels of expression of sirtuin 1 (SIRT1), PCa cells were transfected with miR-212 or scrambled negative control (NC) mimics
We have demonstrated that miR-212 which is known to be downregulated in PCa, modulates autophagy, angiogenesis and senescence

Summary

INTRODUCTION

Prostate cancer (PCa) claimed ~29,480 deaths in US in 2014 and estimates 220,800 new cases in 2015 [1, 2]. MiRNA deregulation has been linked to cancer initiation and progression where miRNAs act as tumor suppressors or oncogenes, regulating multiple pathways including cell proliferation, differentiation, apoptosis, metastasis, autophagy, angiogenesis and senescence [14, 19, 20]. Because of their small size and secondary structure, mature miRNAs are highly stable for their utility as biomarkers of prediction, diagnosis/ prognosis and disease progression (including survival and recurrence). Together the study supports the role of miR-212 in the development of PCa

RESULTS

DISCUSSION

MATERIALS AND METHODS