Abstract 3067: Expression of miR-301a regulates metastasis and act as a lethal marker for prostate cancer

Prostate Specific Antigen (PSA) screening contributes as a biomarker for diagnosis of prostate cancer; however, PSA screening has been considered an over diagnosis in some cases. This has lead to the identification of novel invasive markers which could eventually differentiate patients with lethal prostate cancer from those with indolent disease. Emerging evidences suggest that a small set of microRNAs (miRNA) are linked to prostate cancer pathogenesis leading to castration resistant prostate cancer (CRPC). In our studies of genome wide miRNA profiling, we have found that miR-301a is highly expressed in prostate cancer (CaP) cell lines as compared to normal prostate epithelial cells. While analyzing CaP samples, we found higher expression of miR-301a at specific stages. Interestingly, the miR-301a induction varies from 10 to 250 fold in aggressive tumors which clearly correlate with metastases. To confirm these findings, we utilized metastatic lesions from transgenic mice model of Trans Adenocarcinoma of Mouse Prostate (TRAMP) tissues, where higher levels of miR301a expression were observed in prostate tumors in comparison with normal prostate. Further, micro dissecting the tumors (metastasis) from lung showed ∼15 fold induction of miR301a expression compared to the normal lung components. Silencing specifically miR-301a resulted in the inhibition of proliferation, colony forming abilities, invasion, and migration and cell adhesion properties in CaP cell lines. Our molecular studies also suggest that miR-301 regulates Rho GTPases family proteins and transcriptionally activates Epithelial-Mesenchymal-Transition (EMT) markers like slug and β-catenin. Our ongoing studies may not only reveal whether miR-301 regulates Rho-associated kinases (ROCK) but also the potential role of EMT in CaP. Furthermore, we intend to perform a case control study by screening an additional 100 CaP cases besides indolent controls. As mentioned earlier, besides revealing the functional role in CaP pathogenesis, results from these findings will also suggest whether miR-301 expression distinguishes lethal CaP from indolent disease. Citation Format: Trinath P. Das, Suman Suman, Arokya Ms PapuJohn, Akhila Ankhem, Sandhya R. Rao, Jamie C. Messer, Houda Alatassi, Murali M. Ankhem, Chendil Damodaran. Expression of miR-301a regulates metastasis and act as a lethal marker for prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3067. doi:10.1158/1538-7445.AM2015-3067