Abstract 5589: Molecular diagnostic, prognostic and therapeutic role of mir-221 in pancreatic cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Comprehensive molecular profiling of microRNAs (miRNAs) and subsequent target gene analysis of pancreatic cancer (PaCa) can provide tumor specific miRNAs signatures to improve diagnostic accuracy, refine prognostic and predictive capabilities, and may also serve as therapeutic targets. In PaCa such a comprehensive analysis has not been reported.Design: RNA extracted from scant amounts of formalin fixed paraffin embedded PaCa tumor and normal pancreatic tissues were profiled for miRNA expression using microfluidic biochip microarrays (which interrogate 2019 unique mature miRNAs,LC Sciences). The expression of abnormal miRNAs was then validated and quantified using real time RT-PCR. Data was statistically analyzed using the Student's t-test. Survival data obtained in each case was correlated with the miRNA data using Kaplan-Meier analysis. Oncogenic potential, therapeutic modulation and downstream target genes of altered miRNA were evaluated by real time RT-PCR using PaCa cells for mRNA expression.Results: miRNA profiling showed high expression of miR-221 in PaCa tissues compared to normal pancreas (p=0.001). These findings were validated and quantified using qRT- PCR (p=0.0029) . Survival analysis using Kaplan-Meier, demonstrated shorter survival of patients with higher expression of miR-221 compared to those with relatively lower levels of miR-221 . The cell proliferation index of PaCa cells was increased by miR-221 mimics transfection and decreased by miR-221 inhibitors. The predicted target genes of miR-221 identified by RT-PCR were PTEN, p27kip1, p57kip2 and PUMA.Conclusions: High throughput miRNA expression profiling showed high expression of miR-221 in PaCa tissues. Higher levels of miR-221 demonstrated poorer prognosis, suggesting the oncogenic potential of miR-221 in PaCa. Its target genes are PTEN, p27kip1, p57kip2 and PUMA which are tumor suppressors, and found to be deregulated by over-expression or under-expression of miR-221 transfection studies in PaCa cells. These results provide molecular evidence of oncogenic potential of miR-221 in PaCa which may have a significant clinical impact on prognosis & risk stratification and in designing novel targeted molecular therapeutics in the future to achieve the goal of personalized and precision medicine. Citation Format: Seema Sethi, Shaan Sarkar, Hala Dubaybo, Shadan Ali, Priscila Goncalves, Spilakshmi Kollepara, Philip Philip, Yiwei Li. Molecular diagnostic, prognostic and therapeutic role of mir-221 in pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5589. doi:10.1158/1538-7445.AM2014-5589