Abstract
Abstract Prostate cancer (PCa), a leading cause of male cancer related mortality, is dependent upon androgens acting via androgen receptor (AR) signaling. Androgen targeted therapies are often used as the first line of treatment for prostate cancer that are effective initially. However, PCa eventually progresses to castration-resistant stage that has limited treatment options. Castration-resistant prostate cancer (CRPC) is treated by second generation of AR pathway inhibitors such as Enzalutamide and Abiraterone. Resistance to these agents develop owing to various mechanisms such as evolution to androgen-independent neuroendocrine prostate cancer (NEPC). In this study, we examined the potential role of miR-410 in different stages of prostate cancer. Analyses of miR-410 in PCa clinical samples and patient-derived xenograft (PDX) models showed that miR-410 is frequently upregulated in PCa. Its expression was further increased in CRPC cases with neuroendocrine differentiation (NED). We examined the functional role of miR-410 by stably expressing miR-410 in androgen dependent and androgen independent cell lines. Our data suggests a context dependent role of miR-410 in prostate cancer cell lines. In androgen independent cell line, miR-410 plays an oncogenic role by impacting epithelial to mesenchymal transition (EMT) via directly targeting SNAIL. Also, it was found to increase the expression of neuronal genes such as Synaptophysin and neural transcription factor BRN2. However, in androgen dependent cell line, miR-410 was found to target PTEN. In conclusion, our data suggests that miR-410 play an important regulatory role in prostate cancer with effects on EMT and neuronal differentiation programs. Citation Format: Amritha Sreekumar, Nikhil Patel, Sharanjot Saini. Regulatory role of miR-410 in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1543.
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