Abstract A29: PIWI-like proteins and piRNAs in breast cancer cell proliferation and migration

Abstract

Breast cancer is the major cause of cancer-related death in women globally. With the revelation of key molecular pathways modulating all aspects of the breast cancer, the pharmaceutical development and clinical treatment have achieved significant progress. However, patients are still threatened by serious issues, including drug resistance, relapse and metastasis. In addition, a reliable and comprehensive system of early detection of the tumor is still lacking. As such, we set out to identify potential signaling pathway that could serve as novel drug target and diagnostic indicator. Recently, the PIWI (P-element-induced wimpy testis)-like proteins are gaining more interest as prospective biomarkers and targets for therapeutic development because of their re-expression in cancer cells. Initially, the PIWI-like proteins were regarded as germline-specific regulators. They have been revealed to exert important epigenetic functions in germ cells, including the suppression of retrotransposons, the formation of heterochromatin, and the maintenance of DNA methylation status. Surprisingly, in various human tumors, the abnormal expression of PIWI-like proteins was readily observed. The in vitro data showed that the repression of these proteins significantly slowed down the tumor growth, raising an intriguing question whether the PIWI-like proteins and the associated small RNAs, piRNAs, contribute to the breast cancer initiation and progression. In this study, we investigated the expression PIWI-like proteins and piRNAs in three different breast cell lines. It was found that in the normal mammalian epithelial cell line, MCF12A, there was a general lack of PIWI-like expression, which was unaffected by the addition of estrogen. In addition, there was no indication of piRNA generation and accumulation in MCF12A. However, in two breast cancer cell lines, MCF7 and MDA-MB-231, we detected robust expression of PIWI proteins and piRNAs. The knockdown of individual PIWI-like homologs significantly impacted two important indicators of the cancer, rapid proliferation and migration capacity. Furthermore, we found that the depletion of PIWI-like homologs repressed the expression of key regulators of pro-growth genes, such as CCND1, while enhancing those anti-proliferation factors and metastasis inhibitors, such as Bcl-2, p27, p53 and Oct-4. The data indicate that PIWI-like proteins could contribute to cancer formation and progression. We will further explore whether they exert these regulatory functions at the epigenetic level, just like in germ cells. Also, a comprehensive profiling of piRNAs in breast cancer will provide further clue about the clinical potential of using the PIWI/piRNA pathway as a screening indicator. Note: This abstract was not presented at the conference. Citation Format: Jing Yi Lee, Wai Cheong Yip, Qidong Hu. PIWI-like proteins and piRNAs in breast cancer cell proliferation and migration. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A29.