THU492 Functional Characterization Of Nuclear-enriched Non-coding Genes In Triple-negative Breast Cancer

Abstract

Abstract Disclosure: V.A. Reid: None. R. Choudhari: None. B. Yang: None. E.I. Ramos: None. S. Dhandayuthapani: None. S. Gadad: None. Breast cancer, the top diagnosed cancer in women worldwide, is the second leading cause of cancer-related deaths in women. There are several molecular subtypes of breast cancer, which can be classified into two main groups, estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) subtypes. An ER+ diagnosis typically results in a better overall prognosis than ER- cases, as these tumors often have more available treatment options. Of the ER- subtypes, triple-negative breast cancer (TNBC) cases are the most aggressive and present the worst overall survival than any other molecular subtype. Recent studies have shown that long non-coding RNAs (lncRNAs) exhibit oncogenic or tumor-suppressive roles across different cancer types, in addition to traditionally being known to have multiple functions in regulating gene expression. Our previous studies demonstrated that lncRNA161 is regulated by estrogen, localized to chromatin, and regulates the estrogen-dependent growth of ER+ breast cancer cells and tumor growth. However, our current study revealed its opposite role in TNBC. We are investigating the role of lncRNA161 in TNBC cells utilizing multi-omics approaches, along with in vivo studies, to analyze multiple ER- cell lines, including the more aggressive TNBC subtype. Intriguingly, we found that doxycycline-induced expression of lncRNA161 in various TNBC cell lines attenuated the expression of several epithelial-to-mesenchymal transition (EMT) markers. In vivo, we observed that TNBC tumor growth was significantly decreased in mice after injection with MDA-MB-231 cells overexpressing lncRNA161. Together, our data indicate that lncRNA161 acts as a tumor suppressor in TNBCs, which could potentially lead to establishing it as a prognostic biomarker and therapeutic target for treating TNBCs in the future. S.S.G. is supported by grants from a) The Cancer Prevention and Research Institute of Texas (CPRIT; RR170020); b) Lizanell and Colbert Coldwell foundation; c) The Edward N. and Margaret G. Marsh Foundation; and d) The American Cancer Society Presentation: Thursday, June 15, 2023