THU489 The Role Of Noncoding Genes With The Bidirectional Promoter In Triple-negative Breast Cancer

Abstract

Abstract Disclosure: B. Yang: None. M. Sedano: None. M.V. Jimenez: None. E.I. Ramos: None. S. Gadad: None. Breast cancer is the second leading cause of cancer mortality in women after lung cancer. Breast cancer is grouped into different molecular subtypes; triple-negative breast cancer (TNBC) accounts for 20%. TNBC is a highly aggressive histologic subtype; the lack of unique therapeutic targets makes it harder to treat. Recent studies have implicated genes involved in cancers that are transcribed using a process known as divergent transcription. The expression of these genes is tightly regulated; however, many escape regulation and become aberrantly expressed in tumors. Interestingly, our genomic analysis suggests that several of these genes encode noncoding transcripts. Analysis of transcriptome from different tissue types, including cancer and normal, revealed that many are upregulated in various cancers. Selected divergent transcript, such as lncRNA67, has been completely characterized (transcription start and stop site, 5’ cap, polyA tail, and exon/intron structure) and cloned. In functional assays, overexpression of lncRNA67 regulates gene expression, cell proliferation, and tumor growth. Our molecular analyses indicate that lncRNA67 plays a vital role in triple-negative breast cancer biology. Collectively, our results suggest that divergent transcripts are an integral component of cancer biology and present a new repertoire of diagnostic and potential therapeutic targets. Presentation: Thursday, June 15, 2023