Poster abstracts
Poster number 30 submitted by Zhengmin Cong
MANCR modulates breast cancer metastasis by influencing Net1a expression in cis
Zhengmin Cong (Cell and Developmental Biology, UIUC), Deepak K. Singh (Department of Cell Biology, Albert Einstein College of Medicine), Sarath C. Janga (School of Informatics and Computing, Indiana University & Purdue University), You-Jin Song, Minxue Liu, Dazhen Liu (Cell and Developmental Biology, UIUC), Ashish Lal (National Institutes of Health), Kannanganattu V. Prasanth (Cell and Developmental Biology, UIUC)
Abstract:
Breast cancer is the most common cancer type among women, whose rapid proliferation and metastasis usually result in poor prognosis. LncRNAs play a crucial role in gene regulation, and their aberrant expression is often observed in various diseases, including breast cancer. To gain more insights into the role of lncRNAs in breast cancer progression, we determine differential lncRNA expression in isogenic breast cancer cell lines (M1-M4) and triple-negative breast cancer (TNBC) patients. These analyses identified several hundreds of lncRNAs, including the nuclear-enriched Mitotically-Associated lncRNA (MANCR) that are aberrantly expressed in metastatic breast cancer cells compared to non-tumorigenic mammary epithelial cells. The observed concordance of elevated MANCR expression between metastatic M4 cell line and TNBC patients underscores the relevance and potential clinical significance of the MANCR gene. MANCR is induced by various stresses, such as DNA damage and hypoxia, and its expression is negatively related to proliferation. Surprisingly, MANCR inhibits metastasis since its knockdown significantly suppresses cell migration and invasion in vitro and lung colonization in vivo. Mechanistically, MANCR promotes the expression of Net1A, which is Rho-GEF known to regulate DNA damage response, cell proliferation, and metastasis. MANCR influences the molecular interaction between Net1A and hnRNPL, thereby contributing to Ne1A differential expression in BC cells. Knockdown of either hnRNPL or Net1a generates a similar phenotype to MANCR knockdown. Our results show that MANCR can modulate breast cancer proliferation and metastasis by regulating Net1A expression and potentially by influencing hnRNPL-Net1A interaction.
Keywords: lncRNA, breast cancer, metastasis