@article{2113d5c6cb4144018f8cd7774e2e2cfc,
title = "LncRNA-mediated regulation of SOX9 expression in basal subtype breast cancer cells",
abstract = "Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer (BC) subtypes with a poor prognosis and high recurrence rate. Recent studies have identified vital roles played by several lncRNAs (long noncoding RNAs) in BC pathobiology. Cell type-specific expression of lncRNAs and their potential role in regulating the expression of oncogenic and tumor suppressor genes have made them promising cancer drug targets. By performing a transcriptome screen in an isogenic TNBC/basal subtype BC progression cell line model, we recently reported ∼1800 lncRNAs that display aberrant expression during breast cancer progression. Mechanistic studies on one such nuclear-retained lncRNA, linc02095, reveal that it promotes breast cancer proliferation by facilitating the expression of oncogenic transcription factor, SOX9. Both linc02095 and SOX9 display coregulated expression in BC patients as well in basal subtype BC cell lines. Knockdown of linc02095 results in decreased BC cell proliferation, whereas its overexpression promotes cells proliferation. Linc02095-depleted cells display reduced expression of SOX9 concomitant with reduced RNA polymerase II occupancy at the SOX9 gene body as well as defective SOX9 mRNA export, implying that linc02095 positively regulates SOX9 transcription and mRNA export. Finally, we identify a positive feedback loop in BC cells that controls the expression of both linc02095 and SOX9. Thus, our results unearth tumor-promoting activities of a nuclear lncRNA linc02095 by facilitating the expression of key oncogenic transcription factor in BC.",
keywords = "Basal-like subtype, Enhancer, Nuclear lncRNA, Regulation, TNBC",
author = "Aamira Tariq and Qinyu Hao and Qinyu Sun and Singh, {Deepak K.} and Mahdieh Jadaliha and Yang Zhang and Neha Chetlangia and Jian Ma and Holton, {Sarah E.} and Rohit Bhargava and Ashish Lal and Prasanth, {Supriya G.} and Prasanth, {Kannanganattu V.}",
note = "Funding Information: We thank members of Dr. Prasanth{\textquoteright}s laboratory for their valuable comments. We thank Dr. Xinying Zong for technical assistance. This work was supported by the National Institutes of Health (National Institute of General Medical Sciences grants GM088252 to K.V.P., GM099669 and GM125196 to S.G.P.); Cancer Center at Illinois seed grant and Prairie Dragon Paddlers to K.V.P., National Science Foundation (EAGER grant to K.V.P. [1723008] and career award [1243372] and 1818286 to S.G.P.). A.L. was supported by the Intramural Research Program of the Funding Information: National Cancer Institute (NCI), Center for Cancer Research (CCR). A.T. was supported by a Fulbright fellowship. M.J. was supported by a UIUC dissertation completion fellowship. R.B. was supported by R01EB009745. Funding Information: We thank members of Dr. Prasanth{\textquoteright}s laboratory for their valuable comments. We thank Dr. Xinying Zong for technical assistance. This work was supported by the National Institutes of Health (National Institute of General Medical Sciences grants GM088252 to K.V.P., GM099669 and GM125196 to S.G.P.); Cancer Center at Illinois seed grant and Prairie Dragon Paddlers to K.V.P., National Science Foundation (EAGER grant to K.V.P. [1723008] and career award [1243372] and 1818286 to S.G.P.). A.L. was supported by the Intramural Research Program of the National Cancer Institute (NCI), Center for Cancer Research (CCR). A.T. was supported by a Fulbright fellowship. M.J. was supported by a UIUC dissertation completion fellowship. R.B. was supported by R01EB009745. Publisher Copyright: {\textcopyright} 2020 Tariq et al.",
year = "2020",
doi = "10.1261/rna.073254.119",
language = "English (US)",
volume = "26",
pages = "175--185",
journal = "RNA",
issn = "1355-8382",
publisher = "Cold Spring Harbor Laboratory Press",
number = "2",
}
