Deregulation of a Cis -Acting lncRNA in Non-small Cell Lung Cancer May Control HMGA1 Expression.

Autor:	Stewart GL; Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, BC, Canada., Sage AP; Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, BC, Canada., Enfield KSS; Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, BC, Canada., Marshall EA; Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, BC, Canada., Cohn DE; Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, BC, Canada., Lam WL; Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, BC, Canada.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2021 Jan 11; Vol. 11, pp. 615378. Date of Electronic Publication: 2021 Jan 11 (Print Publication: 2020).
DOI:	10.3389/fgene.2020.615378
Abstrakt:	Background: Long non-coding RNAs (lncRNAs) have long been implicated in cancer-associated phenotypes. Recently, a class of lncRNAs, known as cis -acting, have been shown to regulate the expression of neighboring protein-coding genes and may represent undiscovered therapeutic action points. The chromatin architecture modification gene HMGA1 has recently been described to be aberrantly expressed in lung adenocarcinoma (LUAD). However, the mechanisms mediating the expression of HMGA1 in LUAD remain unknown. Here we investigate the deregulation of a putative cis -acting lncRNA in LUAD, and its effect on the oncogene HMGA1 . Methods: LncRNA expression was determined from RNA-sequencing data of tumor and matched non-malignant tissues from 36 LUAD patients. Transcripts with significantly deregulated expression were identified and validated in a secondary LUAD RNA-seq dataset (TCGA). SiRNA-mediated knockdown of a candidate cis -acting lncRNA was performed in BEAS-2B cells. Quantitative real-time PCR was used to observe the effects of lncRNA knockdown on the expression of HMGA1. Results: We identified the lncRNA RP11.513I15.6, which we refer to as HMGA1- lnc , neighboring HMGA1 to be significantly downregulated in both LUAD cohorts. Conversely, we found HMGA1 significantly overexpressed in LUAD and anticorrelated with HMGA1- lnc . In vitro experiments demonstrated siRNA-mediated inhibition of HMGA1- lnc in immortalized non-malignant lung epithelial cells resulted in a significant increase in HMGA1 gene expression. Conclusion: Our results suggest that HMGA1- lnc is a novel cis -acting lncRNA that negatively regulates HMGA1 gene expression in lung cells. Further characterization of this regulatory mechanism may advance our understanding of the maintenance of lung cancer phenotypes and uncover a novel therapeutic intervention point for tumors driven by HMGA1 . Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Stewart, Sage, Enfield, Marshall, Cohn and Lam.)
Databáze:	MEDLINE
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