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

BACKGROUND

Long non-coding RNAs (lncRNAs) have long been implicated in cancer-associated phenotypes. Recently, a class of lncRNAs, known as -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 has recently been described to be aberrantly expressed in lung adenocarcinoma (LUAD). However, the mechanisms mediating the expression of in LUAD remain unknown. Here we investigate the deregulation of a putative -acting lncRNA in LUAD, and its effect on the oncogene .

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 -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-, neighboring to be significantly downregulated in both LUAD cohorts. Conversely, we found significantly overexpressed in LUAD and anticorrelated with HMGA1-. experiments demonstrated siRNA-mediated inhibition of HMGA1- in immortalized non-malignant lung epithelial cells resulted in a significant increase in gene expression.

CONCLUSION

Our results suggest that HMGA1- is a novel -acting lncRNA that negatively regulates 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 .