Expression of Long non-coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death.

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Expression of Long non-coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death.

Mol Oncol. 2019 Jan 16;:

Authors: Beltrán-Anaya FO, Romero-Córdoba S, Rebollar-Vega R, Arrieta O, Bautista-Piña V, Dominguez-Reyes C, Villegas-Carlos F, Tenorio-Torres A, Alfaro-Riuz L, Jiménez-Morales S, Cedro-Tanda A, Ríos-Romero M, Reyes-Grajeda JP, Tagliabue E, Iorio MV, Hidalgo-Miranda A

Abstract
Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared to ER, PR and HER2 positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNAs in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNAs were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNAs were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Taken together, our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.

PMID: 30648789 [PubMed - as supplied by publisher]

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