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

Abstract

Triple negative breast cancer ( TNBC ) represents an aggressive phenotype with poor prognosis compared with ER , PR, and HER 2‐positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non‐coding RNA (lnc RNA ) 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 lnc RNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of Lnc KLHDC 7B ( ENSG 00000226738 ). A total of 710 lnc RNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lnc RNA were independently validated. We discovered that Lnc KLHDC 7B ( ENSG 00000226738 ) acts as a transcriptional modulator of its neighboring coding gene KLHDC 7B in the immunomodulatory subtype. Furthermore, Lnc KLHDC 7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of Lnc KLHDC 7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of Lnc KLHDC 7B 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 KLHDC 7B and Lnc KLHDC 7B is associated with poor prognosis in patients with breast cancer.

LncRNA GATA3‐AS1 facilitates tumour progression and immune escape in triple‐negative breast cancer through destabilization of GATA3 but stabilization of PD‐L1

“…For example, Augoff K et al reported a lncRNA LOC554202 is regulated by promoter hypermethylation in TNBC 20 . LncKLHDC7B is enriched in TNBC and contributes to the migration and resistance to death of TNBC cells 21 . LncRNA MIR100HG with triplex formation with p27 loci and exerts oncogenic property in TNBC 22 .…”

Identification and potential mechanisms of a 4-lncRNA signature that predicts prognosis in patients with laryngeal cancer

“…For instance, Zhang K et al [22] observed that the lncRNA AOC4P promotes tumourigenesis and progression partly through epithelial-mesenchymal transition, thereby promoting a poor prognosis in gastric cancer. The study by Bo H et al [23] showed that the expression level of the lncRNA AFAP1-AS1 may be involved in the development of cervical cancer, and Beltrán-Anaya FO et al [24] confirmed that the low expression of LncKLHDC7B was associated with poor prognosis in patients with breast cancer.…”

Prognostic value of long non-coding RNAs in triple negative breast cancer

“…1 , a total of 31 articles published between 2015 and 2020 with 3146 TNBC patients were included in this meta-analysis. The 27 relevant lncRNAs were as follows: LINC00096, [ 11 ] SNHG12, [ 12 ] TCONS_l2_00002973, [ 13 ] MALAT1, [ 14 , 15 ] KDM5B, [ 16 ] ANRIL, [ 17 ] AFAP1-AS1, [ 18 ] ARNILA, [ 19 ] AWPPH, [ 20 ] DANCR, [ 21 , 22 ] GAS5, [ 23 , 24 ] ZEB2-AS1, [ 23 , 24 ] ADPGK-AS1, [ 26 ] POU3F3, [ 27 ] HIF1A-AS2, [ 28 ] MAPT-AS1, [ 29 ] NEF, [ 30 ] LUCAT1, [ 31 ] LINC00511, [ 32 ] HOTAIR, [ 33 , 34 ] MIR503HG, [ 35 ] LncKLHDC7B, [ 36 ] HULC, [ 37 ] linc-ZNF469–3, [ 38 ] NAMPT-AS, [ 39 ] LINC00173, [ 40 ] and HOST2. [ 41 ] Among the included studies, 29 studies were conducted in China, while the other 2 were performed in Mexico and Italy, respectively.…”