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
; 13(4): 909-927, 2019 04.
Article
in En
| MEDLINE
| ID: mdl-30648789
Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with 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 RNA (lncRNA) 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 lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA 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. 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation, Neoplastic
/
Cell Movement
/
Apoptosis
/
Immunomodulation
/
RNA, Long Noncoding
/
Triple Negative Breast Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
/
Middle aged
Language:
En
Journal:
Mol Oncol
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2019
Document type:
Article
Affiliation country:
Mexico
Country of publication:
United States