Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 909-927 |
| Number of pages | 19 |
| Journal | Molecular Oncology |
| Volume | 13 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2019 |
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Keywords
- ENSG00000226738
- invasion
- LncKLHDC7B
- long non-coding RNA
- migration
- triple-negative breast cancer
ASJC Scopus subject areas
- Molecular Medicine
- Genetics
- Oncology
- Cancer Research
Cite this
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. / Beltrán-Anaya, Fredy Omar; Romero-Córdoba, Sandra; Rebollar-Vega, Rosa; Arrieta, Oscar; Bautista-Piña, Verónica; Dominguez-Reyes, Carlos; Villegas-Carlos, Felipe; Tenorio-Torres, Alberto; Alfaro-Riuz, Luis; Jiménez-Morales, Silvia; Cedro-Tanda, Alberto; Ríos-Romero, Magdalena; Reyes-Grajeda, Juan Pablo; Tagliabue, Elda; Iorio, Marilena V.; Hidalgo-Miranda, Alfredo.
In: Molecular Oncology, Vol. 13, No. 4, 04.2019, p. 909-927.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Beltrán-Anaya, Fredy Omar
AU - Romero-Córdoba, Sandra
AU - Rebollar-Vega, Rosa
AU - Arrieta, Oscar
AU - Bautista-Piña, Verónica
AU - Dominguez-Reyes, Carlos
AU - Villegas-Carlos, Felipe
AU - Tenorio-Torres, Alberto
AU - Alfaro-Riuz, Luis
AU - Jiménez-Morales, Silvia
AU - Cedro-Tanda, Alberto
AU - Ríos-Romero, Magdalena
AU - Reyes-Grajeda, Juan Pablo
AU - Tagliabue, Elda
AU - Iorio, Marilena V.
AU - Hidalgo-Miranda, Alfredo
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
KW - ENSG00000226738
KW - invasion
KW - LncKLHDC7B
KW - long non-coding RNA
KW - migration
KW - triple-negative breast cancer
UR - http://www.scopus.com/inward/record.url?scp=85063622683&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063622683&partnerID=8YFLogxK
U2 - 10.1002/1878-0261.12446
DO - 10.1002/1878-0261.12446
M3 - Article
C2 - 30648789
AN - SCOPUS:85063622683
VL - 13
SP - 909
EP - 927
JO - Molecular Oncology
JF - Molecular Oncology
SN - 1574-7891
IS - 4
ER -