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

Fredy Omar Beltrán-Anaya, Sandra Romero-Córdoba, Rosa Rebollar-Vega, Oscar Arrieta, Verónica Bautista-Piña, Carlos Dominguez-Reyes, Felipe Villegas-Carlos, Alberto Tenorio-Torres, Luis Alfaro-Riuz, Silvia Jiménez-Morales, Alberto Cedro-Tanda, Magdalena Ríos-Romero, Juan Pablo Reyes-Grajeda, Elda Tagliabue, Marilena V. Iorio, Alfredo Hidalgo-Miranda

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish
Pages (from-to)909-927
Number of pages19
JournalMolecular Oncology
Volume13
Issue number4
DOIs
Publication statusPublished - Apr 2019

Fingerprint

Long Noncoding RNA
Triple Negative Breast Neoplasms
Cell Movement
Cell Death
Breast Neoplasms
Cell Migration Inhibition
Neoplasms
Gene Expression Regulation
Apoptosis
Phenotype
Gene Expression
Genes

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 journalArticle

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 2019, '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', Molecular Oncology, vol. 13, no. 4, pp. 909-927. https://doi.org/10.1002/1878-0261.12446
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. / 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. In: Molecular Oncology. 2019 ; Vol. 13, No. 4. pp. 909-927.
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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.",
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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

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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.

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