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

Overview

Journal Mol Oncol

Specialties Molecular Biology
Oncology

Date 2019 Jan 17

PMID 30648789

Citations 23

Authors

Fredy Omar Beltran-Anaya

Sandra Romero-Cordoba

Rosa Rebollar-Vega

Oscar Arrieta

Veronica Bautista-Pina

Carlos Dominguez-Reyes

Felipe Villegas-Carlos

Alberto Tenorio-Torres

Luis Alfaro-Riuz

Silvia Jimenez-Morales

Alberto Cedro-Tanda

Magdalena Rios-Romero

Juan Pablo Reyes-Grajeda

Elda Tagliabue

Marilena V Iorio

Alfredo Hidalgo-Miranda

Affiliations

Soon will be listed here.

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.

Citing Articles

The impact of ferroptosis and ferroptosis-related non-coding RNAs on breast cancer progression.

Liu W, Jiang C, Ma Y, Wang W, Peng J, Ma W Front Cell Dev Biol. 2025; 12:1506492.

PMID: 39763590 PMC: 11701165. DOI: 10.3389/fcell.2024.1506492.

LncRNA SOX9-AS1 triggers a transcriptional program involved in lipid metabolic reprogramming, cell migration and invasion in triple-negative breast cancer.

Cisneros-Villanueva M, Fonseca-Montano M, Rios-Romero M, Lopez-Camarillo C, Jimenez-Morales S, Langley E Sci Rep. 2024; 14(1):1483.

PMID: 38233470 PMC: 10794186. DOI: 10.1038/s41598-024-51947-2.

Roles of lncRNA in the diagnosis and prognosis of triple-negative breast cancer.

Yang Q, Fu Y, Wang J, Yang H, Zhang X J Zhejiang Univ Sci B. 2023; 24(12):1123-1140.

PMID: 38057269 PMC: 10710915. DOI: 10.1631/jzus.B2300067.

The current advances of lncRNAs in breast cancer immunobiology research.

Fonseca-Montano M, Vazquez-Santillan K, Hidalgo-Miranda A Front Immunol. 2023; 14:1194300.

PMID: 37342324 PMC: 10277570. DOI: 10.3389/fimmu.2023.1194300.

Metformin and long non-coding RNAs in breast cancer.

Gholami M, Klashami Z, Ebrahimi P, Mahboobipour A, Farid A, Vahidi A J Transl Med. 2023; 21(1):155.

PMID: 36849958 PMC: 9969691. DOI: 10.1186/s12967-023-03909-x.

References

Lim S, Yoo B, Kim H, Gilmore H, Lee Y, Lee H . Amyloid-β precursor protein promotes cell proliferation and motility of advanced breast cancer. BMC Cancer. 2014; 14:928. PMC: 4295427. DOI: 10.1186/1471-2407-14-928. View

Wapinski O, Chang H . Long noncoding RNAs and human disease. Trends Cell Biol. 2011; 21(6):354-61. DOI: 10.1016/j.tcb.2011.04.001. View

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

Heberle H, Meirelles G, da Silva F, Telles G, Minghim R . InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics. 2015; 16:169. PMC: 4455604. DOI: 10.1186/s12859-015-0611-3. View

Liu Y, Jiang Y, Xu X, Yu K, Jin X, Hu X . Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer. Breast Cancer Res. 2016; 18(1):33. PMC: 4791797. DOI: 10.1186/s13058-016-0690-8. View

Chen F, Kamradt M, Mulcahy M, Byun Y, Xu H, McKay M . Caspase proteolysis of the cohesin component RAD21 promotes apoptosis. J Biol Chem. 2002; 277(19):16775-81. DOI: 10.1074/jbc.M201322200. View

Gupta R, Shah N, Wang K, Kim J, Horlings H, Wong D . Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010; 464(7291):1071-6. PMC: 3049919. DOI: 10.1038/nature08975. View

Dent R, Trudeau M, Pritchard K, Hanna W, Kahn H, Sawka C . Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007; 13(15 Pt 1):4429-34. DOI: 10.1158/1078-0432.CCR-06-3045. View

Kim D, Rhee S . Matrix metalloproteinase‑2 regulates MDA‑MB‑231 breast cancer cell invasion induced by active mammalian diaphanous-related formin 1. Mol Med Rep. 2016; 14(1):277-82. DOI: 10.3892/mmr.2016.5282. View

10.

Langfelder P, Horvath S . WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008; 9:559. PMC: 2631488. DOI: 10.1186/1471-2105-9-559. View

11.

Zhao X, Liu X, Su L . Parthenolide induces apoptosis via TNFRSF10B and PMAIP1 pathways in human lung cancer cells. J Exp Clin Cancer Res. 2014; 33:3. PMC: 3892099. DOI: 10.1186/1756-9966-33-3. View

12.

Li J, Ma W, Zeng P, Wang J, Geng B, Yang J . LncTar: a tool for predicting the RNA targets of long noncoding RNAs. Brief Bioinform. 2014; 16(5):806-12. DOI: 10.1093/bib/bbu048. View

13.

Perez-Rodriguez G . [Prevalence of breast cancer sub-types by immunohistochemistry in patients in the Regional General Hospital 72, Instituto Mexicano del Seguro Social]. Cir Cir. 2015; 83(3):193-8. DOI: 10.1016/j.circir.2015.05.003. View

14.

Chen X, Li J, Gray W, Lehmann B, Bauer J, Shyr Y . TNBCtype: A Subtyping Tool for Triple-Negative Breast Cancer. Cancer Inform. 2012; 11:147-56. PMC: 3412597. DOI: 10.4137/CIN.S9983. View

15.

Kim J, Chen J, Lou Z . DBC1 is a negative regulator of SIRT1. Nature. 2008; 451(7178):583-6. DOI: 10.1038/nature06500. View

16.

Adams J, KELSO R, Cooley L . The kelch repeat superfamily of proteins: propellers of cell function. Trends Cell Biol. 1999; 10(1):17-24. DOI: 10.1016/s0962-8924(99)01673-6. View

17.

Diaz J, Mendoza P, Ortiz R, Diaz N, Leyton L, Stupack D . Rab5 is required in metastatic cancer cells for Caveolin-1-enhanced Rac1 activation, migration and invasion. J Cell Sci. 2014; 127(Pt 11):2401-6. PMC: 4074264. DOI: 10.1242/jcs.141689. View

18.

Li Y, Li L, Wang Z, Pan T, Sahni N, Jin X . LncMAP: Pan-cancer atlas of long noncoding RNA-mediated transcriptional network perturbations. Nucleic Acids Res. 2018; 46(3):1113-1123. PMC: 5815097. DOI: 10.1093/nar/gkx1311. View

19.

Bauer K, Brown M, Cress R, Parise C, Caggiano V . Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007; 109(9):1721-8. DOI: 10.1002/cncr.22618. View

20.

Tseng L, Bixby J . Interaction of an intracellular pentraxin with a BTB-Kelch protein is associated with ubiquitylation, aggregation and neuronal apoptosis. Mol Cell Neurosci. 2011; 47(4):254-64. PMC: 3137755. DOI: 10.1016/j.mcn.2011.04.005. View