BCL11A Confers Cell Invasion and Migration in Androgen Receptor-positive Triple-negative Breast Cancer

Overview

Journal Oncol Lett

Specialty Oncology

Date 2020 Mar 29

PMID 32218847

Citations 8

Authors

Xin Wang

Yumei Xu

Kun Xu

Yajuan Chen

Xiudi Xiao

Xiaoxiang Guan

Affiliations

Soon will be listed here.

Abstract

Triple-negative breast cancer (TNBC) is associated with poor clinical prognosis due to a lack of effective therapeutic options. The expression of B-cell lymphoma/leukemia 11A (BCL11A) has been indicated to correlate with TNBC carcinogenesis, though the precise mechanisms of BCL11A-induced tumorigenesis in TNBC remain unclear. Using data retrieved from The Cancer Genome Atlas (TCGA) database, the present study demonstrated that BCL11A expression was upregulated in TNBC, compared with other types of breast cancer. Furthermore, in a tissue microarray of 140 patients with breast cancer, an elevated BCL11A level was correlated with unfavorable overall survival (OS), and exogenous BCL11A-knockdown was subsequently verified to inhibit tumor growth and metastasis in TNBC. Notably, the same tissue microarray revealed that a favorable patient outcome was associated with high expression levels of BCL11A and androgen receptor (AR). Moreover, BCL11A-knockdown significantly inhibited the expression level of AR and further had an influence on proliferation, migration and invasion in TNBC cell lines. Collectively, the results of the current study indicate the function of BCL11A in TNBC progression, and provide new insights into the unique mechanism of BCL11A in AR regulation, emphasizing the significance of more research on BCL11A and AR regulation in TNBC molecular treatment.

Citing Articles

A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis.

Hu Y, He Y, Luo N, Li X, Guo L, Zhang K Cancer Biol Ther. 2023; 24(1):2235768.

PMID: 37548553 PMC: 10408694. DOI: 10.1080/15384047.2023.2235768.

RNA-seq analysis reveals candidate genes associated with proliferation, invasion, and migration in BCL11A knockdown B-NHL cell lines.

Yin J, Xie X, Quan Y, Wang Z, Liu S, Su Q Ann Hematol. 2023; 102(7):1845-1856.

PMID: 37148312 DOI: 10.1007/s00277-023-05247-w.

Invention of 3Mint for feature grouping and scoring in multi-omics.

Unlu Yazici M, Marron J, Bakir-Gungor B, Zou F, Yousef M Front Genet. 2023; 14:1093326.

PMID: 37007972 PMC: 10050723. DOI: 10.3389/fgene.2023.1093326.

Triple-negative Breast Cancer: Identification of circRNAs With Efficacy in Preclinical Models.

Weidle U, Birzele F Cancer Genomics Proteomics. 2023; 20(2):117-131.

PMID: 36870692 PMC: 9989670. DOI: 10.21873/cgp.20368.

The DNA repair function of BCL11A suppresses senescence and promotes continued proliferation of triple-negative breast cancer cells.

Vickridge E, Faraco C, Tehrani P, Ramdzan Z, Rahimian H, Leduy L NAR Cancer. 2022; 4(4):zcac028.

PMID: 36186110 PMC: 9516615. DOI: 10.1093/narcan/zcac028.

References

Skor M, Wonder E, Kocherginsky M, Goyal A, Hall B, Cai Y . Glucocorticoid receptor antagonism as a novel therapy for triple-negative breast cancer. Clin Cancer Res. 2013; 19(22):6163-72. PMC: 3860283. DOI: 10.1158/1078-0432.CCR-12-3826. View

He J, Peng R, Yuan Z, Wang S, Peng J, Lin G . Prognostic value of androgen receptor expression in operable triple-negative breast cancer: a retrospective analysis based on a tissue microarray. Med Oncol. 2011; 29(2):406-10. DOI: 10.1007/s12032-011-9832-0. View

Saiki Y, Yamazaki Y, Yoshida M, Katoh O, Nakamura T . Human EVI9, a homologue of the mouse myeloid leukemia gene, is expressed in the hematopoietic progenitors and down-regulated during myeloid differentiation of HL60 cells. Genomics. 2001; 70(3):387-91. DOI: 10.1006/geno.2000.6385. View

Millikan R, Newman B, Tse C, Moorman P, Conway K, Dressler L . Epidemiology of basal-like breast cancer. Breast Cancer Res Treat. 2007; 109(1):123-39. PMC: 2443103. DOI: 10.1007/s10549-007-9632-6. View

Vera-Badillo F, Templeton A, de Gouveia P, Diaz-Padilla I, Bedard P, Al-Mubarak M . Androgen receptor expression and outcomes in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2013; 106(1):djt319. DOI: 10.1093/jnci/djt319. View

Yang F, Shen Y, Zhang W, Jin J, Huang D, Fang H . An androgen receptor negatively induced long non-coding RNA ARNILA binding to miR-204 promotes the invasion and metastasis of triple-negative breast cancer. Cell Death Differ. 2018; 25(12):2209-2220. PMC: 6261952. DOI: 10.1038/s41418-018-0123-6. View

Satterwhite E, Sonoki T, Willis T, Harder L, Nowak R, Arriola E . The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. Blood. 2001; 98(12):3413-20. DOI: 10.1182/blood.v98.12.3413. View

Lazarus K, Hadi F, Zambon E, Bach K, Santolla M, Watson J . BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma. Nat Commun. 2018; 9(1):3327. PMC: 6102279. DOI: 10.1038/s41467-018-05790-5. View

Agueli C, Cammarata G, Salemi D, Dagnino L, Nicoletti R, La Rosa M . 14q32/miRNA clusters loss of heterozygosity in acute lymphoblastic leukemia is associated with up-regulation of BCL11a. Am J Hematol. 2010; 85(8):575-8. DOI: 10.1002/ajh.21758. View

10.

He D, Wu H, Ding L, Li Y . Combination of BCL11A siRNA with vincristine increases the apoptosis of SUDHL6 cells. Eur J Med Res. 2014; 19:34. PMC: 4086990. DOI: 10.1186/2047-783X-19-34. View

11.

Kaneda H, Arao T, Tanaka K, Tamura D, Aomatsu K, Kudo K . FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth. Cancer Res. 2010; 70(5):2053-63. DOI: 10.1158/0008-5472.CAN-09-2161. View

12.

Zhang W, Luo J, Yang F, Wang Y, Yin Y, Strom A . BRCA1 inhibits AR-mediated proliferation of breast cancer cells through the activation of SIRT1. Sci Rep. 2016; 6:22034. PMC: 4763204. DOI: 10.1038/srep22034. View

13.

Boelens M, Kok K, Van der Vlies P, van der Vries G, Sietsma H, Timens W . Genomic aberrations in squamous cell lung carcinoma related to lymph node or distant metastasis. Lung Cancer. 2009; 66(3):372-8. DOI: 10.1016/j.lungcan.2009.02.017. View

14.

Tsang J, Yu Y, Burke S, Buettner F, Wang C, Kolodziejczyk A . Single-cell transcriptomic reconstruction reveals cell cycle and multi-lineage differentiation defects in Bcl11a-deficient hematopoietic stem cells. Genome Biol. 2015; 16:178. PMC: 4576406. DOI: 10.1186/s13059-015-0739-5. View

15.

Lehmann B, Bauer J, Chen X, Sanders M, Chakravarthy A, Shyr Y . Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011; 121(7):2750-67. PMC: 3127435. DOI: 10.1172/JCI45014. View

16.

Mrklic I, Pogorelic Z, capkun V, Tomic S . Expression of androgen receptors in triple negative breast carcinomas. Acta Histochem. 2012; 115(4):344-8. DOI: 10.1016/j.acthis.2012.09.006. View

17.

Chetaille B, Bertucci F, Finetti P, Esterni B, Stamatoullas A, Picquenot J . Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome. Blood. 2008; 113(12):2765-3775. DOI: 10.1182/blood-2008-07-168096. View

18.

Jiang B, Zhang X, Su J, Meng W, Yang X, Yang J . BCL11A overexpression predicts survival and relapse in non-small cell lung cancer and is modulated by microRNA-30a and gene amplification. Mol Cancer. 2013; 12:61. PMC: 3695801. DOI: 10.1186/1476-4598-12-61. View

19.

Podgornik H, Pretnar J, Skopec B, Andoljsek D, cernelc P . Concurrent rearrangements of BCL2, BCL3, and BCL11A genes in atypical chronic lymphocytic leukemia. Hematology. 2013; 19(1):45-8. DOI: 10.1179/1607845413Y.0000000078. View

20.

Kapatai G, Murray P . Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin lymphoma. J Clin Pathol. 2007; 60(12):1342-9. PMC: 2095570. DOI: 10.1136/jcp.2007.050146. View