RNA-Sequencing-Based lncRNA Biomarker Profiling on Triple Negative Breast Cancer

Authors

  • Lin Gao Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital); The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, Guangdong, P.R. China
  • Qinhe Yang Department of Integrated Chinese and Western Medicine, Jinan University, Guangzhou, Guangdong, P.R. China
  • Wenbin Zhou Department of Thyroid and Breast Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital); The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, Guangdong, P.R. China
  • Yong Dai Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital); The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, Guangdong, P.R. China
  • Jigang Wang Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital); The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, Guangdong, P.R. China
  • Li Fu Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pharmacology and International Cancer Center, Shenzhen University Health Science Center, Shenzhen 518060, Guangdong, China
  • Pan Zhao Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, the Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong, PR China
  • Jingy Huang Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital); The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, Guangdong, P.R. China
  • Malin Hong Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital); The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, Guangdong, P.R. China
  • Jinquan Xia Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital); The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, Guangdong, P.R. China
  • Chang Zou Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, the Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong, PR China

DOI:

https://doi.org/10.30683/1929-2279.2021.10.01

Keywords:

TNBC, long noncoding RNA (lncRNA), RNA-sequencing, ZEB1-AS1, TMEM254-AS1, LINC01087, LINC01122, LINC00856.

Abstract

Abstract: Basal-like triple-negative breast cancer (TNBC) is highly heterogeneous and lack of effective molecular targets for therapy. In this study, we developed the lncRNA signatures of TNBC as molecular biomarkers. RNA-sequencing in 12 paired breast cancer and adjacent tissues identified up-regulated and down-regulated lncRNAs of Basal subtype in contrast to Luminal A, Luminal B and HER2 subtypes. Additionally, Kaplan-Meier analysis revealed that high expression of lncRNA (ZEB1-AS1 and TMEM254-AS1) had a poor relapse-free survival rate (RFS), while high expression of lncRNA (LINC01087, LINC01122 and LINC00856) had a positive correlation with RFS. Furthermore, qRT-PCR analysis showed that the mRNA expressions of the ZEB1-AS1 and TMEM254-AS1 lncRNA were up-regulated in TNBC tissues, while the mRNA expression of lncRNA, including LINC01087, LINC01122 and LINC00856 were down-regulated in TNBC tissues. Taken together, our results elucidated that 5 novel lncRNAs, including ZEB1-AS1, TMEM254-AS1, LINC01087, LINC01122 and LINC00856 contributed to the progression of invasive TNBC. These lncRNAs could be molecular biomarkers for the development of TNBC treatment.

Keywords: TNBC, long noncoding RNA (lncRNA), RNA-sequencing, ZEB1-AS1, TMEM254-AS1, LINC01087, LINC01122, LINC00856.

References

Jiang YZ, Ma D, Suo C, Shi J, Xue M, Hu X, et al. Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies. Cancer Cell 2019; 35(3): 428-440 e425.

Jiang YZ, Liu YR, Xu XE, Jin X, Hu X, Yu KD, et al. Transcriptome Analysis of Triple-Negative Breast Cancer Reveals an Integrated mRNA-lncRNA Signature with Predictive and Prognostic Value. Cancer Res 2016; 76(8): 2105-2114.https://doi.org/10.1158/0008-5472.CAN-15-3284 DOI: https://doi.org/10.1158/0008-5472.CAN-15-3284

de la Mare JA, Contu L, Hunter MC, Moyo B, Sterrenberg JN, Dhanani KC, Mutsvunguma LZ, Edkins AL. Breast cancer: current developments in molecular approaches to diagnosis and treatment. Recent Pat Anticancer Drug Discov 2014; 9(2): 153-75.https://doi.org/10.2174/15748928113086660046 DOI: https://doi.org/10.2174/15748928113086660046

Huang JZ, Chen M, Chen, Gao XC, Zhu S, Huang H, et al. A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth. Mol Cell 2017; 68(1): 171-184 e176.https://doi.org/10.1016/j.molcel.2017.09.015 DOI: https://doi.org/10.1016/j.molcel.2017.09.015

Anastasiadou E, Jacob LS, Slack FJ. Non-coding RNA networks in cancer. Nat Rev Cancer 2018; 18(1): 5-18.https://doi.org/10.1038/nrc.2017.99 DOI: https://doi.org/10.1038/nrc.2017.99

Niknafs YS, Han S, Ma T, Speers C, Zhang C, Wilder-Romans K, et al. The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression. Nat Commun 2016; 7 12791.https://doi.org/10.1038/ncomms12791 DOI: https://doi.org/10.1038/ncomms12791

Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010; 464 (7291): 1071-1076.https://doi.org/10.1038/nature08975 DOI: https://doi.org/10.1038/nature08975

Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010; 26(1): 139-140.https://doi.org/10.1093/bioinformatics/btp616 DOI: https://doi.org/10.1093/bioinformatics/btp616

Soneson C, Delorenzi M. A comparison of methods for differential expression analysis of RNA-seq data. BMC Bioinformatics 2013; 14: 91.https://doi.org/10.1186/1471-2105-14-91 DOI: https://doi.org/10.1186/1471-2105-14-91

Liu K, Gao L, Ma X, Huang JJ, Chen J, Zeng L, et al. Long non-coding RNAs regulate drug resistance in cancer. Mol Cancer 2020; 19(1): 54.https://doi.org/10.1186/s12943-020-01162-0 DOI: https://doi.org/10.1186/s12943-020-01162-0

Moens S, Zhao P, Baietti MF, Marinelli O, Van Haver D, Impens F, et al. The mitotic checkpoint is a targetable vulnerability of carboplatin-resistant triple negative breast cancers. Sci Rep 2021; 11(1): 3176.https://doi.org/10.1038/s41598-021-82780-6 DOI: https://doi.org/10.1038/s41598-021-82780-6

Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z, et al. Upre-gulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma. Oncogene 2016; 35(12): 1575-1584.https://doi.org/10.1038/onc.2015.223 DOI: https://doi.org/10.1038/onc.2015.223

Su W, Xu M, Chen X, Chen N, Gong J, Nie L, et al. Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer. Mol Cancer 2017; 16(1): 142.https://doi.org/10.1186/s12943-017-0711-y DOI: https://doi.org/10.1186/s12943-017-0711-y

Lv QL, Hu L, Chen SH, Sun B, Fu ML, Qin CZ, et al. A Long Noncoding RNA ZEB1-AS1 Promotes Tumorigenesis and Predicts Poor Prognosis in Glioma. Int J Mol Sci 2016; 17(9).https://doi.org/10.3390/ijms17091431 DOI: https://doi.org/10.3390/ijms17091431

Shaath H, Vishnubalaji R, Elango R, Khattak S, Alajez N.M Single-cell long noncoding RNA (lncRNA) transcriptome implicates MALAT1 in triple-negative breast cancer (TNBC) resistance to neoadjuvant chemotherapy. Cell Death Discov 2021; 7(1): 23.https://doi.org/10.1038/s41420-020-00383-y DOI: https://doi.org/10.1038/s41420-020-00383-y

De Palma FDE, Del Monaco V, Pol JG, Kremer M, D'Argenio V, Stoll G, et al. The abundance of the long intergenic non-coding RNA 01087 differentiates between luminal and triple-negative breast cancers and predicts patient outcome. Pharmacol Res 2020; 161: 105249 DOI: https://doi.org/10.1016/j.phrs.2020.105249

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Published

2021-05-27 — Updated on 2021-05-27

How to Cite

Gao, L., Yang, Q., Zhou, W., Dai, Y., Wang, J., Fu, L., Zhao, P., Huang, J., Hong, M. ., Xia, J., & Zou, C. (2021). RNA-Sequencing-Based lncRNA Biomarker Profiling on Triple Negative Breast Cancer. Journal of Cancer Research Updates, 10, 1–9. https://doi.org/10.30683/1929-2279.2021.10.01

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Vol. 10 (2021)

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