Full Text:   <288>

Summary:  <77>

CLC number: 

On-line Access: 2023-12-08

Received: 2023-01-29

Revision Accepted: 2023-06-24

Crosschecked: 2023-12-12

Cited: 0

Clicked: 481

Citations:  Bibtex RefMan EndNote GB/T7714


Xi-Ping Zhang


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.12 P.1123-1140


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

Author(s):  Qiuhui YANG, Yeqin FU, Jiaxuan WANG, Hongjian YANG, Xiping ZHANG

Affiliation(s):  Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; more

Corresponding email(s):   zxp99688@sina.com

Key Words:  Triple-negative breast cancer (TNBC), Long non-coding RNA (lncRNA), Diagnosis, Prognosis, Chemotherapy resistance

Qiuhui YANG, Yeqin FU, Jiaxuan WANG, Hongjian YANG, Xiping ZHANG. Roles of lncRNA in the diagnosis and prognosis of triple-negative breast cancer[J]. Journal of Zhejiang University Science B, 2023, 24(12): 1123-1140.

@article{title="Roles of lncRNA in the diagnosis and prognosis of triple-negative breast cancer",
author="Qiuhui YANG, Yeqin FU, Jiaxuan WANG, Hongjian YANG, Xiping ZHANG",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Roles of lncRNA in the diagnosis and prognosis of triple-negative breast cancer
%A Qiuhui YANG
%A Yeqin FU
%A Jiaxuan WANG
%A Hongjian YANG
%A Xiping ZHANG
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 12
%P 1123-1140
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300067

T1 - Roles of lncRNA in the diagnosis and prognosis of triple-negative breast cancer
A1 - Qiuhui YANG
A1 - Yeqin FU
A1 - Jiaxuan WANG
A1 - Hongjian YANG
A1 - Xiping ZHANG
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 12
SP - 1123
EP - 1140
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300067

Breast cancer is a malignant tumor that seriously endangers women’s lives. The prognosis of breast cancer patients differs among molecular types. Compared with other subtypes, triple-negative breast cancer (TNBC) has been a research hotspot in recent years because of its high degree of malignancy, strong invasiveness, rapid progression, easy of recurrence, distant metastasis, poor prognosis, and high mortality. Many studies have found that long non-coding RNA (lncRNA) plays an important role in the occurrence, proliferation, migration, recurrence, chemotherapy resistance, and other characteristics of TNBC. Some lncRNAs are expected to become biomarkers in the diagnosis and prognosis of TNBC, and even new targets for its treatment. Based on a PubMed literature search, this review summarizes the progress in research on lncRNAs in TNBC and discusses their roles in TNBC diagnosis, prognosis, and chemotherapy with the hope of providing help for future research.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]AbramsonVG, LehmannBD, BallingerTJ, et al., 2015. Subtyping of triple-negative breast cancer: implications for therapy. Cancer, 121(1):8-16.

[2]Beltrán-AnayaFO, Romero-CórdobaS, Rebollar-VegaR, et al., 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. Mol Oncol, 13(4):909-927.

[3]BorriF, GranagliaA, 2021. Pathology of triple negative breast cancer. Semin Cancer Biol, 72:136-145.

[4]CaoW, ChenHD, YuYW, et al., 2021. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J, 134(7):783-791.

[5]CareyL, WinerE, VialeG, et al., 2010. Triple-negative breast cancer: disease entity or title of convenience? Nat Rev Clin Oncol, 7(12):683-692.

[6]ChenWQ, ZhengRS, ZhangSW, et al., 2017. Cancer incidence and mortality in China, 2013. Cancer Lett, 401:‍63-71.

[7]DjebaliS, DavisCA, MerkelA, et al., 2012. Landscape of transcription in human cells. Nature, 489(7414):101-108.

[8]FanHJ, YuanJ, LiXY, et al., 2020. LncRNA LINC00173 enhances triple-negative breast cancer progression by suppressing miR-490-3p expression. Biomed Pharmacother, 125:109987.

[9]FengLL, ShenFR, ZhouJH, et al., 2019. Expression of the lncRNA ZFAS1 in cervical cancer and its correlation with prognosis and chemosensitivity. Gene, 696:105-112.

[10]FoulkesWD, SmithIE, Reis-FilhoJS, 2010. Triple-negative breast cancer. N Engl J Med, 363(20):1938-1948.

[11]FuJ, DongGJ, ShiH, et al., 2019. LncRNA MIR503HG inhibits cell migration and invasion via miR-103/OLFM4 axis in triple negative breast cancer. J Cell Mol Med, 23(7):4738-4745.

[12]FuPF, ZhengX, FanX, et al., 2019. Role of cytoplasmic lncRNAs in regulating cancer signaling pathways. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(1):1-8.

[13]Ghafouri-FardS, FathiM, ZhaiTY, et al., 2021. LncRNAs: novel biomarkers for pancreatic cancer. Biomolecules, 11(11):1665.

[14]GizaDE, VasilescuC, CalinGA, 2014. MicroRNAs and ceRNAs: therapeutic implications of RNA networks. Expert Opin Biol Ther, 14(9):1285-1293.

[15]HanJG, HanBJ, WuXY, et al., 2018. Knockdown of lncRNA H19 restores chemo-sensitivity in paclitaxel-resistant triple-negative breast cancer through triggering apoptosis and regulating Akt signaling pathway. Toxicol Appl Pharmacol, 359:55-61.

[16]HatemR, el BottyR, Chateau-JoubertS, et al., 2016. Targeting mTOR pathway inhibits tumor growth in different molecular subtypes of triple-negative breast cancers. Oncotarget, 7(30):48206-48219.

[17]HeYY, XiaoB, LeiT, et al., 2023. LncRNA T376626 is a promising serum biomarker and promotes proliferation, migration, and invasion via binding to LAMC2 in triple-negative breast cancer. Gene, 860:147227.

[18]HermanAB, TsitsipatisD, GorospeM, 2022. Integrated lncRNA function upon genomic and epigenomic regulation. Mol Cell, 82(12):2252-2266.

[19]HuQS, YeYQ, ChanLC, et al., 2019. Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression. Nat Immunol, 20(7):835-851.

[20]HuY, HeY, LuoN, et al., 2023. A feedback loop between lncRNA MALAT1 and DNMT1 promotes triple-negative breast cancer stemness and tumorigenesis. Cancer Biol Ther, 24(1):2235768.

[21]JiangXG, 2014. Harnessing the immune system for the treatment of breast cancer. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 15(1):1-15.

[22]JiangYZ, LiuYR, XuXE, et al., 2016. Transcriptome analysis of triple-negative breast cancer reveals an integrated mRNA-lncRNA signature with predictive and prognostic value. Cancer Res, 76(8):2105-2114.

[23]KaushikAC, MehmoodA, WangXG, et al., 2021. Globally ncRNAs expression profiling of TNBC and screening of functional lncRNA. Front Bioeng Biotechnol, 8:523127.

[24]KnutsenE, HarrisAL, PeranderM, 2022. Expression and functions of long non-coding RNA NEAT1 and isoforms in breast cancer. Br J Cancer, 126(4):551-561.

[25]KottermanMA, SchafferDV, 2014. Engineering adeno-associated viruses for clinical gene therapy. Nat Rev Genet, 15(7):445-451.

[26]KumarP, AggarwalR, 2016. An overview of triple-negative breast cancer. Arch Gynecol Obstet, 293(2):247-269.

[27]KumarV, WestraHJ, KarjalainenJ, et al., 2013. Human disease-associated genetic variation impacts large intergenic non-coding RNA expression. PLoS Genet, 9(1):e1003201.

[28]KuschelA, SimonP, TugS, 2012. Functional regulation of HIF-1α under normoxia‍—‍is there more than post-translational regulation? J Cell Physiol, 227(2):514-524.

[29]LanFM, ZhangXD, LiHB, et al., 2021. Serum exosomal lncRNA XIST is a potential non-invasive biomarker to diagnose recurrence of triple-negative breast cancer. J Cell Mol Med, 25(16):7602-7607.

[30]LehmannBD, BauerJA, ChenX, et al., 2011. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 121(7):2750-2767.

[31]LiPP, LiRG, HuangYQ, et al., 2021. LncRNA OTUD6B-AS1 promotes paclitaxel resistance in triple negative breast cancer by regulation of miR-26a-5p/MTDH pathway-mediated autophagy and genomic instability. Aging, 13(21):24171-24191.

[32]LinAF, LiCL, XingZ, et al., 2016. The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer. Nat Cell Biol, 18(2):213-224.

[33]LinJG, ShiZH, YuZY, et al., 2018. LncRNA HIF1A-AS2 positively affects the progression and EMT formation of colorectal cancer through regulating miR-129-5p and DNMT3A. Biomed Pharmacother, 98:433-439.

[34]LiuAN, QuHJ, GongWJ, et al., 2019. LncRNA AWPPH and miRNA-21 regulates cancer cell proliferation and chemosensitivity in triple-negative breast cancer by interacting with each other. J Cell Biochem, 120(9):14860-14866.

[35]LiuM, XingLQ, LiuYJ, 2017. A three-long noncoding RNA signature as a diagnostic biomarker for differentiating between triple-negative and non-triple-negative breast cancers. Medicine, 96(9):e6222.

[36]LiuXH, SunM, NieFQ, et al., 2014. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer, 13:92.

[37]LongQ, LiH, FanY, et al., 2020. Overexpression of lncRNA TATDN1 promotes cancer cell proliferation in triple negative breast cancer by regulating miR-26b methylation. Cancer Manag Res, 12:11403-11410.

[38]LuSX, HanL, HuXY, et al., 2021. N6-methyladenosine reader IMP2 stabilizes the ZFAS1/OLA1 axis and activates the Warburg effect: implication in colorectal cancer. J Hematol Oncol, 14:188.

[39]ManjunathM, ChoudharyB, 2021. Triple-negative breast cancer: a run-through of features, classification and current therapies (Review). Oncol Lett, 22:512.

[40]ManoochehriM, BorhaniN, GerhäuserC, et al., 2023. DNA methylation biomarkers for noninvasive detection of triple-negative breast cancer using liquid biopsy. Int J Cancer, 152(5):1025-1035.

[41]MittendorfEA, ZhangH, BarriosCH, et al., 2020. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet, 396(10257):1090-1100.

[42]MouEX, WangH, 2019. LncRNA LUCAT1 facilitates tumorigenesis and metastasis of triple-negative breast cancer through modulating miR-5702. Biosci Rep, 39(9):BSR20190489.

[43]NedeljkovićM, DamjanovićA, 2019. Mechanisms of chemotherapy resistance in triple-negative breast cancer—‍how we can rise to the challenge. Cells, 8(9):957.

[44]NitzanM, Steiman-ShimonyA, AltuviaY, et al., 2014. Interactions between distant ceRNAs in regulatory networks. Biophys J, 106(10):2254-2266.

[45]PaciP, ColomboT, FarinaL, 2014. Computational analysis identifies a sponge interaction network between long non-coding RNAs and messenger RNAs in human breast cancer. BMC Syst Biol, 8:83.

[46]PingJ, HuangSY, WuJ, et al., 2021. Association between lincRNA expression and overall survival for patients with triple-negative breast cancer. Breast Cancer Res Treat, 186(3):769-777.

[47]PratA, PinedaE, AdamoB, et al., 2015. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast, 24(Suppl 2):S26-S35.

[48]QuL, HeXY, TangQ, et al., 2022. Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(10):844-862.

[49]RaoM, XuS, ZhangY, et al., 2021. Long non-coding RNA ZFAS1 promotes pancreatic cancer proliferation and metastasis by sponging miR-497-5p to regulate HMGA2 expression. Cell Death Dis, 12(10):859.

[50]SamirA, TawabRA, el TayebiHM, 2021. Long non-coding RNAs XIST and MALAT1 hijack the PD-L1 regulatory signaling pathway in breast cancer subtypes. Oncol Lett, 22(2):593.

[51]SantamaríaG, BargallóX, GanauS, et al., 2019. Multiparametric MR imaging to assess response following neoadjuvant systemic treatment in various breast cancer subtypes: comparison between different definitions of pathologic complete response. Eur J Radiol, 117:132-139.

[52]SemenzaGL, 2003. Targeting HIF-1 for cancer therapy. Nat Rev Cancer, 3(10):721-732.

[53]ShaoXC, ZhengXH, MaD, et al., 2021. Inhibition of lncRNA-NEAT1 sensitizes 5-Fu resistant cervical cancer cells through de-repressing the microRNA-34a/LDHA axis. Biosci Rep, 41(7):BSR20200533.

[54]SharmaU, BarwalTS, KhandelwalA, et al., 2021. LncRNA ZFAS1 inhibits triple-negative breast cancer by targeting STAT3. Biochimie, 182:99-107.

[55]ShenXK, XieBJ, MaZS, et al., 2015. Identification of novel long non-coding RNAs in triple-negative breast cancer. Oncotarget, 6(25):21730-21739.

[56]ShengXN, DaiHJ, DuYY, et al., 2021. LncRNA CARMN overexpression promotes prognosis and chemosensitivity of triple negative breast cancer via acting as miR143-3p host gene and inhibiting DNA replication. J Exp Clin Cancer Res, 40:205.

[57]ShiF, XiaoF, DingP, et al., 2016. Long noncoding RNA highly up-regulated in liver cancer predicts unfavorable outcome and regulates metastasis by MMPs in triple-negative breast cancer. Arch Med Res, 47(6):446-453.

[58]ShinVY, ChenJW, CheukIWY, et al., 2019. Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness. Cell Death Dis, 10(4):270.

[59]SinghDD, LeeHJ, YadavDK, 2023. Recent clinical advances on long non-coding RNAs in triple-negative breast cancer. Cells, 12(4):674.

[60]SongX, LiuZY, YuZY, 2019. LncRNA NEF is downregulated in triple negative breast cancer and correlated with poor prognosis. Acta Biochim Biophys Sin, 51(4):386-392.

[61]SunJ, LiXH, YuEQ, et al., 2021. A novel tumor suppressor ASMTL-AS1 regulates the miR-1228-3p/SOX17/β-catenin axis in triple-negative breast cancer. Diagn Pathol, 16:45.

[62]SunWD, ZuSL, ShaoGF, et al., 2021. Long non-coding DANCR targets miR-185-5p to upregulate LIM and SH3 protein 1 promoting prostate cancer via the FAK/PI3K/AKT/GSK3Β/snail pathway. J Gene Med, 23(7):e3344.

[63]SwellamM, el MagdoubHM, ShawkiMA, et al., 2021. Clinical impact of LncRNA XIST and LncRNA NEAT1 for diagnosis of high-risk group breast cancer patients. Curr Probl Cancer, 45(5):100709.

[64]TangJM, ZhongGS, ZhangHB, et al., 2018. LncRNA DANCR upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA. Cell Death Dis, 9(12):1167.

[65]TangTL, ChengYG, SheQ, et al., 2018. Long non-coding RNA TUG1 sponges miR-197 to enhance cisplatin sensitivity in triple negative breast cancer. Biomed Pharmacother, 107:338-346.

[66]TaoWY, WangCY, ZhuBF, et al., 2019. LncRNA DANCR contributes to tumor progression via targetting miR-216a-5p in breast cancer: lncRNA DANCR contributes to tumor progression. Biosci Rep, 39(4):BSR20181618.

[67]VtorushinS, DulesovaA, KrakhmalN, 2022. Luminal androgen receptor (LAR) subtype of triple-negative breast cancer: molecular, morphological, and clinical features. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(8):‍617-624.

[68]WanWJ, AoX, ChenQ, et al., 2022. METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer. Mol Cancer, 21:60.

[69]WangL, LiuDQ, WuXR, et al., 2018. Long non-coding RNA (LncRNA) RMST in triple-negative breast cancer (TNBC): expression analysis and biological roles research. J Cell Physiol, 233(10):6603-6612.

[70]WangN, HouMS, ZhanY, et al., 2019. LncRNA PTCSC3 inhibits triple-negative breast cancer cell proliferation by downregulating lncRNA H19. J Cell Biochem, 120(9):15083-15088.

[71]WangPS, ChouCH, LinCH, et al., 2018. A novel long non-coding RNA linc-ZNF469-3 promotes lung metastasis through miR-574-5p-ZEB1 axis in triple negative breast cancer. Oncogene, 37(34):4662-4678.

[72]WangR, HuangZM, QianCW, et al., 2020. LncRNA WEE2-AS1 promotes proliferation and inhibits apoptosis in triple negative breast cancer cells via regulating miR-32-5p/TOB1 axis. Biochem Biophys Res Commun, 526(4):1005-1012.

[73]WangSW, KeH, ZhangHL, et al., 2018. LncRNA MIR100HG promotes cell proliferation in triple-negative breast cancer through triplex formation with p27 loci. Cell Death Dis, 9(8):805.

[74]WangYF, ZhangGC, HanJ, 2019. HIF1A-AS2 predicts poor prognosis and regulates cell migration and invasion in triple-negative breast cancer. J Cell Biochem, 120(6):10513-10518.

[75]WongCCL, GilkesDM, ZhangHF, et al., 2011. Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc Natl Acad Sci USA, 108(39):16369-16374.

[76]XuJ, WuKJ, JiaQJ, et al., 2020. Roles of miRNA and lncRNA in triple-negative breast cancer. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(9):673-689.

[77]YangJ, MengXL, YuY, et al., 2019. LncRNA POU3F3 promotes proliferation and inhibits apoptosis of cancer cells in triple-negative breast cancer by inactivating caspase 9. Biosci Biotechnol Biochem, 83(6):1117-1123.

[78]YangX, ZhangS, HeCY, et al., 2020. METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST. Mol Cancer, 19:46.

[79]YounessRA, HafezHM, KhallafE, et al., 2019. The long noncoding RNA sONE represses triple-negative breast cancer aggressiveness through inducing the expression of miR-34a, miR-15a, miR-16, and let-7a. J Cell Physiol, 234(11):20286-20297.

[80]YuCC, LiY, ChenGP, et al., 2022. Bioactive constituents of animal-derived traditional Chinese medicinal materials for breast cancer: opportunities and challenges. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(7):547-563.

[81]ZaheerS, ShahN, MaqboolSA, et al., 2019. Estimates of past and future time trends in age-specific breast cancer incidence among women in Karachi, Pakistan: 2004‍–2025. BMC Public Health, 19:1001.

[82]ZhangGX, LiHL, SunRM, et al., 2019. Long non-coding RNA ZEB2-AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple-negative breast cancer by epigenetically activating ZEB2. J Cell Mol Med, 23(5):3271-3279.

[83]ZhangKM, LiuP, TangHL, et al., 2018. AFAP1-AS1 promotes epithelial-mesenchymal transition and tumorigenesis through Wnt/β‍-catenin signaling pathway in triple-negative breast cancer. Front Pharmacol, 9:1248.

[84]ZhangM, WengWW, ZhangQY, et al., 2018. The lncRNA NEAT1 activates Wnt/β‍-catenin signaling and promotes colorectal cancer progression via interacting with DDX5. J Hematol Oncol, 11:113.

[85]ZhangYD, ZhangHW, KangHQ, et al., 2019. Knockdown of long non-coding RNA HOST2 inhibits the proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis. Int J Mol Med, 43(2):1049-1057.

[86]ZhaoS, ZuoWJ, ShaoZM, et al., 2020. Molecular subtypes and precision treatment of triple-negative breast cancer. Ann Transl Med, 8(7):499.

[87]ZhengBH, HeZX, ZhangJ, et al., 2021. The biological function of TUSC7/miR-1224-3p axis in triple-negative breast cancer. Cancer Manag Res, 13:5763-5774.

[88]ZhengSP, LiMQ, MiaoKK, et al., 2020. LncRNA GAS5-promoted apoptosis in triple-negative breast cancer by targeting miR-378a-5p/SUFU signaling. J Cell Biochem, 121(3):2225-2235.

[89]ZhengSQ, YangL, ZouYT, et al., 2020. Long non-coding RNA HUMT hypomethylation promotes lymphangiogenesis and metastasis via activating FOXK1 transcription in triple-negative breast cancer. J Hematol Oncol, 13:17.

[90]ZhuH, ZhengT, YuJ, et al., 2018. LncRNA XIST accelerates cervical cancer progression via upregulating Fus through competitively binding with miR-200a. Biomed Pharmacother, 105:789-797.

[91]ZhuYM, JinL, ShiRH, et al., 2022. The long noncoding RNA glycoLINC assembles a lower glycolytic metabolon to promote glycolysis. Mol Cell, 82(3):542-554.e6.

[92]ZuoYG, LiY, ZhouZY, et al., 2017. Long non-coding RNA MALAT1 promotes proliferation and invasion via targeting miR-129-5p in triple-negative breast cancer. Biomed Pharmacother, 95:922-928.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE