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中华乳腺病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (04) : 238 -242. doi: 10.3877/cma.j.issn.1674-0807.2025.04.008

综述

RNA m6A修饰在乳腺癌进展及化疗耐药中的研究进展
孙宇佳1,3, 张少宁1,3, 贾绍昌2, 奥旭东3,()   
  1. 1 010110 呼和浩特,内蒙古医科大学研究生院
    2 210002 南京,解放军东部战区总医院全军肿瘤中心生物治疗科
    3 010110 呼和浩特,北京大学肿瘤医院内蒙古医院肿瘤生物治疗中心
  • 收稿日期:2024-11-18 出版日期:2025-08-01
  • 通信作者: 奥旭东
  • 基金资助:
    内蒙古自治区公立医院科研联合基金科技项目(2023GLLH0128); 内蒙古自治区卫生健康科技计划项目(202201361); 内蒙古医科大学面上资助项目(YKD2022MS012)

Role of RNA m6A modification in breast cancer progression and chemoresistance

Yujia Sun, Shaoning Zhang, Shaochang Jia   

  • Received:2024-11-18 Published:2025-08-01
引用本文:

孙宇佳, 张少宁, 贾绍昌, 奥旭东. RNA m6A修饰在乳腺癌进展及化疗耐药中的研究进展[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(04): 238-242.

Yujia Sun, Shaoning Zhang, Shaochang Jia. Role of RNA m6A modification in breast cancer progression and chemoresistance[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2025, 19(04): 238-242.

N6-甲基腺苷(m6A)作为真核生物RNA内部修饰的普遍且保守形式,近年来在乳腺癌研究中引起了广泛关注。m6A修饰由甲基转移酶催化生成,去甲基化酶负责清除,并由特定结合蛋白识别调控,维持其动态平衡。这一修饰在乳腺癌细胞的增殖、迁移、侵袭及化疗耐药等多个生物学过程中发挥重要作用。本文总结了m6A修饰在乳腺癌发展中的分子机制及其功能,并深入探讨了其在化疗耐药中的潜在作用,旨在为乳腺癌临床治疗策略的创新提供科学依据,提升患者的生存率和生活质量。

图1 真核细胞中常见的RNA m6A修饰相关蛋白定位及其功能 注:CBLL1为Cbl原癌基因样蛋白1;VIRMA为病毒样m6A甲基转移酶相关蛋白;RBM15/15B为RNA结合基序蛋白15/15B;METTL为甲基转移酶样蛋白;ZC3H13为含 CCCH 型锌指蛋白13;WTAP为肾母细胞瘤1相关蛋白;ALKBH5为烷基化修复同源蛋白5;FTO为脂肪质量和肥胖相关基因;HNRNPC为异质核糖核蛋白C;YTHDC为YTH 结构域包含蛋白;HNRNPA2B1为异质核糖核蛋白 A2/B1;YTHDF为YTH 结构域家族蛋白;IGF2BP为胰岛素样生长因子 2 mRNA 结合蛋白;FMR1为脆性X信使核糖核蛋白1;m6A为N6-甲基腺苷
[1]
Bianchini GBalko JMMayer IA,et al. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease[J].Nat Rev Clin Oncol201613(11): 674-690.
[2]
Chen YLin YShu Y,et al. Interaction between N6-methyladenosine (m6A) modification and noncoding RNAs in cancer[J].Mol Cancer202019(1): 94.
[3]
Siegel RLGiaquinto ANJemal A. Cancer statistics,2024[J].CA Cancer J Clin202474(1): 12-49.
[4]
Bray FLaversanne MSung H,et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin202474(3): 229-263.
[5]
Coles CEEarl HAnderson BO,et al. The lancet breast cancer commission[J].Lancet2024403(10439): 1895-1950.
[6]
Huang HWeng HChen J. m6A modification in coding and non-coding RNAs: roles and therapeutic implications in cancer[J].Cancer Cell202037(3): 270-288.
[7]
Petri BJKlinge CM. m6A readers,writers,erasers,and the m6A epitranscriptome in breast cancer[J].J Mol Endocrinol202270(2): e220110.
[8]
Liu CYang ZLi R,et al. Potential roles of N6-methyladenosine (m6A) in immune cells[J].J Transl Med202119(1): 251.
[9]
Deng XSu RWeng H,et al. RNA N6-methyladenosine modification in cancers: current status and perspectives[J].Cell Res201828(5): 507-517.
[10]
Fan SWang L. N6-methyladenosine-regulated LINC00675 suppress the proliferation,migration and invasion of breast cancer cells via inhibiting miR-513b-5p[J].Bioengineered202112(2): 10690-10702.
[11]
Guo YFeng L. N6-methyladenosine-mediated upregulation of LINC00520 accelerates breast cancer progression via regulating miR-577/POSTN axis and downstream ILK/AKT/mTOR signaling pathway[J].Arch Biochem Biophys2022729: 109381.
[12]
Xu YSong MHong Z,et al. The N6-methyladenosine METTL3 regulates tumorigenesis and glycolysis by mediating m6A methylation of the tumor suppressor LATS1 in breast cancer[J].J Exp Clin Cancer Res202342(1): 10.
[13]
Wan WAo XChen Q,et al. METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer[J].Mol Cancer202221(1): 60.
[14]
Zhao CLing XXia Y,et al. The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition,migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis[J].Cancer Cell Int202121(1): 441.
[15]
Ren SZhang YYang X,et al. N6-methyladenine-induced LINC00667 promoted breast cancer progression through m6A/KIAA1429 positive feedback loop[J].Bioengineered202213(5): 13462-13473.
[16]
Chen CWang YLi Y,et al. VIRMA facilitates triple-negative breast cancer progression via increasing m6A-dependent KIF15 expression[J]. Discov Med202335(178): 787-795.
[17]
Qian JYGao JSun X,et al. KIAA1429 acts as an oncogenic factor in breast cancer by regulating CDK1 in an N6-methyladenosine-independent manner[J].Oncogene201938(33): 6123-6141.
[18]
Niu YLin ZWan A,et al. RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3[J].Mol Cancer201918(1): 46.
[19]
Yi DXu FWang R,et al. Deciphering the map of METTL14‐mediated lncRNA m6A modification at the transcriptome‐wide level in breast cancer[J].J Clin Lab Anal202236(12): e24754.
[20]
Lv CGCheng YZhang L,et al. EXOSC2 mediates the pro-tumor role of WTAP in breast cancer cells via activating the Wnt/β-catenin signal[J].Mol Biotechnol202466(9): 2569-2582.
[21]
Ou BLiu YYang X,et al. C5aR1-positive neutrophils promote breast cancer glycolysis through WTAP-dependent m6A methylation of ENO1[J].Cell Death Dis202112(8): 737.
[22]
Park SHJu JSWoo H,et al. The m6A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism[J].Exp Mol Med202456(6): 1373-1387.
[23]
Zheng FDu FQian H,et al. Expression and clinical prognostic value of m6A RNA methylation modification in breast cancer[J].Biomark Res20219(1): 28.
[24]
Ou BLiu YGao Z,et al. Senescent neutrophils-derived exosomal piRNA-17560 promotes chemoresistance and EMT of breast cancer via FTO-mediated m6A demethylation[J].Cell Death Dis202213(10): 905.
[25]
Yan YMa JChen Q,et al. GAS5 regulated by FTO-mediated m6A modification suppresses cell proliferation via the IGF2BP2/QKI axis in breast cancer[J].Discov Oncol202415(1): 182.
[26]
Zhang CSamanta DLu H,et al. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA[J].Proc Natl Acad Sci USA2016113(14): E2047-E2056.
[27]
Anita RParamasivam APriyadharsini JV,et al. The m6A readers YTHDF1 and YTHDF3 aberrations associated with metastasis and predict poor prognosis in breast cancer patients[J].Am J Cancer Res202010(8): 2546-2554.
[28]
Chen HYu YYang M,et al. YTHDF1 promotes breast cancer progression by facilitating FOXM1 translation in an m6A-dependent manner[J].Cell Biosci202212(1): 19.
[29]
Lin YJin XNie Q,et al. YTHDF3 facilitates triple-negative breast cancer progression and metastasis by stabilizing ZEB1 mRNA in an m6A-dependent manner[J].Ann Transl Med202210(2) :83.
[30]
Li XZhang KJHu Y,et al. YTHDF2 regulates cell growth and cycle by facilitating KDM1A mRNA stability[J].Am J Pathol2023193(4): 442-455.
[31]
Shi JZhang QYin X,et al. Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner[J].Int J Biol Sci202319(2): 449-464.
[32]
Zhong SLin ZChen H,et al. The m6A-related gene signature for predicting the prognosis of breast cancer[J].Peer J20219: e11561.
[33]
Zhang XShi LSun HD,et al. IGF2BP3 mediates the mRNA degradation of NF1 to promote triple‐negative breast cancer progression via an m6A‐dependent manner[J].Clin Transl Med202313(9): e1427.
[34]
Wu YZhao WLiu Y,et al. Function of HNRNPC in breast cancer cells by controlling the dsRNA‐induced interferon response[J].EMBO J201837(23): e99017.
[35]
Xu WHuang ZXiao Y,et al. HNRNPC promotes estrogen receptor‐positive breast cancer cell cycle by stabilizing WDR77 mRNA in an m6A‐dependent manner[J].Mol Carcinog202463(5): 859-873.
[36]
Lian BYan SLi J,et al. HNRNPC promotes collagen fiber alignment and immune evasion in breast cancer via activation of the VIRMA-mediated TFAP2A/DDR1 axis[J].Mol Med202329(1): 103.
[37]
Ayoufu AYi LTuersuntuoheti M,et al. HNRNPA2B1 is a potential biomarker of breast cancer related to prognosis and immune infiltration[J].Aging (Albany NY)202315(17): 8712-8728.
[38]
Jin TYang LChang C,et al. HnRNPA2B1 ISGylation regulates m6A‐tagged mRNA selective export via ALYREF/NXF1 complex to foster breast cancer development[J].Adv Sci (Weinh)202411(24): e2307639.
[39]
Li SJiang FChen F,et al. Effect of m6A methyltransferase METTL3‐mediated MALAT1/E2F1/AGR2 axis on adriamycin resistance in breast cancer[J].J Biochem Mol Toxicol202236(1): e22922.
[40]
Zhou SSheng LZhang L,et al. METTL3/IGF2BP3-regulated m6A modification of HYOU1 confers doxorubicin resistance in breast cancer[J].Biochim Biophys Acta Gen Subj20241868(3): 130542.
[41]
Wang JXu JZheng J. A1BG-AS1 promotes adriamycin resistance of breast cancer by recruiting IGF2BP2 to upregulate ABCB1 in an m6A-dependent manner[J].Sci Rep202313(1): 20730.
[42]
Wei LBai YNa L,et al. E2F3 induces DNA damage repair,stem-like properties and therapy resistance in breast cancer[J].Biochim Biophys Acta Mol Basis Dis20231869(8): 166816.
[43]
Liu XLi PHuang Y,et al. m6A demethylase ALKBH5 regulates FOXO1 mRNA stability and chemoresistance in triple-negative breast cancer[J].Redox Biol202469: 102993.
[44]
Jing LLan LMingxin Z,et al. METTL3/LINC00662/miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer[J].Sci Rep202212(1): 16715.
[45]
Ou XTan YXie J,et al. Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer[J].Drug Resist Updat202473: 101063.
[46]
Gao LQiao LLi Y,et al. ALKBH5 regulates paclitaxel resistance in NSCLC via inhibiting CEMIP-mediated EMT[J].Toxicol Appl Pharmacol2024483: 116807.
[47]
Zhao CZhang FTian Y,et al. m6A reader IGF2BP1 reduces the sensitivity of nasopharyngeal carcinoma cells to Taxol by upregulation of AKT2[J].Anticancer Drugs202435(6): 501-511.
[48]
Zhu MLiu YSong Y,et al. The role of METTL3-mediated N6-methyladenosine (m6A) of JPH2 mRNA in cyclophosphamide-induced cardiotoxicity[J].Front Cardiovasc Med20218: 763469.
[49]
Zhang KZhang TYang Y,et al. N6-methyladenosine-mediated LDHA induction potentiates chemoresistance of colorectal cancer cells through metabolic reprogramming[J].Theranostics202212(10): 4802-4817.
[50]
Sun YDong DXia Y,et al. YTHDF1 promotes breast cancer cell growth,DNA damage repair and chemoresistance[J].Cell Death Dis202213(3): 230.
[51]
Yu HYang XTang J,et al. ALKBH5 inhibited cell proliferation and sensitized bladder cancer cells to cisplatin by m6A-CK2α-mediated glycolysis[J].Mol Ther Nucleic Acids202123: 27-41.
[52]
Wei WSun JZhang H,et al. Circ0008399 interaction with WTAP promotes assembly and activity of the m6A methyltransferase complex and promotes cisplatin resistance in bladder cancer[J].Cancer Res202181(24): 6142-6156.
[53]
Wei JYin YZhou J,et al. METTL3 potentiates resistance to cisplatin through m6A modification of TFAP2C in seminoma[J].J Cell Mol Med202024(19): 11366-11380.
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