国际口腔医学杂志

国际口腔医学杂志 ›› 2026, Vol. 53 ›› Issue (3): 441-448.doi: 10.7518/gjkq.2026220

• 综述 • 上一篇    

微小RNA-143/145基因簇在口腔鳞状细胞癌细胞信号通路调控中作用的研究进展

郭文迪1,2(),齐鲁2,3,王星1,2()   

  1. 1.新疆医科大学第一附属医院（附属口腔医院）口腔修复种植科 乌鲁木齐 830054
    2.新疆维吾尔自治区口腔医学研究所 乌鲁木齐 830054
    3.新疆医科大学第二附属医院口腔科 乌鲁木齐 830063
  • 收稿日期:2024-12-04 修回日期:2025-03-18 出版日期:2026-05-01 发布日期:2026-04-24
  • 通讯作者: 王星
  • 作者简介:郭文迪，硕士，Email：iuwdjiu@163.com

Research progress in the regulatory role of microRNA-143/145 gene cluster in signaling pathways of oral squamous cell carcinoma

Wendi Guo1,2(),Lu Qi2,3,Xing Wang1,2()   

  1. 1.Dept. of Prosthodontics and Implant Dentistry, the First Affiliated Hospital of Xinjiang Medical University (Affiliated Stomatology Hospital), Urumqi 830054, China
    2.Stomatology Research Institute of Xinjiang Uygur Autonomous Region, Urumqi 830054, China
    3.Dept. of Stomatology, the Second Affiliated Hospital of Xinjiang Medical University, Urumqi 830063, China
  • Received:2024-12-04 Revised:2025-03-18 Online:2026-05-01 Published:2026-04-24
  • Contact: Xing Wang

RichHTML

3

PDF (PC)

8

摘要：

口腔鳞状细胞癌（OSCC）是口腔颌面部最常见的恶性肿瘤，由于缺乏特异性治疗手段，传统的手术切除仍是主要的治疗策略，但随之而来的口腔颌面部缺损对患者的生活质量造成了严重影响，因此阐明调控OSCC发生发展的分子机制愈显必要。越来越多的报道提示微小RNA（miRNA）-143和miRNA-145在OSCC中异常表达，并深入参与其发生演进。研究miRNA-143和miRNA-145在OSCC中的表达及靶基因调控作用有助于进一步阐明其分子机制，明确二者作为生物标志物和分子靶标的价值，从而为OSCC临床诊疗提供新思路。

关键词: 微小RNA-143, 微小RNA-145, 口腔鳞状细胞癌, 信号通路, 靶基因

Abstract:

Oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm in the oral and maxillofacial region. Traditional surgical excision remains the primary treatment because of the lack of specific therapeutic approaches. However, the resultant oral and maxillofacial defects severely impact patients’ quality of life. Therefore, elucidating the molecular mechanisms regulating OSCC development is crucial. microRNA (miRNA)-143 and miRNA-145 are aberrantly expressed in OSCC and significantly participate in its pathogenesis. Studying the expression and target gene regulation of miRNA-143 and miRNA-145 in OSCC may help clarify its molecular mechanisms, confirm their value as biomarkers and molecular targets, and provide new insights for clinical diagnosis and treatment.

Key words: microRNA-143, microRNA-145, oral squamous cell carcinoma, signaling pathway, target gene

中图分类号: 

  • Q257

图 1

miRNA的合成"

图2

miRNA的功能调控"

表 1

miR-143、miR-145在OSCC中的差异表达"

研究者时间/年来源方法miRNA表达
Yu等[26]20093例OSCC动物模型和3例正常动物模型qRT-PCRmiR-143、miR-145下调
Gao等[30]201362例OSCC组织样本qRT-PCRmiR-145下调
邵渊等[31]2014口腔癌细胞株CAL27qRT-PCRmiR-145下调
Wang等[28]2016暴露于槟榔碱的口腔上皮细胞株（AOE）qRT-PCRmiR-145下调
Sun等[25]201715例OSCC组织样本和15例正常口腔黏膜组织样本qRT-PCRmiR-143下调
Mesgarzadeh等[24]2019口腔癌细胞株HN-5qRT-PCRmiR-143下调
Singh等[27]202350例OSCC组织样本和20例正常口腔黏膜组织样本qRT-PCRmiR-145下调
刘岚等[29]2024102例OSCC组织样本和86例正常口腔黏膜组织样本qPCRmiR-145下调

图 3

miR-143、miR-145对下游靶基因的调控"

图 4

miR-143、miR-145的上游调控"

[1] Clements K, McMahon AD, Bhatti L, et al. Incidence trends in head and neck cancer subsites: a national population-based study (2001-2020)[J]. Clin Otolaryngol, 2025, 50(3): 474-484.
[2] 孙荣寅, 李舜航, 韩翔翔, 等. 1990-2019年中国口腔癌发病率年龄-时期-队列分析及2020-2049年趋势预测[J]. 中国肿瘤, 2023, 32(10): 753-759.
Sun RY, Li SH, Han XX, et al. Age-period-cohort analysis from 1990 to 2019 and prediction of oral cancer incidence from 2020 to 2049 in China[J]. China Cancer, 2023, 32(10): 753-759.
[3] Griner SB, Digbeu B, Farris AN, et al. Oral cavity and oropharyngeal cancers in Texas: examining incidence rates in dental health professional shortage a-reas[J]. Cancer Causes Control, 2025, 36(5): 509-520.
[4] Chamoli A, Gosavi AS, Shirwadkar UP, et al. Overview of oral cavity squamous cell carcinoma: risk factors, mechanisms, and diagnostics[J]. Oral Oncol, 2021, 121: 105451.
[5] 李麟, 王静波, 易俊林. 多学科综合治疗新模式下口腔癌放射治疗的进展与挑战[J]. 中国肿瘤临床, 2024, 51(19): 980-987.
Li L, Wang JB, Yi JL. Progress and challenges of radiotherapy for oral cancer under the new mode of multidisciplinary treatment[J]. Chin J Clin Oncol, 2024, 51(19): 980-987.
[6] Howard A, Agrawal N, Gooi Z. Lip and oral cavity squamous cell carcinoma[J]. Hematol Oncol Clin North Am, 2021, 35(5): 895-911.
[7] Zhou R, Chen Z, Cai Y, et al. The simultaneous miR-155-5p overexpression and miR-223-3p inhibition can activate pEMT in oral squamous cell carcinoma[J]. J Appl Oral Sci, 2024, 32: e20240215.
[8] Kushwaha S, Goel A, Singh AV. Serum microRNA biomarker expression in HIV and TB: a concise overview[J]. Infect Disord Drug Targets, 2025, 25(4): e18715265305638.
[9] Ma X, Yang R, Li H, et al. Role of exosomes in the communication and treatment between OSCC and normal cells[J]. Heliyon, 2024, 10(7): e28148.
[10] Shah VN, Neumeier J, Huberdeau MQ, et al. Casein kinase 1 and 2 phosphorylate Argonaute proteins to regulate miRNA-mediated gene silencing[J]. EMBO Rep, 2023, 24(11): e57250.
[11] Bayat Z, Mazaheri T, Farhadifard H, et al. Mechanisms involved in therapeutic effects of scutellaria baicalensis georgi in oral squamous cell carcinoma based on systems biology and structural bioinformatics approaches[J]. Biomed Res Int, 2024, 2024: 1236910.
[12] 南晓旭, 贺婵娟, 刘涵, 等. FOXO转录因子在口腔鳞状细胞癌信号通路中的作用及靶向药物治疗的研究进展[J]. 四川医学, 2023, 44(7): 752-756.
Nan XX, He CJ, Liu H, et al. The role of FOXO transcription factors in the signaling pathways of oral squamous cell carcinoma and advances in targeted drug therapy[J]. Sichuan Med J, 2023, 44(7): 752-756.
[13] 刘卓炫. 基于生物信息学分析口腔鳞状细胞癌ceRNA调控网络的构建[D]. 广州: 南方医科大学, 2020.
Liu ZX. Construsction of ceRNA network in oral squamous cell carcinoma based on bioinformatics[D]. Guangzhou: Southern Medical University, 2020.
[14] 赵孝亮, 李君艳, 陈国荣. miRNA在恶性肿瘤诊断中的作用[J]. 河南大学学报(自然科学版), 2023, 53(5): 584-589.
Zhao XL, Li JY, Chen GR. The role of miRNA in the diagnosis of malignant neoplasms[J]. J Henan Univ (Nat Sci), 2023, 53(5): 584-589.
[15] Sevim Ç, Ozkaraca M, Kara M, et al. Exploring the anti‑inflammatory activity of boron compounds through the miR‑21/PTEN/AKT pathway in cecal ligation and puncture‑induced sepsis[J]. Mol Med Rep, 2025, 31(2): 52.
[16] Adereh A, Amini P, Fateh A, et al. Loc646329 sponges miR-21 to reduce RAS/MAP kinase signa-ling pathway in oral squamous cell carcinoma (OSCC) [J]. Naunyn Schmiedebergs Arch Pharmacol, 2024. doi: 10.1007/s00210-024-03671-x .
doi: 10.1007/s00210-024-03671-x
[17] 王一霖, 滕亮, 王中志, 等. miR-155-5p靶向核因子κB抑制蛋白E在人单核巨噬细胞抗新生隐球菌免疫反应中的机制研究[J]. 中国感染与化疗杂志, 2019, 19(5): 542-547.
Wang YL, Teng L, Wang ZZ, et al. Mechanistic study on the role of miR-155-5p targeting IKBKE in THP-1 cellsassociated immune response induced by Cryptococcus neoformans [J]. Chin J Infect Chemother, 2019, 19(5): 542-547.
[18] Tao Y, Ai R, Hao Y, et al. Role of miR-155 in immune regulation and its relevance in oral lichen planus[J]. Exp Ther Med, 2019, 17(1): 575-586.
[19] Findeiss E, Schwarz SC, Evsyukov V, et al. Comprehensive miRNome-wide profiling in a neuronal cell model of synucleinopathy implies involvement of cell cycle genes[J]. Front Cell Dev Biol, 2021, 9: 561086.
[20] Michael MZ, O’ Connor SM, van Holst Pellekaan NG, et al. Reduced accumulation of specific microRNAs in colorectal neoplasia[J]. Mol Cancer Res, 2003, 1(12): 882-891.
[21] Pilala KM, Papadimitriou MA, Panoutsopoulou K, et al. Epigenetic regulation of MIR145 core promo-ter controls miR-143/145 cluster in bladder cancer progression and treatment outcome[J]. Mol Ther Nucleic Acids, 2022, 30: 311-322.
[22] Wu X, Han Y, Liu F, et al. Downregulations of miR-449a and miR-145-5p act as prognostic biomarkers for endometrial cancer[J]. J Comput Biol, 2020, 27(5): 834-844.
[23] Zhao J, Zuo W, Zhang Y, et al. The polymorphism rs4705342 in the promoter of miR-143/145 is rela-ted to the risk of epithelial ovarian cancer and patient prognosis[J]. Front Oncol, 2023, 13: 1122284.
[24] Mesgarzadeh AH, Aali M, Farhadi F, et al. Transfection of microRNA-143 mimic could inhibit migration of HN-5 cells through down-regulating of metastatic genes[J]. Gene, 2019, 716: 144033.
[25] Sun X, Zhang L. MicroRNA-143 suppresses oral squamous cell carcinoma cell growth, invasion and glucose metabolism through targeting hexokinase 2[J]. Biosci Rep, 2017, 37(3): BSR20160404.
[26] Yu T, Wang XY, Gong RG, et al. The expression profile of microRNAs in a model of 7,12-dimethyl-benz[a]anthrance-induced oral carcinogenesis in Sy-rian hamster[J]. J Exp Clin Cancer Res, 2009, 28(1): 64.
[27] Singh A, Khan DU, Singh P, et al. Prognostic utility of microRNA-145 and CD 133 in oral squamous cell carcinoma: a pilot study from Northern India[J]. J Oral Biol Craniofac Res, 2023, 13(2): 92-95.
[28] Wang TY, Peng CY, Lee SS, et al. Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline[J]. Oncotarget, 2016, 7(51): 84072-84081.
[29] 刘岚, 于雪, 崔敬雅, 等. 血清miR-145和miR-195在OSCC患者中的表达及其与颈部淋巴结转移的关系分析[J]. 国际检验医学杂志, 2024, 45(4): 452-456.
Liu L, Yu X, Cui JY, et al. Expression of serum miR-145 and miR-195 in OSCC patients and their relationship with cervical lymph node metastasis[J]. Int J Lab Med, 2024, 45(4): 452-456.
[30] Gao L, Ren W, Chang S, et al. Downregulation of miR-145 expression in oral squamous cell carcinomas and its clinical significance[J]. Onkologie, 2013, 36(4): 194-199.
[31] 邵渊, 白艳霞, 权芳, 等. 上调MiR-145的表达对口腔癌细胞CAL27生物学特性的影响[J]. 西安交通大学学报(医学版), 2014, 35(4): 533-536.
Shao Y, Bai YX, Quan F, et al. Effects of up-regulation MiR-145 expression on biological characteristics of human oral carcinoma cell line CAL27[J]. J Xi’an Jiaotong Univ (Med Sci), 2014, 35(4): 533-536.
[32] Manikandan M, Deva Magendhra Rao AK, Arunkumar G, et al. Down regulation of miR-34a and miR-143 may indirectly inhibit p53 in oral squamous cell carcinoma: a pilot study[J]. Asian Pac J Cancer Prev, 2015, 16(17): 7619-7625.
[33] Xu P, Li Y, Yang S, et al. Micro-ribonucleic acid 143 (MiR-143) inhibits oral squamous cell carcinoma (OSCC) cell migration and invasion by downregulation of phospho-c-Met through targeting CD44 v3[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2015, 120(1): 43-51.
[34] Yu L, Shao X, Huo L, et al. Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes cell proliferation and migration by regulating miR-143-3p and MAGE family member A9 (MAGEA9) in oral squamous cell carcinoma[J]. Med Sci Monit, 2020, 26: e924187.
[35] Bufalino A, Cervigne NK, de Oliveira CE, et al. Low miR-143/miR-145 cluster levels induce activin a overexpression in oral squamous cell carcinomas, which contributes to poor prognosis[J]. PLoS One, 2015, 10(8): e0136599.
[36] Shao Y, Qu Y, Dang S, et al. MiR-145 inhibits oral squamous cell carcinoma (OSCC) cell growth by targeting c-Myc and Cdk6[J]. Cancer Cell Int, 2013, 13(1): 51.
[37] 冯素亚, 郭佳, 路学文. 微小RNA-145-5p靶向抑制同源形成素样蛋白2基因介导Notch信号通路对口腔鳞状细胞癌细胞增殖、凋亡的调控机制[J]. 成都医学院学报, 2020, 15(2): 208-214.
Feng SY, Guo J, Lu XW. Study on mechanism of the targeted inhibition of the fmnl2 mediated notch signaling pathway by microRNA-145-5p in regula-ting the proliferation and apoptosis of oral squamous cell carcinoma cells[J]. J Chengdu Med Coll, 2020, 15(2): 208-214.
[38] 郭芳, 黄硕. miR-145抑制口腔鳞状细胞癌Tca-8113细胞增殖活性及其与CDK6的靶向关系[J]. 山西医科大学学报, 2014, 45(7): 576-580.
Guo F, Huang S. Inhibitive effect of miR-145 on the proliferation of oral squamous cell carcinoma cell line Tca-8113 and its relationship with the targeting CDK6[J]. J Shanxi Med Univ, 2014, 45(7): 576-580.
[39] 陆伟, 王永武, 淦岷, 等. LncRNA CCAT2/miR-145/p70S6K1分子轴调控口腔鳞癌细胞侵袭转移[J]. 中国现代医生, 2020, 58(30): 53-57, 193.
Lu W, Wang YW, Gan M, et al. LncRNA CCAT2/miR-145/p70S6K1 molecular axis regulates invasion and metastasis of oral squamous cell carcinoma[J]. China Modern Doc, 2020, 58(30): 53-57, 193.
[40] 赵微, 李润滋, 张雨, 等. miR-145-5p对口腔鳞癌细胞增殖的调控作用及其机制[J]. 成都医学院学报, 2024, 19(2): 225-230.
Zhao W, Li RZ, Zhang Y, et al. Regulation of miR-145-5p on the proliferation of oral squamous cell carcinoma cells and its mechanism[J]. J Chengdu Med Coll, 2024, 19(2): 225-230.
[41] Wang S, Li W, Yang L, et al. CircPVT1 facilitates the progression of oral squamous cell carcinoma by regulating miR-143-3p/SLC7A11 axis through MAPK signaling pathway[J]. Funct Integr Geno-mics, 2022, 22(5): 891-903.
[42] 马稔秋, 崔丽娟, 杜炜. LINC00705通过调控miR-143-3p影响口腔鳞癌细胞增殖及转移能力的探究[J]. 实用口腔医学杂志, 2021, 37(4): 472-476.
Ma RQ, Cui LJ, Du W. The effects of LINC00705 on the proliferation and metastasis of oral squamous cell carcinoma cells by regulating miR-143-3p[J]. J Pract Stomatol, 2021, 37(4): 472-476.
[43] Ai Y, Song J, Wei H, et al. circ_0001461 promotes oral squamous cell carcinoma progression through miR-145/TLR4/NF‑κB axis[J]. Biochem Biophys Res Commun, 2021, 566: 108-114.
[44] Lu Q, Che H, Che Y, et al. CircZNF236 facilitates malignant progression in oral squamous cell carcinoma by sequestering miR-145-5p[J]. Clin Transl Oncol, 2023, 25(6): 1690-1701.
[45] Zhou J, Jin S. Circ_0058063 contributed to oral squamous cell carcinoma development by sponging miR-145 and regulating PI3K/AKT pathway[J]. Mol Biotechnol, 2023, 65(12): 2049-2060.
[46] Arunkumar G, Deva Magendhra Rao AK, Manikandan M, et al. Expression profiling of long non-co-ding RNA identifies linc-RoR as a prognostic biomarker in oral cancer[J]. Tumour Biol, 2017, 39(4): 1010428317698366.
[47] Shademan B, Karamad V, Nourazarian A, et al. MicroRNAs as targets for cancer diagnosis: interests and limitations[J]. Adv Pharm Bull, 2023, 13(3): 435-445.
[48] Hill M, Tran N. miRNA interplay: mechanisms and consequences in cancer[J]. Dis Model Mech, 2021, 14(4): dmm047662.
[49] He B, Zhao Z, Cai Q, et al. miRNA-based biomar-kers, therapies, and resistance in cancer[J]. Int J Biol Sci, 2020, 16(14): 2628-2647.
[50] Valihrach L, Androvic P, Kubista M. Circulating miRNA analysis for cancer diagnostics and therapy[J]. Mol Aspects Med, 2020, 72: 100825.
[51] Ghosh RD, Pattatheyil A, Roychoudhury S. Functional landscape of dysregulated microRNAs in oral squamous cell carcinoma: clinical implications[J]. Front Oncol, 2020, 10: 619.
[52] Menini M, De Giovanni E, Bagnasco F, et al. Salivary micro-RNA and oral squamous cell carcinoma: a systematic review[J]. J Pers Med, 2021, 11(2): 101.
[53] Zhang HY, Ma JH. miR-105 promotes the progression and predicts the prognosis for oral squamous cell carcinoma (OSCC)[J]. Cancer Manag Res, 2020, 12: 11491-11499.
[54] Jakob M, Mattes LM, Unger K, et al. Human microRNA-182-5p and kinectin 1: potential biomar-kers for prognosis in oral squamous cell carcinoma[J]. Head Neck, 2021, 43(12): 3707-3719.
[55] Shen Q, Xiong P, Yang D, et al. Downregulated microRNA-149-3p triggers malignant development and predicts worse prognosis in oral squamous cell carcinoma[J]. Arch Oral Biol, 2022, 134: 105336.
[56] Sarode GS, Sarode SC, Maniyar N, et al. Oral cancer databases: a comprehensive review[J]. J Oral Pathol Med, 2018, 47(6): 547-556.
[57] Lin X, Wu W, Ying Y, et al. MicroRNA-31: a pivo-tal oncogenic factor in oral squamous cell carcinoma[J]. Cell Death Discov, 2022, 8(1): 140.
[58] 张伟锋, 舒艳, 万择秋. 血清miRNA液体活检在早期卵巢癌诊断中的临床价值[J]. 中国现代医生, 2024, 62(16): 42-45.
Zhang WF, Shu Y, Wan ZQ. Clinical value of serum miRNA liquid biopsy in the diagnosis of early ovarian cancer[J]. China Modern Doc, 2024, 62(16): 42-45.
[1] 林健辉,蒋文芮,韩瑞,刘新伟,张靓,周美云,徐锦程. 葫芦素B通过核因子E2相关因子2/溶质载体家族7成员11/谷胱甘肽过氧化物酶4信号通路诱导舌鳞状细胞癌CAL-27细胞铁死亡[J]. 国际口腔医学杂志, 2026, 53(3): 352-361.
[2] 付莹欣,顾智玉,周灵,林龙,林静,刘云坤. 乳酸及乳酸化修饰在口腔鳞状细胞癌中的研究进展[J]. 国际口腔医学杂志, 2026, 53(2): 247-256.
[3] 张琳涵,汤亚玲. 拉曼光谱技术在口腔鳞状细胞癌和口腔潜在恶性疾病诊断和治疗中的应用进展[J]. 国际口腔医学杂志, 2026, 53(1): 107-115.
[4] 薛丽丽,陈帅,闫冰. Yes相关蛋白作为机械传导效应分子在口腔及其他系统非肿瘤性疾病发生发展中的作用[J]. 国际口腔医学杂志, 2025, 52(5): 691-698.
[5] 姚曼曼,仇永乐,刘铁军,路月亭,路华林,尚宏悦,董博. 微小RNA200a/141-信号转导和转录激活因子4轴在口腔鳞状细胞癌进展中的作用研究[J]. 国际口腔医学杂志, 2025, 52(4): 473-483.
[6] 赵家硕,张艳艳,刘飞,沈颉飞. 神经肽参与调控神经病理性疼痛机制的研究进展[J]. 国际口腔医学杂志, 2025, 52(4): 498-506.
[7] 王倩,彭晖,章礼玉,杨宗澄,王雨琪,潘宇,周瑜. 影像组学在口腔鳞状细胞癌颈部淋巴结转移方面的应用进展[J]. 国际口腔医学杂志, 2025, 52(4): 507-513.
[8] 李熠洁,原振英,李明. 支链氨基酸转氨酶1在口腔鳞状细胞癌中的表达及其功能研究[J]. 国际口腔医学杂志, 2025, 52(3): 358-365.
[9] 买克里亚·艾克帕尔,买买提吐逊·吐尔地. 吲哚菁绿荧光显影技术在口腔鳞状细胞癌手术治疗中的应用进展[J]. 国际口腔医学杂志, 2025, 52(3): 405-410.
[10] 郑书豪,李梓瑕,徐欣. Wnt/β-catenin信号通路在味蕾发育和损伤修复中的作用[J]. 国际口腔医学杂志, 2025, 52(3): 411-418.
[11] 卢妍蓓,李正娟,雷蕾,罗晶晶. 磷脂酰肌醇3激酶相关放射抵抗机制在口腔鳞状细胞癌中的研究进展[J]. 国际口腔医学杂志, 2025, 52(2): 246-256.
[12] 李京哲, 张素欣. 磷脂酰肌醇3-激酶/蛋白激酶B通路抑制剂在口腔鳞状细胞癌中的研究进展[J]. 国际口腔医学杂志, 2025, 52(1): 34-41.
[13] 冯玉衡,刘飞,张艳艳,沈颉飞. 泛连接蛋白调控口颌面疼痛作用及机制的研究进展[J]. 国际口腔医学杂志, 2024, 51(6): 756-762.
[14] 李冰芷, 刘云坤, 王文轩, 侯泽宇, 唐金茹, 李龙江. 口腔鳞状细胞癌嗜神经侵袭的研究进展[J]. 国际口腔医学杂志, 2024, 51(3): 362-367.
[15] 王文轩,刘云坤,李冰芷,黄能文,侯泽宇,唐金茹,李龙江. 晚期糖基化终产物在口腔鳞状细胞癌发展及治疗的研究进展[J]. 国际口腔医学杂志, 2024, 51(2): 208-216.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!