切换至 "中华医学电子期刊资源库"

中华普通外科学文献(电子版) ›› 2026, Vol. 20 ›› Issue (05) : 346 -351. doi: 10.3877/cma.j.issn.1674-0793.2026.05.010

综述

非编码RNA:甲状腺癌PI3K/AKT通路的新型调节因子与潜在靶点
曹芮宁, 景浩强, 张语涵, 萨日†()   
  1. 130021 吉林,吉林大学第一医院核医学科
  • 收稿日期:2025-11-07 出版日期:2026-10-01
  • 通信作者: 萨日
  • 基金资助:
    国家自然科学基金-青年科学基金项目(82202204)

Noncoding RNA: novel regulators and potential targets of the PI3K/AKT pathway in thyroid cancer

Ruining Cao, Haoqiang Jing, Yuhan Zhang, Ri Sa†()   

  1. Deparatment of Nuclear Medicine, the First Hospital of Jilin University, Jilin 130021, China
  • Received:2025-11-07 Published:2026-10-01
  • Corresponding author: Ri Sa
引用本文:

曹芮宁, 景浩强, 张语涵, 萨日. 非编码RNA:甲状腺癌PI3K/AKT通路的新型调节因子与潜在靶点[J/OL]. 中华普通外科学文献(电子版), 2026, 20(05): 346-351.

Ruining Cao, Haoqiang Jing, Yuhan Zhang, Ri Sa. Noncoding RNA: novel regulators and potential targets of the PI3K/AKT pathway in thyroid cancer[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2026, 20(05): 346-351.

甲状腺癌(TC)是内分泌系统中最常见的恶性肿瘤之一,患病率逐年升高。磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)信号通路介导多种关键细胞信号分子相互作用,并参与调控细胞的多种功能,包括细胞增殖、凋亡、侵袭、转移及上皮-间质转化。此外,在TC 131I治疗反应中,PI3K/AKT通路也扮演着重要角色。研究表明,非编码RNA(ncRNA)包括微RNA(miRNA)、长链非编码RNA(lncRNA)和环状RNA(circRNA),可直接或间接调控PI3K/AKT信号通路;反过来,PI3K/AKT也调节ncRNA的表达。本综述旨在总结ncRNA与PI3K/AKT信号通路之间的相互作用,以及它们在TC生物学行为中的作用,并尝试阐释这些组分之间存在的复杂反馈回路。

Thyroid cancer (TC) is one of the most common endocrine malignancies, showing rapidly increasing incidence. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is a crucial pathway that interacts with various key cell signaling molecules. It is responsible for a wide range of cellular activities in TC, including cell proliferation, apoptosis, invasion, metastasis and epithelial-mesenchymal transition. In addition, the PI3K/AKT pathway also plays a crucial role in the response to TC 131I therapy. Researches have shed light on the significant role of noncoding RNAs (ncRNAs), which include microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), in regulating key signaling pathways, including the PI3K/AKT pathway. Conversely, PI3K/AKT also regulates the expression of ncRNA. Therefore, this review aims to comprehensively discuss the pivotal role of ncRNAs in regulating the PI3K/AKT pathway, as well as their roles in the biological functions of TC. In addition, we also attempt to elucidate the complex feedback loops that exist between these components.

图1 微RNA调控PI3K/AKT通路影响甲状腺癌的生物学行为 磷脂酰肌醇3激酶(PI3K);蛋白激酶B(AKT);转染期间重排(RET); 磷脂酰肌醇3激酶催化亚基δ(PIK3CD);肾素-血管紧张素系统(RAS);磷脂酰肌醇-4, 5-二磷酸(PIP2);脂酰肌醇-3, 4, 5-三磷酸(PIP3);人第10号染色体缺失的磷酸酶及张力蛋白同源物(PTEN);ADP核糖基化因子鸟苷酸交换因子1(ARFGEF1);E3泛素连接酶Pellino-1(PELI1);核不均一核糖核蛋白F(HNRNPF);配对盒基因8(PAX8);生长抑制特异性1(GAS1);蛋白磷酸酶2调控亚基B(PPP2R2A)
图2 长链非编码RNA调控PI3K/AKT通路影响甲状腺癌的生物学行为 磷脂酰肌醇3激酶(PI3K);蛋白激酶B(AKT);间质-上皮转化因子(c-Met/MET);信号转导及转录活化因子3(STAT3);α/β水解酶域11反义RNA1(ABHD11-AS1);白细胞介素增强子结合因子3(ILF3);二肽基肽酶-4(DPP4);生殖器形态发生抑制因子1(SMG1);HOX转录反义RNA(HOTAIR);X染色体失活特异转录因子(XIST);核仁小RNA宿主基因7(SNHG7);核仁小RNA宿主基因3(SNHG3);生长抑制特异性5(GAS5);磷脂酰肌醇-4, 5-二磷酸(PIP2);磷脂酰肌醇-3, 4, 5-三磷酸(PIP3);人第10号染色体缺失的磷酸酶及张力蛋白同源物(PTEN)
图3 环状RNA调控PI3K/AKT通路影响甲状腺癌的生物学行为 磷脂酰肌醇3激酶(PI3K);蛋白激酶B(AKT);酪蛋白激酶ⅡA1(CSNK2A1);高迁移率组蛋白质B1(HMGB1);磷脂酰肌醇-4, 5-二磷酸(PIP2);脂酰肌醇-3, 4, 5-三磷酸(PIP3);人第10号染色体缺失的磷酸酶及张力蛋白同源物(PTEN);间质-上皮转化因子(c-Met/MET)
[1]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209–249.
[2]
Li Z, Lv D, Niu L, et al. The role of WNT signaling in papillary thyroid cancer: mechanisms, epigenetic regulation, therapeutic resistance, and emerging clinical strategies[J]. Pathol Res Pract, 2025, 275: 156231.
[3]
He Y, Sun MM, Zhang GG, et al. Targeting PI3K/Akt signal transduction for cancer therapy[J]. Sig Transduct Target Ther, 2021, 6(1): 425.
[4]
Voinea IA, Petrova E, Dumitru N, et al. Pathogenesis and management strategies in radioiodine-refractory differentiated thyroid cancer: from molecular mechanisms toward therapeutic approaches: A comprehensive review[J]. J Clin Med, 2024, 13(23): 7161.
[5]
Drilon A, Hu ZI, Lai GGY, et al. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes[J]. Nat Rev Clin Oncol, 2018, 15(3): 151–167.
[6]
Lan Y, Liu D, Liang B, et al. ITGA3-MET interaction promotes papillary thyroid cancer progression via ERK and PI3K/AKT pathways[J]. Ann Med, 2025, 57(1): 2483379.
[7]
Yehia L, Keel E, Eng C. The clinical spectrum of PTEN mutations[J]. Annu Rev Med, 2020, 71: 103–116.
[8]
Salim U, Kumar A, Kulshreshtha R, et al. Biogenesis, characterization, and functions of mirtrons[J]. Wires RNA, 2022, 13(1): e1680.
[9]
Han J, Zhang M, Nie C, et al. MiR-215 suppresses papillary thyroid cancer proliferation, migration, and invasion through the AKT/GSK-3β/Snail signaling by targeting ARFGEF1[J]. Cell Death Dis, 2019, 10(3): 195.
[10]
Bu Q, You F, Pan G, et al. MiR-125b inhibits anaplastic thyroid cancer cell migration and invasion by targeting PIK3CD[J]. Biomed Pharmacother, 2017, 88: 443–448.
[11]
Boufraqech M, Zhang L, Jain M, et al. MiR-145 suppresses thyroid cancer growth and metastasis and targets AKT3[J]. Endocr Relat Cancer, 2014, 21(4): 517–531.
[12]
Tan J, Li C, Ren L, et al. miR-451a suppresses papillary thyroid cancer cell proliferation and invasion and facilitates apoptosis through targeting DCBLD2 and AKT1[J]. Mol Cell Probes, 2022, 66: 101863.
[13]
Li J, Zhang Z, Hu J, et al. miR-1246 regulates the PI3K/AKT signaling pathway by targeting PIK3AP1 and inhibits thyroid cancer cell proliferation and tumor growth[J]. Mol Cell Biochem, 2022, 477(3): 649–661.
[14]
Ramírez-Moya J, Wert-Lamas L, Santisteban P. microRNA-146b promotes PI3K/AKT pathway hyperactivation and thyroid cancer progression by targeting PTEN[J]. Oncogene, 2018, 37(25): 3369–3383.
[15]
Huang Y, Yu S, Cao S, et al. MicroRNA-222 promotes invasion and metastasis of papillary thyroid cancer through targeting protein phosphatase 2 regulatory subunit B alpha expression[J]. Thyroid, 2018, 28(9): 1162–1173.
[16]
Montero-Conde C, Graña-Castro O, Martín-Serrano G, et al. Hsa-miR-139–5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing[J]. Int J Cancer, 2020, 146(2): 521–530.
[17]
Zheng T, Zhou Y, Xu X, et al. MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma[J]. J Transl Med, 2022, 20(1): 20.
[18]
Tang Y, Wang J, Lian Y, et al. Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer[J]. Mol Cancer, 2017, 16(1): 42.
[19]
Feng J, Zhou Q, Yi H, et al. A novel lncRNA n384546 promotes thyroid papillary cancer progression and metastasis by acting as a competing endogenous RNA of miR-145–5p to regulate AKT3[J]. Cell Death Dis, 2019, 10(6): 433.
[20]
Du X, Hao Y, Liu M, et al. LncRNA HOTAIR promotes cell proliferation and migration in papillary thyroid carcinoma cells by sponging miR-206/c-Met axis[J]. J Mol Histol, 2025, 56(5): 283.
[21]
Wen J, Wang H, Dong T, et al. STAT3-induced upregulation of lncRNA ABHD11-AS1 promotes tumour progression in papillary thyroid carcinoma by regulating miR-1301–3p/STAT3 axis and PI3K/AKT signalling pathway[J]. Cell Prolif, 2019, 52(2): e12569.
[22]
Du P, Liu F, Liu Y, et al. Linc00210 enhances the malignancy of thyroid cancer cells by modulating miR-195–5p/IGF1R/Akt axis[J]. J Cell Physiol, 2020, 235(2): 1001–1012.
[23]
Zhang L, Zhang J, Li S, et al. Genomic amplification of long noncoding RNA HOTAIRM1 drives anaplastic thyroid cancer progression via repressing miR-144 biogenesis[J]. RNA Biol, 2021, 18(4): 547–562.
[24]
Hejazi M, Jafari T, Yari A, et al. A novel long non-coding RNA, PICSAR, promotes thyroid cancer progression through the hsa-miR-320A/hsa-miR-485/RAPGEFL1 axis[J]. Med Oncol, 2025, 42(10): 448.
[25]
Chen W, Yu J, Xie R, et al. Roles of the SNHG7/microRNA-9–5p/DPP4 CeRNA network in the growth and 131I resistance of thyroid carcinoma cells through PI3K/Akt activation[J]. Oncol Rep, 2021, 45(4): 3.
[26]
Li L, Lin X, Xu P, et al. LncRNA GAS5 sponges miR-362–5p to promote sensitivity of thyroid cancer cells to 131I by upregulating SMG1[J]. IUBMB Life, 2020, 72(11): 2420–2431.
[27]
Liu H, Deng H, Zhao Y, et al. LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling[J]. J Exp Clin Cancer Res, 2018, 37(1): 279.
[28]
Duan Y, Wang Z, Xu L, et al. LncRNA SNHG3 acts as a novel tumor suppressor and regulates tumor proliferation and metastasis via AKT/mTOR/ERK pathway in papillary thyroid carcinoma[J]. J Cancer, 2020, 11(12): 3492–3501.
[29]
Li Z, Gao Y, Li L, et al. Curcumin inhibits papillary thyroid cancer cell proliferation by regulating lncRNA LINC00691[J]. Anal Cell Pathol, 2022, 2022: 5946670.
[30]
Wang Y, Dzakah EE, Wang X. Molecular basis of backsplicing regulation and its application to manipulate circRNA levels[J]. RNA Biol, 2025, 22(1): 1–10.
[31]
Han P, Chen G, Zhang Q, et al. Circ_PSD3 stimulates cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in papillary thyroid carcinoma via the regulation of miR-145–5p/miR-338–3p/HMGB3 axis[J]. J Biochem Mol Toxicol, 2025, 39(8): e70402.
[32]
Dong LP, Chen LY, Bai B, et al. Circ_0067934 promotes the progression of papillary thyroid carcinoma cells through miR-1301–3p/HMGB1 axis[J]. Neoplasma, 2022, 69(1): 1–15.
[33]
Zheng H, Fu Q, Ma K, et al. Circ_0079558 promotes papillary thyroid cancer progression by binding to miR-26b-5p to activate MET/AKT signaling[J]. Endocr J, 2021, 68(11): 1247–1266.
[34]
Chen L, Zhuo D, Yuan H. Circ_100395 impedes malignancy and glycolysis in papillary thyroid cancer: involvement of PI3K/AKT/mTOR signaling pathway[J]. Immunol Lett, 2022, 246: 10–17.
[35]
Shu C, Wang S, Hu J, et al. CircNDST1 promotes papillary thyroid cancer progression via its interaction with CSNK2A1 to activate the PI3K-Akt pathway and epithelial–mesenchymal transition[J]. J Endocrinol Investig, 2023, 46(3): 545–557.
[36]
Zhou T, Li Z, Huang W, et al. Genome-wide analyses identify circAQR, a circular RNA suppressing proliferation but promoting migration and invasion in thyroid cancer[J]. NPJ Precis Oncol, 2025, 9(1): 171.
[1] 凌洁, 吴世婷, 尹勇, 邓显光, 周瑶, 龚婕, 赵丹, 刘丽芳. 血清标志物在肿块期肉芽肿性小叶性乳腺炎、乳腺癌及乳腺纤维腺瘤中的诊断价值[J/OL]. 中华乳腺病杂志(电子版), 2026, 20(04): 236-244.
[2] 黄嘉楠, 杨均政, 张华, 陈柏豪, 陈楚仪, 何琪, 陈鹏. 环状RNA调控激素性股骨头坏死的机制与研究进展[J/OL]. 中华关节外科杂志(电子版), 2025, 19(06): 755-760.
[3] 陈伟, 方杰. 子宫内膜息肉患者外周血环状RNA ATRNL1与卵泡抑素表达水平及其对宫腔镜下电切术后复发的预测价值[J/OL]. 中华妇幼临床医学杂志(电子版), 2026, 22(02): 140-147.
[4] 刘可文, 向鹏程, 韩俊毅. miR-129通过靶向阳离子氨基酸转运蛋白1抑制结肠癌细胞的精氨酸代谢[J/OL]. 中华普通外科学文献(电子版), 2026, 20(04): 225-229.
[5] 罗文勇, 黄文龙, 阮沁桐, 蔡莹, 王欣, 吴柱国, 王利玲, 于海兵. 甲状腺癌术后并发低钙血症的发病风险预测模型构建[J/OL]. 中华普通外科学文献(电子版), 2026, 20(04): 257-264.
[6] 柳敏, 赵敬柱, 候秀坤, 张淼, 吴小灿, 郑向前. SF3B5在甲状腺乳头状癌中的表达特征与临床意义及其抑制肿瘤进展的分子机制研究[J/OL]. 中华普通外科学文献(电子版), 2026, 20(02): 103-111.
[7] 杨婷麟, 黄韬. 人工智能应用于甲状腺结节评估的进展与挑战[J/OL]. 中华普通外科学文献(电子版), 2026, 20(01): 60-65.
[8] 张宇, 夏晓天, 郭明高, 樊友本. 两种术式治疗甲状腺微小乳头状癌的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(05): 480-484.
[9] 韩昭, 张克俭, 聂阿娜, 赵建红, 李晓武, 陈晓丽, 胡玮, 张伟, 李杨, 杨雪. 3D腔镜甲状腺术中精细解剖喉返神经喉外多分支一例报道[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(03): 305-306.
[10] 常清语, 冯骋骋, 刘学敏, 姜一鵾, 王海强, 姚昶. 免充气锁骨下入路腔镜甲状腺癌根治术在甲状腺乳头状癌中的应用[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(02): 195-198.
[11] 孙光泽, 姚永强, 解继平, 万毅, 杨诗语, 张岷, 葛雨川, 张楚宁. 喉返神经隧道解剖法在经口腔前庭及颏下入路腔镜甲状腺手术中应用[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(02): 203-204.
[12] 刘楷, 代文杰. 甲状腺癌颈部淋巴结清扫术后乳糜漏的预防与治疗措施[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(01): 87-90.
[13] 张宇坤, 王春林, 周珉玮, 李震洋, 周易明, 顾晓冬, 项建斌. 放疗诱导微卫星稳定型结直肠癌细胞外泌体成分变化及其增强CD8+T细胞功能的体外研究[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(06): 526-532.
[14] 伍宵, 唐颖, 张曦文, 邱海波. 表观遗传修饰调控急性呼吸窘迫综合征发病机制的研究进展[J/OL]. 中华重症医学电子杂志, 2026, 12(02): 202-207.
[15] 《非编码RNA在肾细胞癌液体活检中的应用专家共识》编写组. 非编码RNA在肾细胞癌液体活检中的应用专家共识[J/OL]. 中华老年病研究电子杂志, 2026, 13(02): 10-18.
阅读次数
全文


摘要


AI
小
编
AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?