Research progress of phosphatidylinositol-3-kinase/protein kinase B signaling pathway in thyroid cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Lei ¹ , CUI Siqian ¹ , ZHANG Huiqiang ¹ , ZHANG Jin ² ,  LIU Jing ²

1. The First Clinical College of Shanxi Medical University, Taiyuan 030001, P. R. China;
2. Department of Thyroid Surgery, The First Hospital of Shanxi Medical University, Taiyuan 030001, P. R. China;

Corresponding author：

LIU Jing, Email: liujing5585@163.com

Keywords：

phosphatidylinositol-3-kinase/protein kinase B signaling pathway; thyroid cancer; review

DOI：

10.7507/1007-9424.202205076

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To understand the research status of phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the thyroid cancer (TC), as well as its role in the occurrence, cell differentiation, invasion, and metastasis of the TC, so as to find potential targets for treatment of TC. Method The literature about the research of PI3K/AKT signaling pathway in the TC was searched and summarized. Results The PI3K/AKT signaling pathway was abnormally activated directly or indirectly in the TC, resulting in inhibition of cell apoptosis, malignant proliferation, accelerated cycle progression, invasion, and metastasis, etc., which promoted the occurrence and development of the TC. There were also some tumor suppressor genes, microRNAs, long chain non-coding RNAs, etc., which indirectly inhibited the activation of PI3K/AKT signaling pathway, or directly acted on it inhibiting its activity to inhibit the occurrence and development of the TC. Conclusions For the TC, some proteins, genes, microRNAs, and long chain non-coding RNAs directly or indirectly activate the PI3K/AKT signaling pathway through different targets to promote the occurrence and development of TC. At the same time, many targets inhibit the activation of the PI3K/AKT signaling pathway, which inhibits the malignant proliferation, invasion, and metastasis of TC. At present, there have been studies trying to use PI3K/AKT signaling pathway as a breakthrough for the treatment of TC. In-depth exploration of the role of PI3K/AKT signaling pathway in different TC is of great significance to find new targets for the treatment of TC.

Citation： LI Lei, CUI Siqian, ZHANG Huiqiang, ZHANG Jin, LIU Jing. Research progress of phosphatidylinositol-3-kinase/protein kinase B signaling pathway in thyroid cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(1): 91-98. doi: 10.7507/1007-9424.202205076 Copy

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24.	No authors listed. Retraction notice for: “lncRNA CCAT1 promotes cell proliferation, migration, and invasion by down-regulation of miR-143 in FTC-133 thyroid carcinoma cell line” [Braz J Med Biol Res (2018) 51(6): e7046]. Braz J Med Biol Res, 2021, 54(6): e7046retraction. doi: 10.1590/1414-431X2020e7046retraction.
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26.	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 Cell Physiol, 2020, 235(2): 1001-1012.
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35.	Gao YT, Zhou YC. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) promotes breast cancer progression by sponging miRNA-381. Eur Rev Med Pharmacol Sci, 2019, 23(15): 6588-6595.
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37.	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. Oncol Rep, 2021, 45(4): 3. doi: 10.3892/or.2021.7954.
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1. Miranda-Filho A, Lortet-Tieulent J, Bray F, et al. Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet Diabetes Endocrinol, 2021, 9(4): 225-234.
2. Vaccarella S, Lortet-Tieulent J, Colombet M, et al. Global patterns and trends in incidence and mortality of thyroid cancer in children and adolescents: a population-based study. Lancet Diabetes Endocrinol, 2021, 9(3): 144-152.
3. Laha D, Nilubol N, Boufraqech M. New therapies for advanced thyroid cancer. Front Endocrinol (Lausanne), 2020, 11: 82. doi: 10.3389/fendo.2020.00082.
4. Aoki M, Fujishita T. Oncogenic roles of the PI3K/AKT/mTOR axis. Curr Top Microbiol Immunol, 2017, 407: 153-189.
5. Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, et al. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol, 2010, 11(5): 329-341.
6. Vasudevan KM, Garraway LA. AKT signaling in physiology and disease. Curr Top Microbiol Immunol, 2010, 347: 105-133.
7. Álvarez-Garcia V, Tawil Y, Wise HM, et al. Mechanisms of PTEN loss in cancer: it’s all about diversity. Semin Cancer Biol, 2019, 59: 66-79.
8. Bunney TD, Katan M. Phosphoinositide signalling in cancer: beyond PI3K and PTEN. Nat Rev Cancer, 2010, 10(5): 342-352.
9. Wei X, Luo L, Chen J. Roles of mTOR signaling in tissue regeneration. Cells, 2019, 8(9): 1075. doi: 10.3390/cells8091075.
10. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell, 2012, 149(2): 274-293.
11. Bhat M, Robichaud N, Hulea L, et al. Targeting the translation machinery in cancer. Nat Rev Drug Discov, 2015, 14(4): 261-278.
12. Xing YQ, Li A, Yang Y, et al. The regulation of FOXO1 and its role in disease progression. Life Sci, 2018, 193: 124-131.
13. Ma Z, Xin Z, Hu W, et al. Forkhead box O proteins: crucial regulators of cancer EMT. Semin Cancer Biol, 2018, 50: 21-31.
14. Chen C, Luo Y, Su Y, et al. The vitamin D receptor (VDR) protects pancreatic beta cells against Forkhead box class O1 (FOXO1)-induced mitochondrial dysfunction and cell apoptosis. Biomed Pharmacother, 2019, 117: 109170. doi: 10.1016/j.biopha.2019.109170.
15. Wang J, Shen L, Hong H, et al. Atrasentan alleviates high glucose-induced podocyte injury by the microRNA-21/forkhead box O1 axis. Eur J Pharmacol, 2019, 852: 142-150.
16. Lu H, Chen S, You Z, et al. PFKFB4 negatively regulated the expression of histone acetyltransferase GCN5 to mediate the tumorigenesis of thyroid cancer. Dev Growth Differ, 2020, 62(2): 129-138.
17. Zhao WJ, Zhu LL, Yang WQ, et al. LPAR5 promotes thyroid carcinoma cell proliferation and migration by activating class ⅠA PI3K catalytic subunit p110β. Cancer Sci, 2021, 112(4): 1624-1632.
18. Li D, Yang Y, Chen B, et al. MOF regulates TNK2 transcription expression to promote cell proliferation in thyroid cancer. Front Pharmacol, 2020, 11: 607605. doi: 10.3389/fphar.2020.607605.
19. Su X, Chen D, Zhu L, et al. SGSM2 inhibits thyroid cancer progression by activating RAP1 and enhancing competitive RAS inhibition. Cell Death Dis, 2022, 13(3): 218. doi: 10.1038/s41419-022-04598-y.
20. Chang F, Xing P, Song F, et al. The role of T-box genes in the tumorigenesis and progression of cancer. Oncol Lett, 2016, 12(6): 4305-4311.
21. Wang N, Li Y, Wei J, et al. TBX1 functions as a tumor suppressor in thyroid cancer through inhibiting the activities of the PI3K/AKT and MAPK/ERK pathways. Thyroid, 2019, 29(3): 378-394.
22. Xia W, Jie W. ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway. Cancer Cell Int, 2020, 20: 94. doi: 10.1186/s12935-020-1098-1.
23. Yang T, Zhai H, Yan R, et al. lncRNA CCAT1 promotes cell proliferation, migration, and invasion by down-regulation of miR-143 in FTC-133 thyroid carcinoma cell line. Braz J Med Biol Res, 2018, 51(6): e7046. doi: 10.1590/1414-431x20187046.
24. No authors listed. Retraction notice for: “lncRNA CCAT1 promotes cell proliferation, migration, and invasion by down-regulation of miR-143 in FTC-133 thyroid carcinoma cell line” [Braz J Med Biol Res (2018) 51(6): e7046]. Braz J Med Biol Res, 2021, 54(6): e7046retraction. doi: 10.1590/1414-431X2020e7046retraction.
25. 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. Mol Cell Biochem, 2022, 477(3): 649-661.
26. 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 Cell Physiol, 2020, 235(2): 1001-1012.
27. Min X, Liu K, Zhu H, et al. Long noncoding RNA LINC003121 inhibits proliferation and invasion of thyroid cancer cells by suppression of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. Med Sci Monit, 2018, 24: 4592-4601.
28. 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 Exp Clin Cancer Res, 2018, 37(1): 279. doi: 10.1186/s13046-018-0950-9.
29. Chen L, Zhuo D, Yuan H. Circ_100395 impedes malignancy and glycolysis in papillary thyroid cancer: involvement of PI3K/AKT/mTOR signaling pathway. Immunol Lett, 2022, 246: 10-17.
30. Li Z, Huang X, Liu A, et al. Circ_PSD3 promotes the progression of papillary thyroid carcinoma via the miR-637/HEMGN axis. Life Sci, 2021, 264: 118622. doi: 10.1016/j.lfs.2020.118622.
31. Zhao J, Li Z, Chen Y, et al. MicroRNA-766 inhibits papillary thyroid cancer progression by directly targeting insulin receptor substrate 2 and regulating the PI3K/Akt pathway. Int J Oncol, 2019, 54(1): 315-325.
32. 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 Transl Med, 2022, 20(1): 20. doi: 10.1186/s12967-021-03226-1.
33. Han M, Chen L, Wang Y. miR-218 overexpression suppresses tumorigenesis of papillary thyroid cancer via inactivation of PTEN/PI3K/AKT pathway by targeting Runx2. Onco Targets Ther, 2018, 11: 6305-6316.
34. Arioka M, Takahashi-Yanaga F. Glycogen synthase kinase-3 inhibitor as a multi-targeting anti-rheumatoid drug. Biochem Pharmacol, 2019, 165: 207-213.
35. Gao YT, Zhou YC. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) promotes breast cancer progression by sponging miRNA-381. Eur Rev Med Pharmacol Sci, 2019, 23(15): 6588-6595.
36. Yao X, Liu C, Liu C, et al. lncRNA SNHG7 sponges miR-425 to promote proliferation, migration, and invasion of hepatic carcinoma cells via Wnt/β-catenin/EMT signalling pathway. Cell Biochem Funct, 2019, 37(7): 525-533.
37. 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. Oncol Rep, 2021, 45(4): 3. doi: 10.3892/or.2021.7954.
38. 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. Cell Prolif, 2019, 52(2): e12569. doi: 10.1111/cpr.12569.
39. Zhang J, Du Y, Zhang X, et al. Downregulation of BANCR promotes aggressiveness in papillary thyroid cancer via the MAPK and PI3K pathways. J Cancer, 2018, 9(7): 1318-1328.
40. Zhao M, Yang F, Sang C, et al. BGL3 inhibits papillary thyroid carcinoma progression via regulating PTEN stability. J Endocrinol Invest, 2021, 44(10): 2165-2174.
41. Pratakpiriya W, Seki F, Otsuki N, et al. Nectin4 is an epithelial cell receptor for canine distemper virus and involved in neurovirulence. J Virol, 2012, 86(18): 10207-10210.
42. Hao RT, Zheng C, Wu CY, et al. NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT. Cancer Manag Res, 2019, 11: 2565-2578.
43. Kang JH, Park JH, Kong JS, et al. PINX1 promotes malignant transformation of thyroid cancer through the activation of the AKT/MAPK/β-catenin signaling pathway. Am J Cancer Res, 2021, 11(11): 5485-5495.
44. Dong X, Akuetteh PDP, Song J, et al. Major Vault protein (MVP) associated with BRAF^V600E mutation is an immune microenvironment-related biomarker promoting the progression of papillary thyroid cancer via MAPK/ERK and PI3K/AKT pathways. Front Cell Dev Biol, 2022, 9: 688370. doi: 10.3389/fcell.2021.688370.
45. Yang J, Ying Y, Zeng X, et al. Transcription factor E2F1 exacerbates papillary thyroid carcinoma cell growth and invasion via upregulation of LINC00152. Anal Cell Pathol (Amst), 2022, 2022: 7081611. doi: 10.1155/2022/7081611.
46. Wang Y, Wang C, Fu Z, et al. miR-30b-5p inhibits proliferation, invasion, and migration of papillary thyroid cancer by targeting GALNT7 via the EGFR/PI3K/AKT pathway. Cancer Cell Int, 2021, 21(1): 618. doi: 10.1186/s12935-021-02323-x.
47. Wang K, Chai L, Qiu Z, et al. Overexpression of TRIM26 suppresses the proliferation, metastasis, and glycolysis in papillary thyroid carcinoma cells. J Cell Physiol, 2019, 234(10): 19019-19027.
48. Maxwell PH, Wiesener MS, Chang GW, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature, 1999, 399(6733): 271-275.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress of phosphatidylinositol-3-kinase/protein kinase B signaling pathway in thyroid cancer

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