سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Nasrpour Navaei, Zahra, Taghehchian, Negin, Zangouei, Amir Sadra, Abbaszadegan, Mohammad reza, Moghbeli, Meysam. (1402). MicroRNA-506 as a tumor suppressor in anaplastic thyroid carcinoma by regulation of WNT and NOTCH signaling pathways. , 26(5), 594-602. doi: 10.22038/ijbms.2023.69174.15069
Zahra Nasrpour Navaei; Negin Taghehchian; Amir Sadra Zangouei; Mohammad reza Abbaszadegan; Meysam Moghbeli. "MicroRNA-506 as a tumor suppressor in anaplastic thyroid carcinoma by regulation of WNT and NOTCH signaling pathways". , 26, 5, 1402, 594-602. doi: 10.22038/ijbms.2023.69174.15069
Nasrpour Navaei, Zahra, Taghehchian, Negin, Zangouei, Amir Sadra, Abbaszadegan, Mohammad reza, Moghbeli, Meysam. (1402). 'MicroRNA-506 as a tumor suppressor in anaplastic thyroid carcinoma by regulation of WNT and NOTCH signaling pathways', , 26(5), pp. 594-602. doi: 10.22038/ijbms.2023.69174.15069
Nasrpour Navaei, Zahra, Taghehchian, Negin, Zangouei, Amir Sadra, Abbaszadegan, Mohammad reza, Moghbeli, Meysam. MicroRNA-506 as a tumor suppressor in anaplastic thyroid carcinoma by regulation of WNT and NOTCH signaling pathways. , 1402; 26(5): 594-602. doi: 10.22038/ijbms.2023.69174.15069

MicroRNA-506 as a tumor suppressor in anaplastic thyroid carcinoma by regulation of WNT and NOTCH signaling pathways

Iranian Journal of Basic Medical Sciences
مقاله 14، دوره 26، شماره 5، مرداد 2023، صفحه 594-602    اصل مقاله (1.71 M)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2023.69174.15069
نویسندگان
Zahra Nasrpour Navaei1؛ Negin Taghehchian2؛ Amir Sadra Zangouei3؛ Mohammad reza Abbaszadegan2؛ Meysam Moghbeli* 1، 2
1Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
چکیده
Objective(s): Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid tumor type that has a poor prognosis due to its high therapeutic resistance. Since ATC accounts for half of thyroid cancer-related deaths, it is required to introduce novel therapeutic targets to increase survival in ATC patients. WNT and NOTCH signaling pathways are the pivotal regulators of cell proliferation and migration that can be regulated by microRNAs. We assessed the role of miR-506 in the regulation of cell migration, apoptosis, and drug resistance via NOTCH and WNT pathways in ATC cells.
Materials and Methods: The levels of miR-506 expressions were assessed in ATC cells and tissues. The levels of NOTCH, WNT, and EMT-related gene expressions were also assessed in miR-506 ectopic expressed cells compared with controls. Cell migration and drug resistance were also evaluated to assess the role of miR-506 in the regulation of ATC aggressiveness. 
Results: There were significant miR-506 down-regulations in ATC cells and clinical samples compared with normal cells and margins. MiR-506 suppressed NOTCH and WNT signaling pathways through LEF1, DVL, FZD1, HEY2, HES5, and HEY2 down-regulations, and APC and GSK3b up-regulations. MiR-506 significantly inhibited ATC cell migration and EMT (P=0.028). Moreover, miR-506 significantly increased Cisplatin (P=0.004), Paclitaxel (P<0.0001), and Doxorubicin (P=0.0014) sensitivities in ATC cells. 
Conclusion: MiR-506 regulated EMT, cell migration, and chemoresistance through regulation of WNT and NOTCH signaling pathways in ATC cells. Therefore, after confirmation with animal studies, it can be introduced as an efficient novel therapeutic factor for ATC tumors. 
کلیدواژه‌ها
Anaplastic thyroid - carcinoma؛ Chemo resistance؛ EMT؛ miR-506؛ NOTCH؛ WNT
مراجع
1. Nguyen QT, Lee EJ, Huang MG, Park YI, Khullar A, Plodkowski RA. Diagnosis and treatment of patients with thyroid cancer. Am Health Drug Benefits 2015; 8:30-40.
2. Fallahi P, Ferrari SM, Galdiero MR, Varricchi G, Elia G, Ragusa F, et al. Molecular targets of tyrosine kinase inhibitors in thyroid cancer. Semin Cancer Biol 2020; 79: 180-196.
3. Ohori NP. Molecular testing and thyroid nodule management in North America. Gland Surg 2020; 9:1628-1638.
4. Ancker OV, Krüger M, Wehland M, Infanger M, Grimm D. Multikinase Inhibitor Treatment in Thyroid Cancer. Int J Mol Sci 2019; 21:10-28.
5. Jayarangaiah A, Sidhu G, Brown J, Barrett-Campbell O, Bahtiyar G, Youssef I, et al. Therapeutic options for advanced thyroid cancer. Int J Clin Endocrinol Metab 2019; 5:26-34.
6. Fagin JA, Wells SA, Jr. Biologic and Clinical Perspectives on Thyroid Cancer. N Engl J Med 2016; 375:1054-1067.
7. Chintakuntlawar AV, Foote RL, Kasperbauer JL, Bible KC. Diagnosis and Management of Anaplastic Thyroid Cancer. Endocrinol Metab Clin North Am 2019; 48:269-284.
8. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119:1420-1428.
9. Pastushenko I, Blanpain C. EMT Transition States during Tumor Progression and Metastasis. Trends Cell Biol 2019; 29:212-226.
10. Wilson C, Nicholes K, Bustos D, Lin E, Song Q, Stephan JP, et al. Overcoming EMT-associated resistance to anti-cancer drugs via Src/FAK pathway inhibition. Oncotarget 2014; 5:7328-7341.
11. Du B, Shim JS. Targeting epithelial-mesenchymal transition (emt) to overcome drug resistance in cancer. Molecules 2016; 21:965-979.
12. Moghbeli M, Mosannen Mozaffari H, Memar B, Forghanifard MM, Gholamin M, Abbaszadegan MR. Role of MAML1 in targeted therapy against the esophageal cancer stem cells. J Transl Med 2019; 17:126.
13. Steinhart Z, Angers S. Wnt signaling in development and tissue homeostasis. Development 2018; 145:dev146589.
14. Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature 2005; 434:843-850.
15. Coelho BP, Fernandes CFL, Boccacino JM, Souza M, Melo-Escobar MI, Alves RN, et al. Multifaceted WNT signaling at the crossroads between epithelial-mesenchymal transition and autophagy in glioblastoma. Front Oncol 2020; 10:597743.
16. Abbaszadegan MR, Moghbeli M. Role of MAML1 and MEIS1 in esophageal squamous cell carcinoma depth of invasion. Pathol Oncol Res 2018; 24:245-250.
17. Qiao L, Wong BC. Role of NOTCH signaling in colorectal cancer. Carcinogenesis 2009; 30:1979-1986.
18. Yuan X, Wu H, Han N, Xu H, Chu Q, Yu S, et al. NOTCH signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application. J Hematol Oncol 2014; 7:1-10.
19. Moghbeli M, Zangouei AS, Nasrpour Navaii Z, Taghehchian N. Molecular mechanisms of the microRNA-132 during tumor progressions. Cancer Cell Int 2021; 21:439.
20. Li M, Marin-Muller C, Bharadwaj U, Chow KH, Yao Q, Chen C. MicroRNAs: control and loss of control in human physiology and disease. World J Surg 2009; 33:667-684.
21. Liu M, Zhang Y, Zhang J, Cai H, Zhang C, Yang Z, et al. MicroRNA-1253 suppresses cell proliferation and invasion of non-small-cell lung carcinoma by targeting WNT5A. Cell Death Dis 2018; 9:189.
22. Moghbeli M. MicroRNAs as the critical regulators of Cisplatin resistance in ovarian cancer cells. J Ovarian Res 2021; 14:127.
23. Song JL, Nigam P, Tektas SS, Selva E. microRNA regulation of Wnt signaling pathways in development and disease. Cell Signal 2015; 27:1380-1391.
24. Wang Z, Li Y, Kong D, Ahmad A, Banerjee S, Sarkar FH. Cross-talk between miRNA and NOTCH signaling pathways in tumor development and progression. Cancer Lett 2010; 292:141-148.
25. Chen Z, Liu S, Tian L, Wu M, Ai F, Tang W, et al. miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1. Oncotarget 2015; 6:38139-38150.
26. Wang Y, Cui M, Sun BD, Liu FB, Zhang XD, Ye LH. MiR-506 suppresses proliferation of hepatoma cells through targeting YAP mRNA 3’UTR. Acta Pharmacol Sin 2014; 35:1207-1214.
27. Streicher KL, Zhu W, Lehmann KP, Georgantas RW, Morehouse CA, Brohawn P, et al. A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth. Oncogene 2012; 31:1558-1570.
28. Tong JL, Zhang CP, Nie F, Xu XT, Zhu MM, Xiao SD, et al. MicroRNA 506 regulates expression of PPAR alpha in hydroxycamptothecin-resistant human colon cancer cells. FEBS Lett 2011; 585:3560-3568.
29. Lima CR, Geraldo MV, Fuziwara CS, Kimura ET, Santos MF. MiRNA-146b-5p upregulates migration and invasion of different Papillary Thyroid Carcinoma cells. BMC Cancer 2016; 16:1-3.
30. Yu F, Lv M, Li D, Cai H, Ma L, Luo Q, et al. MiR-506 Over-Expression Inhibits Proliferation and Metastasis of Breast Cancer Cells. Med Sci Monit 2015; 21:1687-1692.
31. Wen SY, Lin Y, Yu YQ, Cao SJ, Zhang R, Yang XM, et al. miR-506 acts as a tumor suppressor by directly targeting the hedgehog pathway transcription factor Gli3 in human cervical cancer. Oncogene 2015; 34:717-725.
32. Chen L, Wang X, Ji C, Hu J, Fang L. MiR-506-3p suppresses papillary thyroid cancer cells tumorigenesis by targeting YAP1. Pathol Res Pract 2020; 216:153231.
33. Zhu J, Zhang Q, Jin XY, Cai JB, Chen X, Shi WB, et al. MiR-506 suppresses papillary thyroid carcinoma cell proliferation and metastasis via targeting IL17RD. Eur Rev Med Pharmacol Sci 2019; 23:2856-2862.
34. Liu G, Xue F, Zhang W. miR-506: a regulator of chemo-sensitivity through suppression of the RAD51-homologous recombination axis. Chin J Cancer 2015; 34:485-487.
35. Sun Y, Wu J, Dong X, Zhang J, Meng C, Liu G. MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/beta-catenin in serous ovarian cancers. Transl Oncol 2021; 14:100987.
36. Li J, Wu H, Li W, Yin L, Guo S, Xu X, et al. Downregulated miR-506 expression facilitates pancreatic cancer progression and chemoresistance via SPHK1/Akt/NF-kappaB signaling. Oncogene 2016; 35:5501-5514.
37. Zhou H, Lin C, Zhang Y, Zhang X, Zhang C, Zhang P, et al. miR-506 enhances the sensitivity of human colorectal cancer cells to oxaliplatin by suppressing MDR1/P-gp expression. Cell Prolif 2017; 50:e12341.
38. Liu G, Yang D, Rupaimoole R, Pecot CV, Sun Y, Mangala LS, et al. Augmentation of response to chemotherapy by microRNA-506 through regulation of RAD51 in serous ovarian cancers. J Natl Cancer Inst 2015; 107:djv108.
39. Bai J, Lai L, Yeo HC, Goh BC, Tan TM. Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol 2004; 36:247-257.
40. Gong M, Chen C, Zhao H, Sun M, Song M. miR-506 suppresses cervical cancer cell proliferation both in vitro and in vivo. Neoplasma 2018; 65:331-338.
41. Markova SM, Kroetz DL. ABCC4 is regulated by microRNA-124a and microRNA-506. Biochem Pharmacol 2014; 87:515-522.
42. Jiang J, Tang YL, Liang XH. EMT: A new vision of hypoxia promoting cancer progression. Cancer Biol Ther 2011; 11:714-723.
43. Hou Y. MiR-506 inhibits cell proliferation, invasion, migration and epithelial-to-mesenchymal transition through targeting RWDD4 in human bladder cancer. Oncol Lett 2019; 17:73-78.
44. Sakimura S, Sugimachi K, Kurashige J, Ueda M, Hirata H, Nambara S, et al. The miR-506-Induced Epithelial-Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer. Ann Surg Oncol 2015; 22 Suppl 3:S1436-1443.
45. Zhao J, Zeng XB, Zhang HY, Xiang JW, Liu YS. Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p. Open Med (Wars) 2020; 15:921-931.
46. Liu Y, Yan W, Zhou D, Jin G, Cheng X. Long noncoding RNA HOXA11AS accelerates cell proliferation and epithelialmesenchymal transition in hepatocellular carcinoma by modulating the miR5063p/Slug axis. Int J Mol Med 2020; 46:1805-1815.
47. Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, et al. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 2015; 527:525-530.
48. Fu X, Deng X, Xiao W, Huang B, Yi X, Zou Y. Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis. Am J Cancer Res 2021; 11:3841-3856.
49. Wang GJ, Jiao BP, Liu YJ, Li YR, Deng BB. Reactivation of microRNA-506 inhibits gastric carcinoma cell metastasis through ZEB2. Aging (Albany NY) 2019; 11:1821-1831.
50. Wang DP, Tang XZ, Liang QK, Zeng XJ, Yang JB, Xu J. microRNA-599 promotes apoptosis and represses proliferation and epithelial-mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2-depentent NOTCH signaling pathway. J Cell Physiol 2020; 235:2492-2505.
51. Hou Y, Feng F, Yang R. Effect of miR449amediated NOTCH signaling pathway on the proliferation, apoptosis and invasion of papillary thyroid carcinoma cells. Oncol Rep 2020; 43:471-480.
52. Spitschak A, Meier C, Kowtharapu B, Engelmann D, Putzer BM. MiR-182 promotes cancer invasion by linking RET oncogene activated NF-kappaB to loss of the HES1/NOTCH1 regulatory circuit. Mol Cancer 2017; 16:24.
53. Zhao X, Shen F, Yang B. LncRNA LINC01410 Induced by MYC accelerates glioma progression via sponging miR-506-3p and modulating NOTCH2 expression to motivate NOTCH signaling pathway. Cell Mol Neurobiol 2021; 42: 1513-1521.
54. Liu H, Yin Y, Hu Y, Feng Y, Bian Z, Yao S, et al. miR-139-5p sensitizes colorectal cancer cells to 5-fluorouracil by targeting NOTCH-1. Pathol Res Pract 2016; 212:643-649.
55. Abbaszadegan MR, Riahi A, Forghanifard MM, Moghbeli M. WNT and NOTCH signaling pathways as activators for epidermal growth factor receptor in esophageal squamous cell carcinoma. Cell Mol Biol Lett 2018; 23:1-9.
56. Gong X, Li W, Dong L, Qu F. CircUBAP2 promotes SEMA6D expression to enhance the cisplatin resistance in osteosarcoma through sponging miR-506-3p by activating Wnt/beta-catenin signaling pathway. J Mol Histol 2020; 51:329-340.
57. Zhang Y, Lin C, Liao G, Liu S, Ding J, Tang F, et al. MicroRNA-506 suppresses tumor proliferation and metastasis in colon cancer by directly targeting the oncogene EZH2. Oncotarget 2015; 6:32586-32601.
58. Zhu XW, Wang J, Zhu MX, Wang YF, Yang SY, Ke XY. MicroRNA-506 inhibits the proliferation and invasion of mantle cell lymphoma cells by targeting B7H3. Biochem Biophys Res Commun 2019; 508:1067-1073.
59. Wang Y, Lei X, Gao C, Xue Y, Li X, Wang H, et al. MiR-506-3p suppresses the proliferation of ovarian cancer cells by negatively regulating the expression of MTMR6. J Biosci 2019; 44:126.
60. Abbaszadegan MR, Taghehchian N, Li L, Aarabi A, Moghbeli M. Contribution of KCTD12 to esophageal squamous cell carcinoma. BMC Cancer 2018; 18:1-7.

آمار
تعداد مشاهده مقاله: 370
تعداد دریافت فایل اصل مقاله: 413