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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

miRNA-363-3p Hinders Proliferation, Migration, Invasion and Autophagy of Thyroid Cancer Cells by Controlling SYT1 Transcription to affect NF-κB

Author(s): Jizong Zhang, Guanghui Ren, Tao Huang, Yiming Sang, Yan Zhong* and Yongxiang Yi*

Volume 24, Issue 1, 2024

Published on: 03 July, 2023

Page: [153 - 162] Pages: 10

DOI: 10.2174/1871530323666230504112553

Price: $65

Abstract

Background: Thyroid cancer (TC) is a frequent endocrine malignant tumor with various pathologic types. miRNA-363-3p plays a pivotal part in the occurrence, development, prognosis, and treatment of cancer.

Objective: To explore the mechanism of miRNA-363-3p in TC and provide a new idea for targeted therapy of TC.

Methods: Differential miRNAs and downstream target mRNAs in TC tissues were predicted with bioinformatics analysis. Expression levels of miRNA-363-3p and Synaptotagmin I (SYT1) in TC cells were ascertained by qRT-PCR. Cell migration, invasion, and proliferation were detected by wound healing assay, transwell assay, colony formation assay, CCK-8, and BrdU fluorescence experiment, respectively. Flow cytometry was utilized to detect the levels of apoptosis and necrosis. Immunofluorescence assay was used for detecting autophagosome formation in cells, and the expression levels of autophagy-related proteins, as well as NF-κB related proteins, were measured by western blot. Dual-luciferase reporter gene assay was applied for detecting the interaction between miRNA-363-3p and SYT1.

Results: miRNA-363-3p was prominently down-regulated in TC cells. miRNA-363-3p overexpression suppressed migration, invasion, and proliferation, promoting apoptosis and necrosis of TC cells. As the downstream target of miRNA-363-3p, SYT1 was up-regulated in TC cells. SYT1 overexpression reversed the inhibition of TC cell proliferation, invasion, migration, and autophagy mediated by miRNA-363-3p overexpression. In addition, miRNA-363-3p overexpression inhibited the activation of the NF-κB pathway in cells, while further overexpression of SYT1 weakened the inhibition of miRNA-363-3p overexpression on the NF-κB pathway.

Conclusion: miRNA-363-3p affected the NF-κB signaling pathway by down-regulating SYT1 expression to inhibit the malignant progression of TC cells, providing theoretical support for the treatment of TC.

Keywords: Thyroid cancer, miRNA-363-3p, SYT1; malignant progression, cancer cells, NF-κB pathway.

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[1]
Seib, C.D.; Sosa, J.A. Evolving understanding of the epidemiology of thyroid cancer. Endocrinol. Metab. Clin. North Am., 2019, 48(1), 23-35.
[http://dx.doi.org/10.1016/j.ecl.2018.10.002] [PMID: 30717905]
[2]
Yan, D.G.; Liu, N.; Chao, M.; Tu, Y.Y.; Liu, W.S. SP1-induced upregulation of long noncoding RNA LINC00313 contributes to papillary thyroid cancer progression via the miR-422a. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(3), 1134-1144.
[PMID: 30779082]
[3]
Prete, A.; Borges de Souza, P.; Censi, S.; Muzza, M.; Nucci, N.; Sponziello, M. Update on fundamental mechanisms of thyroid cancer. Front. Endocrinol. (Lausanne), 2020, 11, 102.
[http://dx.doi.org/10.3389/fendo.2020.00102] [PMID: 32231639]
[4]
Ren, Z.F.; Du, M.F.; Fu, H.; Liu, J.; Xia, F.Y.; Du, H.N.; Liu, N. MiR-200c promotes proliferation of papillary thyroid cancer cells via Wnt/β-catenin signaling pathway. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(10), 5512-5518.
[PMID: 32495886]
[5]
Chen, X.; Li, M.; Zhou, H.; Zhang, L. miR-132 targets FOXA1 and exerts tumor-suppressing functions in thyroid cancer. Oncol. Res., 2019, 27(4), 431-437.
[http://dx.doi.org/10.3727/096504018X15201058168730] [PMID: 29523221]
[6]
Lang, B.H.H.; Wong, K.P.; Wan, K.Y.; Lo, C.Y. Significance of metastatic lymph node ratio on stimulated thyroglobulin levels in papillary thyroid carcinoma after prophylactic unilateral central neck dissection. Ann. Surg. Oncol., 2012, 19(4), 1257-1263.
[http://dx.doi.org/10.1245/s10434-011-2105-5] [PMID: 21989667]
[7]
Wang, P.; Gu, J.; Wang, K.; Shang, J.; Wang, W. miR-206 inhibits thyroid cancer proliferation and invasion by targeting RAP1B. J. Cell. Biochem., 2019, 120(11), 18927-18936.
[http://dx.doi.org/10.1002/jcb.29213] [PMID: 31245877]
[8]
Shi, Y.P.; Liu, G.L.; Li, S.; Liu, X.L. miR-17-5p knockdown inhibits proliferation, autophagy and promotes apoptosis in thyroid cancer via targeting PTEN. Neoplasma, 2020, 67(2), 249-258.
[http://dx.doi.org/10.4149/neo_2019_190110N29] [PMID: 31973533]
[9]
Zheng, X.; Rui, S.; Wang, X.F.; Zou, X.H.; Gong, Y.P.; Li, Z.H. circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling. J. Exp. Clin. Cancer Res., 2021, 40(1), 157.
[http://dx.doi.org/10.1186/s13046-021-01964-0] [PMID: 33962657]
[10]
Fan, Y.; Fan, X.; Yan, H.; Liu, Z.; Wang, X.; Yuan, Q.; Xie, J.; Lu, X.; Yang, Y. Hypermethylation of microRNA-497-3p contributes to progression of thyroid cancer through activation of PAK1/β-catenin. Cell Biol. Toxicol., 2022, 1-6.
[http://dx.doi.org/10.1007/s10565-021-09682-1] [PMID: 35066776]
[11]
Geng, X.; Sun, Y.; Fu, J.; Cao, L.; Li, Y. MicroRNA-17-5p inhibits thyroid cancer progression by suppressing Early growth response 2 (EGR2). Bioengineered, 2021, 12(1), 2713-2722.
[http://dx.doi.org/10.1080/21655979.2021.1935137] [PMID: 34130587]
[12]
Fan, B.; Su, B.; Song, G.; Liu, X.; Yan, Z.; Wang, S.; Hu, F.; Yang, J. miR‐363‐3p induces EMT via the Wnt/β‐catenin pathway in glioma cells by targeting CELF2. J. Cell. Mol. Med., 2021, 25(22), 10418-10429.
[http://dx.doi.org/10.1111/jcmm.16970] [PMID: 34636136]
[13]
Mohamed, Z.; Hassan, M.K.; Okasha, S.; Mitamura, T.; Keshk, S.; Konno, Y.; Kato, T.; EL-Khamisy, S.F.; Ohba, Y.; Watari, H. miR-363 confers taxane resistance in ovarian cancer by targeting the Hippo pathway member, LATS2. Oncotarget, 2018, 9(53), 30053-30065.
[http://dx.doi.org/10.18632/oncotarget.25698] [PMID: 30046387]
[14]
Dong, J.; Geng, J.; Tan, W. MiR-363-3p suppresses tumor growth and metastasis of colorectal cancer via targeting SphK2. Biomed. Pharmacother., 2018, 105, 922-931.
[http://dx.doi.org/10.1016/j.biopha.2018.06.052] [PMID: 30021386]
[15]
Chang, J.; Gao, F.; Chu, H.; Lou, L.; Wang, H.; Chen, Y. miR‐363‐3p inhibits migration, invasion, and epithelial–mesenchymal transition by targeting NEDD9 and SOX4 in non‐small‐cell lung cancer. J. Cell. Physiol., 2020, 235(2), 1808-1820.
[http://dx.doi.org/10.1002/jcp.29099] [PMID: 31332786]
[16]
Wang, K.; Yan, L.; Lu, F. miR-363-3p inhibits osteosarcoma cell proliferation and invasion via targeting SOX4. Oncol. Res., 2019, 27(2), 157-163.
[http://dx.doi.org/10.3727/096504018X15190861873459] [PMID: 29471893]
[17]
Liu, J.; Li, Q.; Li, R.; Ren, P.; Dong, S. MicroRNA-363-3p inhibits papillary thyroid carcinoma progression by targeting PIK3CA. Am. J. Cancer Res., 2017, 7(1), 148-158.
[PMID: 28123856]
[18]
Pan, Y.; Zhu, X.; Wang, K.; Chen, Y. MicroRNA-363-3p suppresses anoikis resistance in human papillary thyroid carcinoma via targeting integrin alpha 6. Acta Biochim. Biophys. Sin. (Shanghai), 2019, 51(8), 807-813.
[http://dx.doi.org/10.1093/abbs/gmz066] [PMID: 31257410]
[19]
Meng, S.; Kang, K.; Fei, D.; Yang, S.; Pan, S.; Yu, K. MiR-363-3p/S1PR1 axis inhibits sepsis-induced acute lung injury via the inactivation of NF-kappaB signaling. Exp. Anim., 2022, 71(3), 305-315.
[http://dx.doi.org/10.1538/expanim.21-0160]
[20]
Le, Y.; Wang, Y.; Zhou, L.; Xiong, J.; Tian, J.; Yang, X.; Gai, X.; Sun, Y. Cigarette smoke-induced HMGB1 translocation and release contribute to migration and NF‐κB activation through inducing autophagy in lung macrophages. J. Cell. Mol. Med., 2020, 24(2), 1319-1331.
[http://dx.doi.org/10.1111/jcmm.14789] [PMID: 31769590]
[21]
Lu, H.; Hao, L.; Yang, H.; Chen, J.; Liu, J. miRNA-34a suppresses colon carcinoma proliferation and induces cell apoptosis by targeting SYT1. Int. J. Clin. Exp. Pathol., 2019, 12(8), 2887-2897.
[PMID: 31934125]
[22]
Han, J.; Zhang, M.; Nie, C.; Jia, J.; Wang, F.; Yu, J.; Bi, W.; Liu, B.; Sheng, R.; He, G.; Kong, L.; Zheng, L.; Pang, R.; Ding, Z.; Chen, L.; Guan, Q.; Pan, S.; Meng, X.; Xu, J.; Liu, L.; Zhang, J. miR-215 suppresses papillary thyroid cancer proliferation, migration, and invasion through the AKT/GSK-3β/Snail signaling by targeting ARFGEF1. Cell Death Dis., 2019, 10(3), 195.
[http://dx.doi.org/10.1038/s41419-019-1444-1] [PMID: 30814512]
[23]
Jiang, C.; Cao, Y.; Lei, T.; Wang, Y.; Fu, J.; Wang, Z.; Lv, Z. microRNA-363-3p inhibits cell growth and invasion of non small cell lung cancer by targeting HMGA2. Mol. Med. Rep., 2018, 17(2), 2712-2718.
[PMID: 29207105]
[24]
Hu, F.; Min, J.; Cao, X.; Liu, L.; Ge, Z.; Hu, J.; Li, X. MiR-363-3p inhibits the epithelial-to-mesenchymal transition and suppresses metastasis in colorectal cancer by targeting Sox4. Biochem. Biophys. Res. Commun., 2016, 474(1), 35-42.
[http://dx.doi.org/10.1016/j.bbrc.2016.04.055] [PMID: 27084453]
[25]
Wang, J.; Liang, H.; Ge, H.; Guo, X.; Gu, D.; Yuan, Y. MicroRNA-363-3p inhibits hepatocarcinogenesis by targeting HMGA2 and is associated with liver cancer stage. Mol. Med. Rep., 2019, 19(2), 935-942.
[PMID: 30535489]
[26]
Chen, Z.; Liu, X.; Hu, Z.; Wang, Y.; Liu, M.; Liu, X.; Li, H.; Ji, R.; Guo, Q.; Zhou, Y. Identification and characterization of tumor suppressor and oncogenic miRNAs in gastric cancer. Oncol. Lett., 2015, 10(1), 329-336.
[http://dx.doi.org/10.3892/ol.2015.3179] [PMID: 26171025]
[27]
Cong, D.; He, M.; Chen, S.; Liu, X.; Liu, X.; Sun, H. Expression profiles of pivotal microRNAs and targets in thyroid papillary carcinoma: An analysis of The Cancer Genome Atlas. OncoTargets Ther., 2015, 8, 2271-2277.
[PMID: 26345235]
[28]
Yi, S.; Liu, G.; Wu, Y.; Liang, Q.; Li, L. Baicalein suppresses the growth of the human thyroid cancer cells by inducing mitotic catastrophe, apoptosis and autophagy via NF-kB signalling pathway. J. BUON, 2021, 25(1), 389-394.
[29]
Wang, B.; Mao, J.; Wang, B.; Wang, L.; Wen, H.; Xu, L.; Fu, J.; Yang, H. Exosomal miR-1910-3p promotes proliferation, metastasis, and autophagy of breast cancer cells by targeting MTMR3 and activating the NF-κB signaling pathway. Cancer Lett., 2020, 489, 87-99.
[http://dx.doi.org/10.1016/j.canlet.2020.05.038] [PMID: 32531321]
[30]
Baker, K.; Gordon, S.L.; Melland, H.; Bumbak, F.; Scott, D.J.; Jiang, T.J.; Owen, D.; Turner, B.J.; Boyd, S.G.; Rossi, M.; Al-Raqad, M.; Elpeleg, O.; Peck, D.; Mancini, G.M.S.; Wilke, M.; Zollino, M.; Marangi, G.; Weigand, H.; Borggraefe, I.; Haack, T.; Stark, Z.; Sadedin, S.; Tan, T.Y.; Jiang, Y.; Gibbs, R.A.; Ellingwood, S.; Amaral, M.; Kelley, W.; Kurian, M.A.; Cousin, M.A.; Raymond, F.L. SYT1-associated neurodevelopmental disorder: A case series. Brain, 2018, 141(9), 2576-2591.
[http://dx.doi.org/10.1093/brain/awy209] [PMID: 30107533]
[31]
Nord, H.; Hartmann, C.; Andersson, R.; Menzel, U.; Pfeifer, S.; Piotrowski, A.; Bogdan, A.; Kloc, W.; Sandgren, J.; Olofsson, T.; Hesselager, G.; Blomquist, E.; Komorowski, J.; von Deimling, A.; Bruder, C.E.G.; Dumanski, J.P.; de Ståhl, T.D. Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array. Neuro-oncol., 2009, 11(6), 803-818.
[http://dx.doi.org/10.1215/15228517-2009-013] [PMID: 19304958]

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