Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

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

Research Article

Dysregulation of miR-551b-5p and SETD2 Predicts Poor Prognosis and Promotes Migration and Invasion of Thyroid Cancers

Author(s): Anbing Dong, Ming Gao*, Xiangqian Zheng and Xianhui Ruan

Volume 23, Issue 11, 2023

Published on: 14 June, 2023

Page: [1400 - 1409] Pages: 10

DOI: 10.2174/1871530323666230417083509

Price: $65

Abstract

Objective: This study was to investigate the clinical significance of miR-551b-5p and SETD2 in thyroid cancers (TC) and their effects on the biological function of TC cells.

Methods: The expression level of miR-551b-5p and SETD2 in tumor/nontumor tissues and TC cell lines was measured by quantitative real-time polymerase chain reaction (RT-qPCR). Subsequently, the relationship between miR-551b-5p or SETD2 expression and the clinicopathological feature was detected by Chi-square analysis. Kaplan-Meier and multivariate Cox regression analyses were used to assess their prognostic values. Finally, the regulatory effects of miR-551b-5p and SETD2 on the proliferation, migration and invasion ability of TC cells were detected by CCK-8 and Transwell assays.

Results: Compared with non-tumor groups, the expression of miR-551b-5p was significantly increased in patients' tissues and TC cell lines, while SETD2 mRNA expression was decreased. Patients with up-regulated miR-551b-5p or downregulated SETD2 mRNA in TC showed more positive lymph node metastasis and advanced TNM stage. High miR-551b-5p expression level and low SETD2 mRNA level were related to poor survival rate. miR-551b-5p and SETD2 might be potential prognostic biomarkers for TC. miR-551b-5p knockdown can inhibit cell proliferation, migration and invasion by targeting SETD2.

Conclusion: miR-551b-5p and SETD2 may be valuable prognostic biomarkers and new therapeutic targets for TC.

Graphical Abstract

[1]
Cabanillas, M.E.; McFadden, D.G.; Durante, C. Thyroid cancer. Lancet, 2016, 388(10061), 2783-2795.
[http://dx.doi.org/10.1016/S0140-6736(16)30172-6] [PMID: 27240885]
[2]
Mulita, F.; Anjum, F. Thyroid Adenoma. In: StatPearls; StatPearls Publishing: Treasure Island (FL), 2022.
[3]
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]
[4]
Schlumberger, M.; Leboulleux, S. Current practice in patients with differentiated thyroid cancer. Nat. Rev. Endocrinol., 2021, 17(3), 176-188.
[http://dx.doi.org/10.1038/s41574-020-00448-z] [PMID: 33339988]
[5]
Davies, L.; Hoang, J.K. Thyroid cancer in the USA: Current trends and outstanding questions. Lancet Diabetes Endocrinol., 2021, 9(1), 11-12.
[http://dx.doi.org/10.1016/S2213-8587(20)30372-7] [PMID: 33220765]
[6]
Mulita, F.; Iliopoulos, F.; Tsilivigkos, C.; Tchabashvili, L.; Liolis, E.; Kaplanis, C. Cancer rate of Bethesda category II thyroid nodules. Med. Glas., 2022, 19(1), 1413-21.
[http://dx.doi.org/10.17392/1413-21]
[7]
Wang, J.; Yu, F.; Shang, Y.; Ping, Z.; Liu, L. Thyroid cancer: incidence and mortality trends in China, 2005–2015. Endocrine, 2020, 68(1), 163-173.
[http://dx.doi.org/10.1007/s12020-020-02207-6] [PMID: 32002755]
[8]
Prete, A.; Borges de Souza, P.; Censi, S.; Muzza, M.; Nucci, N.; Sponziello, M. Update on fundamental mechanisms of thyroid cancer. Front. Endocrinol., 2020, 11, 102.
[http://dx.doi.org/10.3389/fendo.2020.00102] [PMID: 32231639]
[9]
Araque, K.A.; Gubbi, S.; Klubo-Gwiezdzinska, J. Updates on the management of thyroid cancer. Horm. Metab. Res., 2020, 52(8), 562-577.
[http://dx.doi.org/10.1055/a-1089-7870]
[10]
Chmielik, E.; Rusinek, D.; Oczko-Wojciechowska, M.; Jarzab, M.; Krajewska, J.; Czarniecka, A. Heterogeneity of thyroid cancer. Pathobiology, 2018, 85(1-2), 117-129.
[http://dx.doi.org/10.1159/000486422]
[11]
Braun, J.; Hüttelmaier, S. Pathogenic mechanisms of deregulated microRNA expression in thyroid carcinomas of follicular origin. Thyroid Res., 2011, 4(S1), S1.
[http://dx.doi.org/10.1186/1756-6614-4-S1-S1]
[12]
Biswas, S. MicroRNAs as Therapeutic Agents: The future of the battle against cancer. Curr. Top. Med. Chem., 2019, 18(30), 2544-2554.
[http://dx.doi.org/10.2174/1568026619666181120121830] [PMID: 30457051]
[13]
Ahmed, A.A.; Essa, M.E.A. Potential of epigenetic events in human thyroid cancer. Cancer Genet., 2019, 239, 13-21.
[http://dx.doi.org/10.1016/j.cancergen.2019.08.006] [PMID: 31472323]
[14]
Saliminejad, K.; Khorram, K.H.R.; Soleymani, F., S.; Ghaffari, S.H. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J. Cell. Physiol., 2019, 234(5), 5451-5465.
[http://dx.doi.org/10.1002/jcp.27486] [PMID: 30471116]
[15]
Cao, J.; Zhang, M.; Zhang, L.; Lou, J.; Zhou, F.; Fang, M. Non-coding RNA in thyroid cancer - Functions and mechanisms. Cancer Lett., 2021, 496, 117-126.
[http://dx.doi.org/10.1016/j.canlet.2020.08.021] [PMID: 32949678]
[16]
Lu, T.X.; Rothenberg, M.E. MicroRNA. J. Allergy Clin. Immunol., 2018, 141(4), 1202-1207.
[http://dx.doi.org/10.1016/j.jaci.2017.08.034] [PMID: 29074454]
[17]
Abdullah, M.I.; Junit, S.M.; Ng, K.L.; Jayapalan, J.J.; Karikalan, B.; Hashim, O.H. Papillary thyroid cancer: Genetic alterations and molecular biomarker investigations. Int. J. Med. Sci., 2019, 16(3), 450-460.
[http://dx.doi.org/10.7150/ijms.29935] [PMID: 30911279]
[18]
Montero-Conde, C.; Graña-Castro, O.; Martín-Serrano, G.; Martínez-Montes, Á.M.; Zarzuela, E.; Muñoz, J.; Torres-Perez, R.; Pita, G.; Cordero-Barreal, A.; Leandro-García, L.J.; Letón, R.; López de Silanes, I.; Guadalix, S.; Pérez-Barrios, A.; Hawkins, F.; Guerrero-Álvarez, A.; Álvarez-Escolá, C.; Regojo-Zapata, R.M.; Calsina, B.; Remacha, L.; Roldán-Romero, J.M.; Santos, M.; Lanillos, J.; Jordá, M.; Riesco-Eizaguirre, G.; Zafon, C.; González-Neira, A.; Blasco, M.A.; Al-Shahrour, F.; Rodríguez-Antona, C.; Cascón, A.; Robledo, M. Hsa‐miR‐139‐5p is a prognostic thyroid cancer marker involved in HNRNPF‐mediated alternative splicing. Int. J. Cancer, 2020, 146(2), 521-530.
[http://dx.doi.org/10.1002/ijc.32622] [PMID: 31403184]
[19]
Liu, X.; Hu, M.; Zhang, Q.; Lai, J.; Liu, X. SETD2 an epigenetic tumor suppressor a focused review on GI tumor. Front. Biosci., 2020, 25(4), 781-797.
[http://dx.doi.org/10.2741/4834] [PMID: 31585917]
[20]
Pecce, V.; Verrienti, A.; Abballe, L.; Carletti, R.; Grani, G.; Falcone, R.; Ramundo, V.; Durante, C.; Di Gioia, C.; Russo, D.; Filetti, S.; Sponziello, M. Loss of function SETD2 mutations in poorly differentiated metastases from two Hürthle cell carcinomas of the thyroid. Cancers, 2020, 12(7), 1892.
[http://dx.doi.org/10.3390/cancers12071892] [PMID: 32674319]
[21]
Ab Mutalib, N.S.; Othman, S.N.; Mohamad, Y., A.; Abdullah, S., S.N.; Muhammad, R.; Jamal, R. Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis. PeerJ, 2016, 4, e2119.
[http://dx.doi.org/10.7717/peerj.2119] [PMID: 27350898]
[22]
Matsui, D.; Zaidi, A.H.; Martin, S.A.; Omstead, A.N.; Kosovec, J.E.; Huleihel, L.; Saldin, L.T.; DiCarlo, C.; Silverman, J.F.; Hoppo, T.; Finley, G.G.; Badylak, S.F.; Kelly, R.J.; Jobe, B.A. Primary tumor microRNA signature predicts recurrence and survival in patients with locally advanced esophageal adenocarcinoma. Oncotarget, 2016, 7(49), 81281-81291.
[http://dx.doi.org/10.18632/oncotarget.12832] [PMID: 27793030]
[23]
Wu, K.; Wang, L.; Fu, G.; Zheng, Y. Expression and clinical significance of microRNA-21-3p and microRNA-551-5p in patients with acute pancreatitis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2020, 32(4), 463-467.
[PMID: 32527354]
[24]
Kuśnierz-Cabala, B.; Nowak, E.; Sporek, M.; Kowalik, A.; Kuźniewski, M.; Enguita, F.J. Serum levels of unique miR-551-5p and endothelial-specific miR-126a-5p allow discrimination of patients in the early phase of acute pancreatitis. Pancreatology, 2015, 15(4), 344-51.
[http://dx.doi.org/10.1016/j.pan.2015.05.475]
[25]
Swierniak, M.; Wojcicka, A.; Czetwertynska, M.; Stachlewska, E.; Maciag, M.; Wiechno, W.; Gornicka, B.; Bogdanska, M.; Koperski, L.; de la Chapelle, A.; Jazdzewski, K. In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma. J. Clin. Endocrinol. Metab., 2013, 98(8), E1401-E1409.
[http://dx.doi.org/10.1210/jc.2013-1214] [PMID: 23783103]
[26]
Wei, Z.; Liu, Y.; Wang, Y.; Zhang, Y.; Luo, Q.; Man, X.; Wei, F.; Yu, X. Downregulation of Foxo3 and TRIM31 by miR-551b in side population promotes cell proliferation, invasion, and drug resistance of ovarian cancer. Med. Oncol., 2016, 33(11), 126.
[http://dx.doi.org/10.1007/s12032-016-0842-9] [PMID: 27743201]
[27]
Wang, J; Liu, H. miR-551b is associated with the poor prognosis and malignant development of papillary thyroid cancer through regulating ERBB4. Hormone Metab. Res., 2022, 54(2), 113-8.
[28]
Li, J.; Duns, G.; Westers, H.; Sijmons, R.; van den Berg, A.; Kok, K. SETD2: an epigenetic modifier with tumor suppressor functionality. Oncotarget, 2016, 7(31), 50719-50734.
[http://dx.doi.org/10.18632/oncotarget.9368] [PMID: 27191891]
[29]
Chen, R.; Zhao, W.; Fang, C.; Yang, X.; Ji, M. Histone methyltransferase SETD2: A potential tumor suppressor in solid cancers. J. Cancer, 2020, 11(11), 3349-3356.
[http://dx.doi.org/10.7150/jca.38391] [PMID: 32231741]
[30]
Tsang, J.Y.; Lai, S.T.; Ni, Y.B.; Shao, Y.; Poon, I.K.; Kwan, J.S.; Chow, C.; Shea, K.H.; Tse, G.M. SETD2 alterations and histone H3K36 trimethylation in phyllodes tumor of breast. Breast Cancer Res. Treat., 2021, 187(2), 339-347.
[http://dx.doi.org/10.1007/s10549-021-06181-z] [PMID: 33844099]
[31]
Chen, Z.; Raghoonundun, C.; Chen, W.; Zhang, Y.; Tang, W.; Fan, X.; Shi, X. SETD2 indicates favourable prognosis in gastric cancer and suppresses cancer cell proliferation, migration, and invasion. Biochem. Biophys. Res. Commun., 2018, 498(3), 579-585.
[http://dx.doi.org/10.1016/j.bbrc.2018.03.022] [PMID: 29522714]
[32]
Piva, F.; Santoni, M.; Matrana, M.R.; Satti, S.; Giulietti, M.; Occhipinti, G.; Massari, F.; Cheng, L.; Lopez-Beltran, A.; Scarpelli, M.; Principato, G.; Cascinu, S.; Montironi, R. BAP1, PBRM1 and SETD2 in clear-cell renal cell carcinoma: molecular diagnostics and possible targets for personalized therapies. Expert Rev. Mol. Diagn., 2015, 15(9), 1201-1210.
[http://dx.doi.org/10.1586/14737159.2015.1068122] [PMID: 26166446]
[33]
Kim, K.S.; Jeong, D.; Sari, I.N.; Wijaya, Y.T.; Jun, N.; Lee, S.; Yang, Y.G.; Lee, S.H.; Kwon, H.Y. miR551b regulates colorectal cancer progression by targeting the ZEB1 Signaling Axis. Cancers, 2019, 11(5), 735.
[http://dx.doi.org/10.3390/cancers11050735] [PMID: 31137914]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy