LncRNA-MIAT通过抑制miR-519d-3p激活EZH2促进甲状腺癌的恶性行为

doi:10.3969/j.issn.1006-6233.2023.08.01

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Abstract Objective: To investigate the regulation and molecular mechanism of long non-coding RNA MIAT (LncRNA-MIAT) on proliferation, apoptosis, migration and invasion of thyroid cancer cells. Methods: The expression of LncRNA-MIAT and histone methyltransferase 2 (EZH2) in thyroid cancer was analyzed by Cancer Genome Atlas (TCGA) and thyroid cancer (THCA) mRNA-seq data. Human normal thyroid cell line Nthy-ori 3-1 and human thyroid cancer cell line FTC-133 were used as target cells. The mRNA expression levels of LncRNA-MIAT, miR-519d-3p and EZH2 were detected by qPCR. RNA fluorescence in situ hybridization (FISH) was used to detect the localization of LncRNA-MIAT in FTC-133 cells, and Western blot was used to detect the expression of EZH2 protein. Luciferase reporter gene was used to detect LncRNA-MIAT and miR-519d-3p and the direct effect of miR-519d-3p on EZH2. FTC-133 cells were divided into 6 groups (control group, Empty vector group, LncRNA-MIAT group (LncRNA-MIAT group), miR-519d-3p inhibitor group (miR-519d-3p group), EZH2 inhibitor EPZ-6438 treatment group (EPZ-6438 group), miR-519d-3p inhibitor combined with overexpression of LncRNA-MIAT group (LncRNA-MIAT+miR-519d-3p inhibitor group)]. Cell proliferation was detected by Edu kit and plate cloning. Apoptosis was detected by flow cytometry. Cell behavior was detected by Transwell cell migration and invasion assay. Results: The expressions of LncRNA-MIAT and EZH2 in thyroid carcinorna tissues and cells were up-regulated, and there was a positive correlation between the two (r=0.466, P<0.05). The expression of miR-519d-3p was down-regulated in FTC-133 cells (P<0.05). Double luciferase reporter assay showed that the target gene of miR-519d-3p was EZH2, and LncRNA-MIAT targeted inhibition of miR-519d-3p to activate EZH2. Compared with Empty vector group, the percentage of Edu positive cells, the number of cell clones, the number of cell invasion and migration in LncRNA-MIAT group and miR-519d-3p inhibitor group were significantly up-regulated (P<0.05), and the cell apoptosis rate was decreased (P<0.05). EZH2 inhibitor EPZ-6438 decreased the percentage of Edu positive cells, the number of cell clones, the number of cell invasion and migration (P<0.05), and increased the rate of apoptosis (P<0.05). Compared with LncRNA-MIAT group or miR-519d-3p inhibitor group, the Edu positive cell percentage, cell clone number, cell invasion and migration number of LncRNA-MIAT+miR-519d-3p inhibitor group were significantly up-regulated (P<0.05), respectively. The apoptosis rate was decreased (P<0.05). Conclusion: LncRNA-MIAT can promote the malignant behavior of thyroid cancer by inhibiting the activation of EZH2 by miR-519d-3p.

Key words： Thyroid carcinoma LncRNA-MIAT miR-519d-3p Histone methylated transferase 2 Cell malignant behavior

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	WUPUER Yimaer
	WANG Huguo

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WUPUER Yimaer,WANG Huguo. LncRNA-MIAT Promotes Malignant Behavior of Thyroid Cancer by Inhibiting miR-519d-3p to Activate EZH2[J]. HeBei Med, 2023, 29(8): 1233-1240.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.08.01 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I8/1233

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