Overexpression of lncRNA MT1JP Mediates Apoptosis and Migration of Hepatocellular Carcinoma Cells by Regulating miR-24-3p
Overexpression of lncRNA MT1JP Mediates Apoptosis and Migration of Hepatocellular Carcinoma Cells by Regulating miR-24-3p
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DOI：
10.2147/cmar.s249582
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Qu, Fan
中科院分区：
文献类型：
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作者：
Shan, Qiu-Li;Chen, Ning-Ning;Qu, Fan
目的：本研究旨在探讨MT 1 JP长链非编码RNA对肝癌细胞凋亡和迁移的影响。我们用MT 1 JP和miR-24- 3 p转染肝细胞癌细胞，并评估其表达及其对凋亡和迁移的影响。结果：MT 1 JP在肝癌组织中表达下调（P < 0.05），而miR-24- 3 p在肝癌组织中表达上调（P < 0.05）。血清MT 1 JP水平与肿瘤大小、甲胎蛋白（AFP）、TNM分期、分化程度、淋巴结转移有关。MT 1 JP过表达和miR-24- 3 p抑制均抑制细胞增殖和迁移，并增加凋亡率。细胞迁移相关蛋白MMP-2、MMP-9的表达明显下调（P < 0.05）。他们上调Bcl-2相关的X蛋白（Bax）和半胱氨酸蛋白酶特异性蛋白酶（Caspase-3和-9）蛋白的表达，这些蛋白参与细胞凋亡。降低B细胞淋巴瘤/白血病-2（Bcl-2; P < 0.05）的表达。使用双荧光素酶基因报告基因测定和RNA结合蛋白共免疫沉淀鉴定MT 1 JP和miR-24- 3 p之间的靶向关系。MT 1 JP过表达显著下调miR-24- 3 p表达（P < 0.05）。肝癌组织中MT 1 JP与miR-24- 3 p表达呈负相关（r =-0.561，P < 0.001; Pearson.2检验）。结论：MT 1 JP在低水平表达时，通过调控miR-24 - 3 p参与肝癌细胞的增殖、凋亡和迁移。
Objective: This study aimed to determine the effects of the long non-coding (lnc) RNA MT1JP on the apoptosis and migration of hepatocellular carcinoma cells.Patients and Methods: Patients with liver cancer admitted to the Second People's Hospital of Liaocheng were included in this study. We transfected hepatocellular carcinoma cells with MT1JP and miR-24-3p and assessed their expression and effects on apoptosis and migration. Correlations were verified using a dual-luciferase reporter and RNA-binding protein coimmunoprecipitation.Results: The expression of MT1JP was downregulated (P < 0.05), whereas that of miR-24-3p was upregulated in liver cancer. Serum MT1JP levels were correlated with tumor size, alpha-fetoprotein (AFP), TNM stage, differentiation, and lymph node metastasis. Both MT1JP overexpression and miR-24-3p inhibition inhibited cellular proliferation and migration and increased apoptosis rates. They significantly downregulated expression of the cell migration-associated proteins matrix metalloproteinase -2, -9 (MMP-2, MMP-9) (P < 0.05). They upregulated the expression of Bcl-2-related X protein (Bax) and cysteinyl aspartate-specific proteinases (Caspase-3 and -9) proteins that are involved in apoptosis. They decreased expression of B-cell lymphoma/leukemia-2 (Bcl-2; P < 0.05). A target relationship between MT1JP and miR-24-3p was identified using dual-luciferase gene reporter assays and RNA-binding protein coimmunoprecipitations. MT1JP overexpression significantly downregulated miR-24-3p expression (P < 0.05). MT1JP and miR-24-3p expression were negatively correlated in liver cancer tissues (r = -0.561, P < 0.001; Pearson.2 tests). Rescue experiments showed that upregulating miR-24-3p expression could counteract MT1JP overexpression in hepatocellular carcinoma cells.Conclusion: MT1JP, even when expressed at low levels, participates in the proliferation, apoptosis, and migration of liver cancer cells by regulating miR-24-3p.