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长链非编码 RNA(lncRNA)MT1JP 通过调节 miRNA-423-3p/Bim 轴抑制肺癌的生物学活性。

Long-Chain Non-Coding RNA (lncRNA) MT1JP Suppresses Biological Activities of Lung Cancer by Regulating miRNA-423-3p/Bim Axis.

机构信息

Department of Respiration, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China (mainland).

出版信息

Med Sci Monit. 2019 Jul 10;25:5114-5126. doi: 10.12659/MSM.914387.

Abstract

BACKGROUND This study aimed to explain the effects and mechanism of MT1JP in lung cancer development and treatment. MATERIAL AND METHODS Thirty non-small cell lung cancer (NSCLC) (stages I-II, 17 cases; stages III-IV, 13 cases) and adjacent normal tissues were obtained. MT1JP and miRNA-423-3p levels were assessed by hybridization and Bim protein expression by immunohistochemistry, and the correlations determined were analyzed. Cell proliferation was determined using MTT and colony formation assay, and cell apoptosis was measured using flow cytometry. A549 cell invasion and migration were assessed by Transwell migration and scratch wound healing assays. Relative mRNA and protein expressions were assessed using real-time polymerase chain reaction and western blotting. Correlations between miRNA-423-3p and Bim protein were investigated using luciferase activity assay, and Bim protein expression was evaluated using western blotting. RESULTS MT1JP, miRNA-423-3p, and Bim expressions in NSCLC cancer tissues and those in adjacent cancer tissues were significantly different (<0.01 or <0.001) with increasing stage. Compared with those in the normal control (NC) group, cell proliferation rates were significantly suppressed (<0.01 or <0.001) and cell apoptosis rates significantly increased (<0.01 or <0.001) in the miRNA inhibitor and lncRNA+miRNA inhibitor groups. Invasion cell numbers and wound healing rates were also significantly inhibited in the miRNA inhibitor and lncRNA+miRNA inhibitor groups (<0.01 or <0.001) compared with those in the NC group. CONCLUSIONS The lncRNA MT1JP suppresses NSCLC biological activities by regulating the miRNA-423-3p/Bim axis.

摘要

背景 本研究旨在解释 MT1JP 在肺癌发展和治疗中的作用和机制。

材料和方法 收集 30 例非小细胞肺癌(NSCLC)(I-II 期 17 例,III-IV 期 13 例)及癌旁正常组织。通过杂交评估 MT1JP 和 miRNA-423-3p 水平,免疫组化评估 Bim 蛋白表达,并分析确定的相关性。MTT 和集落形成实验检测细胞增殖,流式细胞术检测细胞凋亡。Transwell 迁移和划痕愈合实验检测 A549 细胞侵袭和迁移。实时聚合酶链反应和 Western blot 检测相对 mRNA 和蛋白表达。通过荧光素酶活性测定研究 miRNA-423-3p 和 Bim 蛋白之间的相关性,Western blot 检测 Bim 蛋白表达。

结果 NSCLC 癌组织和癌旁组织中 MT1JP、miRNA-423-3p 和 Bim 蛋白表达差异有统计学意义(<0.01 或 <0.001),且随分期增加而升高。与正常对照组(NC 组)相比,miRNA 抑制剂和 lncRNA+miRNA 抑制剂组细胞增殖率显著降低(<0.01 或 <0.001),细胞凋亡率显著升高(<0.01 或 <0.001)。miRNA 抑制剂和 lncRNA+miRNA 抑制剂组侵袭细胞数和伤口愈合率也明显低于 NC 组(<0.01 或 <0.001)。

结论 lncRNA MT1JP 通过调节 miRNA-423-3p/Bim 轴抑制 NSCLC 生物学活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e616/6637816/d8ec172636df/medscimonit-25-5114-g001.jpg

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