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miRNA-383-5p Regulated Migration and Invasion of Tumor Cells by Inhibiting NCKAP1 Expression in Gastric Cancer
Biochemical Genetics ( IF 2.4 ) Pub Date : 2024-04-16 , DOI: 10.1007/s10528-024-10804-7
Chen Wang , Pan Wang , Yuan Tian , Cuijuan Lu , Lixia Liu , Jianguo Wu , Yanan Wang , Jinghua Li

Gastric cancer (GC) is the second deadliest disease in Asia, so it is crucial to find its promising therapeutic targets. The expression profile data of miR383-5p in the Cancer Genome Atlas (TCGA) were analyzed. The expression levels of miR383-5p in the collected clinical tissue samples and peripheral blood samples were examined by qPCR, and the relationship between its expression and the clinical data of patients was evaluated. MiR383-5p was overexpressed in the AGS cells, and cell biology assays, such as Transwell, were performed to detect the cell proliferation, migration, invasion and other cell biology abilities of miR383-5p. Target prediction and dual luciferase reporter gene assay were performed to find and validate the target genes of miR383-5p. The expression and activity of MMP and related proteins after overexpression of miR383-5p and NCKAP1 were detected by WB and gelatin zymography assay. The expression of miR383-5p was down-regulated in GC tissues, and its low expression was associated with lymph node metastasis. Restoration of miR383-5p expression in GC cells can inhibit the invasion and migration abilities of GC cells. MiR383-5p negatively regulated NCKAP1 through direct interaction with the 3’UTR sequence of NCKAP1. The overexpression of NCKAP1 can improve the migration and invasion abilities of GC cells, whereas overexpression of miR383-5p can inhibit growth of the aforementioned abilities of GC cells induced by NCKAP1 overexpression. The overexpression of NCKAP1 can increase the expression level and activity of MMP2, while the overexpression of miR383-5p can inhibit the increase of MMP2 expression level and activity in GC cells induced by NCKAP1 overexpression. NCKAP1 is a target gene of miR383-5p, and miR383-5p could be a valuable therapeutic target for stomach adenocarcinoma.



中文翻译:

胃癌中miRNA-383-5p通过抑制NCKAP1表达调节肿瘤细胞的迁移和侵袭

胃癌(GC)是亚洲第二大致命疾病,因此找到有希望的治疗靶点至关重要。分析了癌症基因组图谱(TCGA)中miR383-5p的表达谱数据。采用qPCR检测收集的临床组织样本和外周血样本中miR383-5p的表达水平,评估其表达与患者临床资料的关系。 miR383-5p在AGS细胞中过表达,通过Transwell等细胞生物学实验检测miR383-5p的细胞增殖、迁移、侵袭等细胞生物学能力。进行靶点预测和双荧光素酶报告基因测定来寻找和验证miR383-5p的靶基因。采用WB和明胶酶谱法检测miR383-5p和NCKAP1过表达后MMP及相关蛋白的表达和活性。 miR383-5p在GC组织中表达下调,其低表达与淋巴结转移相关。恢复GC细胞中miR383-5p的表达可以抑制GC细胞的侵袭和迁移能力。 MiR383-5p 通过与 NCKAP1 的 3'UTR 序列直接相互作用来负向调节 NCKAP1。 NCKAP1的过表达可以提高GC细胞的迁移和侵袭能力,而miR383-5p的过表达可以抑制NCKAP1过表达诱导的GC细胞的上述能力的生长。 NCKAP1的过表达可以增加MMP2的表达水平和活性,而miR383-5p的过表达可以抑制NCKAP1过表达诱导的GC细胞中MMP2表达水平和活性的增加。 NCKAP1是miR383-5p的靶基因,miR383-5p可能成为胃腺癌的一个有价值的治疗靶点。

更新日期:2024-04-17
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