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miR-576-5p 通过靶向 NEGR1 促进结肠腺癌的侵袭性细胞行为。

miR-576-5p Facilitates Aggressive Cell Behaviors in Colon Adenocarcinoma via Targeting NEGR1.

机构信息

Department of Oncology and Hematology, The Second Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Crit Rev Eukaryot Gene Expr. 2022;32(7):25-33. doi: 10.1615/CritRevEukaryotGeneExpr.2022043160.

Abstract

The microRNA (miRNA) miR-576-5p was reported to facilitate tumor progression, but its underlying regulatory impacts on colon adenocarcinoma remain unknown. This work therefore attempted to examine the biological effects of miR-576-5p in colon adenocarcinoma. The Cancer Genome Atlas (TCGA) database was introduced to analyze miR-576-5p and NEGR1 messenger RNA (mRNA) expression levels between normal and cancer tissues. miR-576-5p and NEGR1 expression levels in colon adenocarcinoma cells and colon cells were evaluated with quantitative reverse transcription polymerase chain reaction (qRT-PCR). NEGR1 protein expression was examined by Western blot. Furthermore, colon adenocarcinoma cell behaviors were evaluated via CCK-8, wound-healing, Transwell, and hanging drop experiments. The interaction between miR-576-5p and NEGRI was verified by dual-luciferase assay. miR-576-5p was upregulated in colon adenocarcinoma, and miR-576-5p overexpression notably facilitated the proliferative, migratory, invasive abilities of colon adenocarcinoma cells. NEGR1 was newly identified as one target of miR-576-5p, and, miR-576-5p/NEGR1 axis was subsequently verified to modulate cell proliferative, migratory, invasive, and aggregate abilities. miR-576-5p facilitated aggressive progression of colon adenocarcinoma cells by targeting NEGR1, which could be an underlying therapeutic target for colon adenocarcinoma.

摘要

微小 RNA(miRNA)miR-576-5p 被报道可促进肿瘤进展,但它对结肠腺癌的潜在调节作用尚不清楚。因此,本研究试图研究 miR-576-5p 在结肠腺癌中的生物学效应。本研究引入癌症基因组图谱(TCGA)数据库分析正常组织和肿瘤组织中 miR-576-5p 和 NEGR1 信使 RNA(mRNA)的表达水平。采用实时定量逆转录聚合酶链反应(qRT-PCR)检测结肠腺癌细胞和结肠细胞中 miR-576-5p 和 NEGR1 的表达水平。采用 Western blot 检测 NEGR1 蛋白表达水平。进一步通过 CCK-8、划痕愈合、Transwell 和悬滴实验评估结肠腺癌细胞行为。采用双荧光素酶报告基因实验验证 miR-576-5p 和 NEGR1 之间的相互作用。miR-576-5p 在结肠腺癌中上调,miR-576-5p 过表达显著促进结肠腺癌细胞的增殖、迁移和侵袭能力。NEGR1 被新鉴定为 miR-576-5p 的一个靶基因,miR-576-5p/NEGR1 轴随后被证实可调节细胞增殖、迁移、侵袭和聚集能力。miR-576-5p 通过靶向 NEGR1 促进结肠腺癌细胞的侵袭性进展,这可能是结肠腺癌的一个潜在治疗靶点。

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