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miR-139-3p/驱动蛋白家族成员 18B 轴抑制胃癌的恶性进展。

miR-139-3p/Kinesin family member 18B axis suppresses malignant progression of gastric cancer.

机构信息

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China.

Department of Breast Surgery, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China.

出版信息

Bioengineered. 2022 Feb;13(2):4528-4536. doi: 10.1080/21655979.2022.2033466.

Abstract

miR-139-3p exerts tumor-suppressing functions in various cancers. We analyzed and identified that miR-139-3p expression was notably low in gastric cancer (GC) via edgeR differential analysis based on The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction (qRT-PCR) assay. The binding relationship between Kinesin Family Member 18B (KIF18B) and miR-139-3p was predicted by bioinformatics databases, and verified through dual-luciferase assay. Western blot and qRT-PCR results also indicated that miR-139-3p restrained KIF18 expression at mRNA and protein levels. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, transwell, flow cytometry assays were introduced to evaluate cell proliferation, migration, invasion, and cell cycle, respectively, where the results indicated that upregulating miR-139-3p inhibited proliferative, migratory, and invasive abilities of GC cells, while caused cell-cycle arrest. Moreover, the results of rescue experiments illustrated that miR-139-3p hampered the progression of GC cells by targeting and suppressing KIF18B. To sum up, we concluded that miR-139-3p suppressed GC progression by targeting KIF18B.

摘要

miR-139-3p 在多种癌症中发挥肿瘤抑制功能。我们通过基于癌症基因组图谱数据库的 edgeR 差异分析和定量实时聚合酶链反应 (qRT-PCR) 检测分析,发现 miR-139-3p 在胃癌 (GC) 中的表达明显降低。生物信息学数据库预测了 Kinesin Family Member 18B (KIF18B) 和 miR-139-3p 之间的结合关系,并通过双荧光素酶报告基因实验进行了验证。Western blot 和 qRT-PCR 结果也表明 miR-139-3p 在 mRNA 和蛋白水平上抑制 KIF18 的表达。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐、划痕愈合、Transwell 侵袭实验和流式细胞术分别用于评估细胞增殖、迁移、侵袭和细胞周期,结果表明上调 miR-139-3p 抑制 GC 细胞的增殖、迁移和侵袭能力,同时导致细胞周期停滞。此外,挽救实验的结果表明,miR-139-3p 通过靶向和抑制 KIF18B 来阻碍 GC 细胞的进展。综上所述,我们得出结论,miR-139-3p 通过靶向 KIF18B 抑制 GC 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8b/8974075/0c7cbe973dae/KBIE_A_2033466_UF0001_B.jpg

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