miR-183-5p 靶向调控 ABAT 对肝癌细胞功能的影响
ABAT targeted by miR-183-5p regulates cell functions in liver cancer.
机构信息
Zhejiang University School of Medicine, Zhejiang 310011, PR China; Department of General Surgery, The Second Affiliated Hospital of Shantou University Medical College, Guangdong Province 515041, PR China.
Department of Gastrointestinal Surgery, Taizhou Hospital, Zhejiang University, Zhejiang 310011, PR China; Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Zhejiang 310016, PR China.
出版信息
Int J Biochem Cell Biol. 2021 Dec;141:106116. doi: 10.1016/j.biocel.2021.106116. Epub 2021 Nov 3.
BACKGROUND
Liver cancer triggers a considerable number of global deaths. This work focused on mechanisms as well as impacts of ABAT in liver cancer.
METHODS
Differentially expressed mRNAs in liver cancer were analyzed with The Cancer Genome Atlas (TCGA) database to determine and evaluate the prognostic significance of the target gene ABAT. ABAT was overexpressed to explore its effect on liver cancer. Furthermore, the targeted regulation between miR-183-5p and ABAT was verified through dual-luciferase method. The effects of their expression on liver cancer functions were detected by cell functional experiments like Cell Counting Kit-8 (CCK8), Transwell and flow cytometry. Lastly, the inhibitory effect of ABAT on the tumor was proved in nude mice in vivo.
RESULTS
At tissue and cell levels, ABAT was inactivated in liver cancer, and liver cancer patients with lowly expressed ABAT had poor prognosis. Overexpressing ABAT could inhibit cancer cell behaviors, and suppress tumorigenesis in nude mice. Meanwhile, overexpressed ABAT could upregulate E-cadherin in liver cancer cells, while downregulate MMP-9, Vimentin, MMP-2, N-cadherin, Ki67. Of note, miR-183-5p was highly expressed in liver cancer tissue and cells, which could target and downregulate ABAT expression. It was indicated by rescue assay that lowly expressed miR-183-5p could repress functions of liver cancer cells, while such inhibitory effect could be recovered by ABAT silencing.
CONCLUSION
Downstream of miR-183-5p, ABAT was targeted to mediate progression of liver cancer.
背景
肝癌引发了大量的全球死亡。本研究聚焦于 ABAT 在肝癌中的作用机制和影响。
方法
利用癌症基因组图谱（TCGA）数据库分析肝癌中差异表达的 mRNA，以确定和评估靶基因 ABAT 的预后意义。过表达 ABAT 以探索其对肝癌的影响。此外，通过双荧光素酶法验证 miR-183-5p 与 ABAT 之间的靶向调控关系。通过细胞计数试剂盒-8（CCK8）、Transwell 和流式细胞术等细胞功能实验检测其表达对肝癌功能的影响。最后，在体内裸鼠中证明 ABAT 对肿瘤的抑制作用。
结果
在组织和细胞水平上，ABAT 在肝癌中失活，ABAT 低表达的肝癌患者预后不良。过表达 ABAT 可抑制癌细胞行为，并抑制裸鼠肿瘤发生。同时，过表达 ABAT 可上调肝癌细胞中的 E-钙黏蛋白，下调 MMP-9、波形蛋白、MMP-2、N-钙黏蛋白、Ki67。值得注意的是，miR-183-5p 在肝癌组织和细胞中高表达，可靶向并下调 ABAT 表达。通过挽救实验表明，miR-183-5p 低表达可抑制肝癌细胞的功能，而 ABAT 沉默可恢复这种抑制作用。
结论
miR-183-5p 下游靶向 ABAT 介导肝癌进展。
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