Long Non-coding RNA TMEM220-AS1 Suppressed Hepatocellular Carcinoma by Regulating the miR-484/MAGI1 Axis as a Competing Endogenous RNA.
Long Non-coding RNA TMEM220-AS1 Suppressed Hepatocellular Carcinoma by Regulating the miR-484/MAGI1 Axis as a Competing Endogenous RNA.
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DOI：
10.3389/fcell.2021.681529
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发表时间：
2021
影响因子：
5.5
通讯作者：
Cao S
中科院分区：
文献类型：
--
作者：
Cao C;Li J;Li G;Hu G;Deng Z;Huang B;Yang J;Li J;Cao S
长链非编码RNA（lncRNA）对多种生物学过程具有重要的调控作用。然而，TMEM 220-AS 1在肝细胞癌（HCC）中的作用仍不清楚。我们使用癌症基因组图谱（TCGA）数据库来分析差异表达的lncRNA。qRT-PCR用于验证大群体的结果。在HCC细胞中使用细胞计数试剂盒-8（CCK-8）、5-乙炔基-2 '-脱氧尿苷（EdU）、流式细胞术和Transwell测定来确定TMEM 220-AS 1对HCC细胞的体外作用。我们使用qRT-PCR和蛋白质印迹来鉴定上皮-间质转化（EMT）。此外，我们进行了生物信息学分析，蛋白质印迹，双荧光素酶报告基因测定，RNA下拉，和RNA结合蛋白免疫沉淀（RIP），以研究TMEM 220-AS 1功能的潜在分子机制。最后，在体内验证了TMEM 220-AS 1的功能。结果表明，TMEM 220-AS 1在HCC中以相当低的水平表达。TMEM 220-AS 1基因的敲除在体内外均能促进肝癌细胞的恶性表型和EMT。TMEM 220-AS 1主要在细胞质中检测到，作为miRNA海绵结合miR-484并促进膜相关鸟苷酸激酶、WW和PDZ结构域1（MAGI 1）的水平，从而抑制HCC细胞的恶性表型。总之，低水平的TMEM 220-AS 1通过miR-484/MAGI 1轴促进HCC中的增殖和转移。
Long non-coding RNAs (lncRNAs) have a considerable regulatory influence on multiple biological processes. Nevertheless, the role of TMEM220-AS1 in hepatocellular carcinoma (HCC) remains unclear. We used The Cancer Genome Atlas (TCGA) database to analyze the differentially expressed lncRNAs. qRT-PCR was used to verify the results for a large population. The in vitro effects of TMEM220-AS1 on HCC cells were determined using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, and Transwell assays in HCC cells. We used qRT-PCR and western blotting to identify the epithelial-mesenchymal transition (EMT). Moreover, we performed bioinformatics analysis, western blotting, dual luciferase reporter gene assay, RNA pull-down, and RNA binding protein immunoprecipitation (RIP) to investigate the underlying molecular mechanisms of TMEM220-AS1 function. Finally, the function of TMEM220-AS1 was verified in vivo. The results showed that TMEM220-AS1 was expressed at considerably low levels in HCC. It was demonstrated that malignant phenotypes and EMT of HCC cells were promoted by the knock down of TMEM220-AS1 both in vivo and in vitro. TMEM220-AS1, which was detected primarily in the cytoplasm, functioned as an miRNA sponge to bind miR-484 and promote the level of membrane-associated guanylate kinase, WW, and PDZ domain containing 1 (MAGI1), thereby curbing the malignant phenotypes of HCC cells. In conclusion, low levels of TMEM220-AS1 promote proliferation and metastasis through the miR-484/MAGI1 axis in HCC.
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影响因子：
6.2
作者：
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