Circular RNA MYLK Promotes Hepatocellular Carcinoma Progression Through the miR29a/KMT5C Signaling Pathway
Circular RNA MYLK Promotes Hepatocellular Carcinoma Progression Through the miR29a/KMT5C Signaling Pathway
复制标题
DOI：
10.2147/ott.s258715
复制
发表时间：
2020-01-01
影响因子：
4
通讯作者：
Wu, Linquan
中科院分区：
文献类型：
--
作者：
Gao, Jun;Li, Enliang;Wu, Linquan
目的：本研究旨在探讨circMYLK（hsa_circ_0002768）环状RNA在肝细胞癌（HCC）发生发展中的作用及circMYLK/miR-29 a/KMT 5C轴的可能机制。此外，还探索了一种可能受circMYLK调控的miRNA（miR-29 a），证实了miR-29 a与KMT 5C之间的靶向关系。使用FISH、qRT-PCR、Western印迹和双荧光素酶报告基因测定来检查参与HCC发展的circMYLK/miR 29 a/KMT 5C信号传导途径。此外，将HCC细胞植入裸鼠皮下以测试circMYLK在肿瘤生长中的作用。结果：确定circMYLK在HCC组织和细胞中显著上调。抑制circMYLK抑制HCC细胞增殖、迁移和侵袭，同时增加凋亡。此外，FISH、qRT-PCR和Western印迹以及双荧光素酶报告基因分析显示，circMYLK可以与miR-29 a结合。在拯救实验中，miR-29 a有可能消除肝癌中circMYLK敲低的抑制作用。此外，发现miR-29 a靶向KMT 5C基因，该基因受circMYLK正调控。最后，裸鼠致瘤性试验表明，注射circMYLK siRNA到裸鼠体内显著抑制异种移植瘤形成invivo.Conclusion：我们目前的研究表明，circMYLK促进肝癌进展作为一个竞争性的内源性RNA的miR-29 a，调节下游癌基因KMT 5C。
Purpose: This study aimed to investigate the functions of the circular RNA circMYLK (hsa_circ_0002768) in the development of hepatocellular carcinoma (HCC) and to identify the underlying mechanisms of the circMYLK/miR29a/KMT5C axis.Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to explore the expressions of circMYLK, miR-29a and KMT5C in HCC tissues and cells. A potential miRNA (miR-29a) regulated by circMYLK was also explored, and the target relationship between miR-29a and KMT5C was confirmed. FISH, qRT-PCR, Western blotting, and dual-luciferase reporter assays were used to examine the circMYLK/miR29a/KMT5C signaling pathways involved in HCC development. Additionally, HCC cells were implanted into nude mice subcutaneously to test the role of circMYLK in tumor growth.Results: circMYLK was determined to be significantly upregulated in HCC tissues and cells. Suppression of circMYLK repressed HCC cell proliferation, migration, and invasion while increasing apoptosis. In addition, FISH, qRT-PCR, and Western blotting, as well as dual-luciferase reporter assays, revealed that circMYLK could bind to miR-29a. In rescue experiments, miR-29a had the potential to eliminate the inhibitory effect of circMYLK knockdown in HCC. Moreover, miR-29a was found to target the KMT5C gene, which was positively regulated by circMYLK. Finally, a nude mouse tumorigenicity assay showed that injection of circMYLK siRNA into nude mice drastically suppressed xenograft tumor formation in vivo.Conclusion: Our current study demonstrated that circMYLK promotes HCC progression by acting as a competing endogenous RNA of miR-29a, which regulates the downstream oncogene KMT5C.