OncoTargets and Therapy (Aug 2020)
Circular RNA MYLK Promotes Hepatocellular Carcinoma Progression Through the miR29a/KMT5C Signaling Pathway
Abstract
Jun Gao,1,* Enliang Li,1,* Weiwei Liu,1,* Qingping Yang,2 Chunyan Xie,3 Jiyuan Ai,1 Fan Zhou,1 Wenjun Liao,1 Linquan Wu1 1Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Assisted Reproductive, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linquan Wu; Wenjun LiaoDepartment of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 791 86311529Fax +86 791 86262262Email [email protected]; [email protected]: 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.Keywords: hepatocellular carcinoma, circMYLK, miR-29a, KMT5C
