ATG9B-4 accelerates the proliferation and migration of liver cancer cells in an ARNTL–CDK5 pathway-dependent manner: A case–control study

Lnc ATG9B-4 aggravated the progression of liver cancer by up-regulating cyclin-dependent-kinase 5 (CDK5). It could be inferred that ATG9B-4 indirectly regulates the expression of CDK5 via lncRNA-mediated negative regulation of target genes. Therefore, the specific molecular mechanism by which ATG9B-4 regulates the malignant characteristics of liver cancer cells still needs further study. The differentially expressed genes were identified by mRNA sequencing in liver cancer cells transfected with or without ATG9B-4. Liver cancer cells were transfected with ATG9B-4, ARNTL, or si-CDK5. The expression of aryl basic helix-loop-helix ARNT like 1 (BMAL1, also known as ARNTL), CDK5, and ATG9B-4 was analyzed by real-time quantitative PCR and western blotting. The proliferation and invasion of the transfected cells were respectively analyzed by cell counting kit-8 and wound healing assays, respectively. The ARNTL expression was down-regulated in the liver cancer tissues and liver cancer cells transfected with ATG9B-4. Low ARNTL expression indicated poor overall survival in patients with liver cancer. The optical density of cells transfected with ATG9B-4 and ARNTL was significantly lower than that of cells transfected with ATG9B-4. The wound areas of cells transfected with ATG9B-4 and ARNTL were markedly wider than those of cells transfected with ATG9B-4. The expression of CDK5 was down-regulated in cells transfected with ARNTL. CDK5 knockdown partially attenuated the ATG9B-4-induced increase in proliferation and migration in liver cancer cells. ATG9B-4 deteriorated the proliferation and migration of liver cancer cells in an ARNTL-CDK5 pathway-dependent manner.