Abstract: Objective The aim of this study was to investigate the molecular regulatory mechanism of cancer susceptibility candidate 15 (CASC15),a long-stranded non-coding RNA (lncRNA),in hepatocellular carcinoma (HCC). Methods Bioinformatics methods were used to predict the expression of target genes and analyze the relationship between the expression of target genes and the survival time of patients;Hepatocellular carcinoma tissues and adjacent tissues from patients with HCC were collected;CCK-8,Transwell,and flow cytometry experiments were used to detect proliferation,invasion,migration and apoptosis of SMMC7721 cells and Huh-7 cells;The dual-luciferase assay was used to detect the targeting relationship between miR-144-3p and CASC15,as well as leucine rich repeat containing protein 1 (LRRC1);RT-qPCR and Western blot were used to detect mRNA and protein expression of target genes;Immunofluorescence was used for protein localization of target genes;Replicate experiment was performed to verify the effect of CASC15/miR-144-3p/LRRC1 on the progression of HCC.In vivo experiment was performed to verify the effect of CASC15 on HCC progression. Results TCGA database and RT-qPCR assay showed high expression of CASC15,low expression of miR-144-3p,and high expression of LRRC1 in HCC tissues and cells (P＜0.05).The results of cell function experiments on proliferation,invasion and migration showed that CASC15 and LRRC1 played a promoting role in tumor development,while miR-144-3p had an inhibitory effect,consistent with the results of apoptosis experiments (P＜0.05).Cell function experiments showed that CASC15 inhibited miR-144-3p function,miR-144-3p inhibited LRRC1,and CASC15 bound to miR-144-3p,leading to the upregulation of LRRC1.The replicate experimental results indicated that CASC15 promoted LRRC1 expression through inhibiting miR-144-3p,thereby promoting HCC cell proliferation,invasion and migration,and inhibiting apoptosis. Conclusion CASC15 may promote HCC progression by regulating the miR-144-3p/LRRC1 axis.

Key words: Cancer susceptibility gene 15, miR-144-3p, Leucine-rich repeative sequence protein 1, Hepatocellular carcinoma cells, Cell biological function