A curcumin analog GL63 inhibits the malignant behaviors of hepatocellular carcinoma by inactivating the JAK2/STAT3 signaling pathway via the circular RNA zinc finger protein 83/microRNA‐324‐5p/cyclin‐dependent kinase 16 axis

BACKGROUND AND AIM: (1E,4E)‐1,5‐bis(2‐bromophenyl) penta‐1,4‐dien‐3‐one (GL63) is a curcumin analog that can protect against carcinogenesis in hepatocellular carcinoma (HCC). The aim of this study was to explore the molecular mechanism of GL63 in HCC. METHODS: Cell viability was examined by cell counting kit‐8 (CCK‐8) assay. Circular RNA zinc finger protein 83 (circZNF83), microRNA‐324‐5p (miR‐324‐5p), and cyclin‐dependent kinase 16 (CDK16) levels were measured via the quantitative real‐time polymerase chain reaction (qRT‐PCR). Cell proliferation was assessed using colony formation assay. Flow cytometry was performed for detecting cell cycle and apoptosis. Protein analysis was conducted by western blot. Cell migration and invasion were determined using transwell assay. Target relation was analyzed using dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays. The function of GL63 in vivo was researched by xenograft model in mice. RESULTS: GL63 inhibited the circZNF83 expression in HCC cells. CircZNF83 overexpression attenuated the inhibitory effects of GL63 on HCC cell growth, cell cycle progression, migration, and invasion but the promoting effect on cell apoptosis. CircZNF83 served as a sponge of miR‐324‐5p and circZNF83/miR‐324‐5p axis was involved in the functional regulation of GL63 in HCC progression. Moreover, CDK16 was a downstream target of miR‐324‐5p and circZNF83 could regulate the CDK16 expression by sponging miR‐324‐5p. The anti‐tumor function of GL63 was also related to the miR‐324‐5p/CDK16 axis. In addition, GL63 inactivated the JAK2/STAT3 pathway via downregulating circZNF83 to mediate the miR‐324‐5p/CDK16 axis. GL63 also repressed tumor growth in vivo through the circZNF83/miR‐324‐5p/CDK16‐mediated JAK2/STAT3 signal inhibition. CONCLUSION: This study suggested GL63 impeded the HCC development by blocking the JAK2/STAT3 signaling pathway via mediating the circZNF83/miR‐324‐5p/CDK16 axis.