Oncogenic lncRNA BBOX1-AS1 promotes PHF8-mediated autophagy and elicits sorafenib resistance in hepatocellular carcinoma

Some long non-coding RNAs (lncRNAs) have been docu-mented to be involved in cancer progression and anticancer drug resistance in hepatocellular carcinoma (HCC). Thus, ap-proaches designed to target these genes may facilitate the devel-opment of promising strategies for treating HCC. Previously, we showed that lncRNA BBOX1-AS1 was highly expressed and played an oncogenic role in HCC. However, the potential functions and mechanisms through which BBOX1-AS1 regu-lates HCC progression and drug resistance remain unclear. This study revealed that BBOX1-AS1 could promote tumor progression, autophagy, and drug resistance by upregulating PHF8 in HCC cells. Mechanistically, BBOX1-AS1 enhanced the stability of PHF8 mRNA by targeting the PHF8 inhibitor miR-361-3p to regulate tumor progression and autophagy in HCC. The functional rescue experiments showed that PHF8 acted as a key factor in regulating the biological effects induced by BBOX1-AS1 and miR-361-3p in HCC, indicating that BBOX1-AS1 promotes tumor progression and sorafenib resis-tance by regulating miR-361-3p/PHF8. Finally, mouse tumor models and patient-derived organoid models were established to further confirm these findings. Taken together, the results demonstrate that BBOX1-AS1 promotes HCC progression and sorafenib resistance via the miR-361-3p/PHF8 axis.

Automated summary

This study found that the lncRNA BBOX1-AS1 promotes tumor progression and drug resistance in HCC by upregulating PHF8. BBOX1-AS1 enhances the stability of PHF8 mRNA by targeting miR-361-3p, leading to tumor progression and autophagy. These findings suggest that BBOX1-AS1 promotes HCC progression and sorafenib resistance through the miR-361-3p/PHF8 axis.