LncRNA FAM13A-AS1, transcriptionally regulated by PHOX2B, modulates hepatocellular carcinoma chemoresistance via stabilizing PPARγ

Abstract

Hepatocellular carcinoma (HCC) is a major global public health concern, with approximately 79 million new cases and 75 million HCC-related deaths occurring annually worldwide. Among the drugs, cisplatin (DDP) is considered a cornerstone and has been shown to significantly inhibit cancer progression. However, the mechanism underlying DDP-resistance in HCC remains unclear. This study aimed to identify a novel lncRNA. FAM13A Antisense RNA 1 (FAM13A-AS1), that promotes the proliferation of DDP-resistant HCC cells and to elucidate its downstream and upstream mechanisms in the progression of HCC DDP-resistance. Our results suggest that FAM13A-AS1 interacts directly with Peroxisome Proliferator Activated Receptor γ (PPARγ), stabilizing its protein through de-ubiquitination. Moreover, our findings indicate that Paired Like Homeobox 2B (PHOX2B) transcriptionally regulates the expression of FAM13A-AS1 in HCC cells. These results shed new light on the understanding of the progression of HCC DDP-resistance.