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

Gene. 2023 Aug 15:877:147570. doi: 10.1016/j.gene.2023.147570. Epub 2023 Jun 16.

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.

Keywords: Chemoresistance; FAM13A-AS1; HCC; PHOX2B; PPARγ; Ubiquitin.

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Drug Resistance, Neoplasm / genetics
  • GTPase-Activating Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • RNA, Long Noncoding* / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • PPAR gamma
  • RNA, Long Noncoding
  • MicroRNAs
  • Transcription Factors
  • FAM13A protein, human
  • GTPase-Activating Proteins