PRR34-AS1 promotes exosome secretion of VEGF and TGF-β via recruiting DDX3X to stabilize Rab27a mRNA in hepatocellular carcinoma

J Transl Med. 2022 Oct 27;20(1):491. doi: 10.1186/s12967-022-03628-9.

Abstract

Background: Exosomes are deemed to be an important tool of intercellular communicators in cancer cells. Our study investigated the role of PRR34 long non-coding RNA antisense RNA 1 (PRR34-AS1) in regulating exosome secretion in hepatocellular carcinoma (HCC) cells.

Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) analyzed the expression of PRR34-AS1. We assessed the function of PRR34-AS1 on the biological changes of THLE-3 cells and HCC cells. The downstream interaction between RNAS was assessed by mechanistic experiments.

Results: PRR34-AS1 expression was upregulated in HCC cells in comparison to THLE-3 cells. PRR34-AS1 depletion repressed HCC cell proliferation, migration and invasion as well as EMT phenotype, while PRR34-AS1 up-regulation accelerated the malignant phenotypes of THLE-3 cells. PRR34-AS1 recruited DDX3X to stabilize the mRNA level of exosomal protein Rab27a. Moreover, PRR34-AS1 facilitated the malignant phenotypes of THLE-3 cells by elevating Rab27a expression to promote the exosome secretion of VEGF and TGF-β in HCC cells.

Conclusions: The current study revealed a novel function of PRR34-AS1 in accelerating exosome secretion in HCC cells and offered an insight into lncRNA function in the regulation of tumor cell biology.

Keywords: Exosome; Hepatocellular carcinoma; PRR34-AS1; Rab27a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Exosomes* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / pathology
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Messenger / genetics
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Transforming Growth Factor beta
  • RNA, Messenger
  • RNA, Long Noncoding
  • MicroRNAs
  • DDX3X protein, human
  • DEAD-box RNA Helicases
  • RAB27A protein, human