Delivery of LINC00589 via mesoporous silica nanoparticles inhibits peritoneal metastasis in gastric cancer

Cancer Lett. 2022 Nov 28:549:215916. doi: 10.1016/j.canlet.2022.215916. Epub 2022 Sep 17.

Abstract

Peritoneal metastasis is one of the common forms of metastasis in gastric cancer (GC). In this study, we identified the expression pattern of LINC00589 in GC patients and investigate the biological function in GC cells. RNA-pulldown assay was performed to explore the underlying molecular mechanism. Further, we utilize polyethyleneimine-modified mesoporous silica nanoparticles (PMSNs) as the nanocarriers for delivery of LINC00589 encoding plasmid and tested its therapeutic potential for GC with peritoneal dissemination. We revealed that LINC00589 was downregulated in GC tissues and suppressed the metastatic ability of GC cells. Mechanistically, LINC00589 exerted tumor suppressive function by promoting hnRNPA1 protein ubiquitination and proteasomal degradation, thus blocking alternative splicing of PKM to PKM2. Furthermore, LINC00589 delivered by PMSNs could suppress the peritoneal metastasis of GC in vivo and in vitro. This work may provide a new treatment option in GC peritoneal metastasis.

Keywords: Gastric cancer; Mesoporous silica nanoparticles; Peritoneal metastasis; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nanoparticles*
  • Peritoneal Neoplasms* / drug therapy
  • Peritoneal Neoplasms* / genetics
  • Peritoneal Neoplasms* / pathology
  • Polyethyleneimine
  • RNA
  • Silicon Dioxide / metabolism
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism

Substances

  • RNA
  • Silicon Dioxide
  • Polyethyleneimine