LncRNA-H19 activates CDC42/PAK1 pathway to promote cell proliferation, migration and invasion by targeting miR-15b in hepatocellular carcinoma

Genomics. 2019 Dec;111(6):1862-1872. doi: 10.1016/j.ygeno.2018.12.009. Epub 2018 Dec 10.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death. This study aims to explore the role and underlying mechanism of H19 in HCC.

Methods: qRT-PCR detected miR-15b-5p and H19 expression, as well as the mRNA level of EMT-associated genes. Western blotting detected protein level of EMT-associated genes. Immunohistochemistry (IHC) examined CDC42 in HCC tissues. Dual luciferase reporter assay verified the regulatory mechanism among H19, miR-15b and CDC42. Colony formation, wound healing assay, transwell, flow cytometry measured proliferation, migration, invasion and apoptosis, respectively.

Results: H19 and CDC42 were up-regulated while miR-15b was down-regulated in HCC cells and tissues. miR-15b interacted with H19 and CDC42 3'-UTR. H19 knockdown inhibited proliferation, migration and invasion, and increased apoptosis, which was rescued by miR-15b inhibitor. H19 knockdown suppressed CDC42/PAK1 pathway and EMT progress.

Conclusion: H19 knockdown inhibited proliferation, migration and invasion, and promoted apoptosis of HCC cells via targeting miR-15b/CDC42/PAK1 axis.

Keywords: CDC42/PAK1 pathway; EMT; Hepatocellular carcinoma; lncRNA-H19; miR-15b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Female
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Neoplasm* / genetics
  • RNA, Neoplasm* / metabolism
  • cdc42 GTP-Binding Protein* / genetics
  • cdc42 GTP-Binding Protein* / metabolism
  • p21-Activated Kinases* / genetics
  • p21-Activated Kinases* / metabolism

Substances

  • H19 long non-coding RNA
  • MIRN15 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • PAK1 protein, human
  • p21-Activated Kinases
  • CDC42 protein, human
  • cdc42 GTP-Binding Protein