Long non-coding RNA ABHD11-AS1 promotes colorectal cancer progression and invasion through targeting the integrin subunit alpha 5/focal adhesion kinase/phosphoinositide 3 kinase/Akt signaling pathway

Aging (Albany NY). 2021 Aug 10;13(16):20179-20191. doi: 10.18632/aging.203342. Epub 2021 Aug 10.

Abstract

Long non-coding (lnc)RNA ABHD11-AS1 participates in the development and progress of various cancers, but its role in colorectal cancer (CRC) remains poorly known. In the present study, public database analysis and quantitative reverse transcription PCR of CRC and normal tissues showed that ABHD11-AS1 was overexpressed in CRC and associated with poor prognosis in CRC patients. Both in vitro and in vivo experiments demonstrated that loss-of-function of ABHD11-AS1 attenuated the proliferation, migration, and invasion of CRC cells and induced their apoptosis. Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the phosphoinositide 3 kinase (PI3K)/Akt signaling pathway is a potential target of ABHD11-AS1. Additionally, we noted that ABHD11-AS1 deficiency reduced integrin subunit alpha (ITGA)5 expression, and impaired the phosphorylation of P85, focal adhesion kinase (FAK), and Akt1 in CRC cell lines and tumor tissues of nude mice. Furthermore, we observed that ITGA5 overexpression abrogated the effect of ABHD11-AS1 knockdown on the proliferation and invasion abilities of CRC cells. Taken together, our studies suggest that lncRNA ABHD11-AS1 promotes proliferation, migration, and invasion in CRC by activating the ITGA5/Fak/PI3K/Akt signaling pathway, and that the ITGA5/Fak/PI3K/Akt axis is a promising target for CRC therapy.

Keywords: PI3K/Akt pathway; colorectal cancer; lncRNA-ABHD11-AS1; oncogene profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / physiopathology
  • Disease Progression
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrins / genetics
  • Integrins / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Serine Proteases / genetics
  • Serine Proteases / metabolism*
  • Signal Transduction

Substances

  • ITGA5 protein, human
  • Integrins
  • RNA, Antisense
  • RNA, Long Noncoding
  • Phosphatidylinositol 3-Kinase
  • Focal Adhesion Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • ABHD11 protein, human
  • Serine Proteases