Long non-coding RNA DPP10-AS1 exerts anti-tumor effects on colon cancer via the upregulation of ADCY1 by regulating microRNA-127-3p

Aging (Albany NY). 2021 Mar 19;13(7):9748-9765. doi: 10.18632/aging.202729. Epub 2021 Mar 19.

Abstract

Herein we hypothesized that DPP10-AS1 could affect the development of colon cancer via the interaction with miR-127-3p and adenylate cyclase 1 (ADCY1). After sorting of CD133 positive cells, sphere formation, colony formation, proliferation, invasion, migration, and apoptosis were detected to explore the involvement of DPP10-AS1 and miR-127-3p in the colon cancer stem cell (CCSC) properties through gain- and loss-of function approaches. Furthermore, tumor xenograft in nude mice was conducted to investigate the effect of DPP10-AS1 and miR-127-3p on tumor growth in vivo. Poorly expressed DPP10-AS1 and ADCY1, while highly expressed miR-127-3p were found in CCSCs. Low expression of DPP10-AS1 was correlated with TNM stage, lymphatic node metastasis, and tumor differentiation. Upregulation of DPP10-AS1 increased ADCY1 protein expression, decreased the protein expression of CCSC-related factors, inhibited sphere formation, colony formation, proliferation, invasion and migration, and accelerated apoptosis of HT-29 and SW480 cells by suppressing the expression of miR-127-3p. Further, the above in vitro findings were also confirmed by in vivo assays. Taken together, this study demonstrates that DPP10-AS1 inhibits CCSC proliferation by regulating miR-127-3p and ADCY1, providing fresh insight into a promising novel treatment strategy for colon cancer.

Keywords: adenylate cyclase 1; cancer stem cells; colon cancer; long non-coding RNA DPP10-AS1; microRNA-127-3p.

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Cell Differentiation
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Databases, Factual
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation*

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Adenylyl Cyclases
  • adenylyl cyclase 1