Circ_0000317/microRNA-520g/HOXD10 axis affects the biological characteristics of colorectal cancer

Kaohsiung J Med Sci. 2021 Nov;37(11):951-963. doi: 10.1002/kjm2.12422. Epub 2021 Jul 22.

Abstract

Circular RNAs (circRNAs) are a class of noncoding RNAs that are widely expressed in cancer tissues and play a pro- or anticancer role in modulating cancer progression. This work is aimed to probe the biological role of circ_0000317 in colorectal cancer (CRC) and its underlying mechanism. Circ_0000317 was selected from the circRNA microarray datasets (GSE121895). Quantitative real-time polymerase chain reaction was utilized to examine circ_0000317, microRNA (miR)-520g, and homeobox D10 (HOXD10) mRNA expression in CRC. Cell Counting Kit-8 and Transwell experiments were conducted to examine the effects of circ_0000317 on proliferation, migration, and invasion of CRC cells. Bioinformatic analysis and dual-luciferase reporter gene experiments were implemented to predict and validate the targeting relationship between circ_0000317 and miR-520g, miR-520g, and HOXD10. Western blot was employed to examine HOXD10 expression at protein level in CRC cells. Circ_0000317 and HOXD10 mRNA expression were unveiled to be down-modulated and miR-520g expression was up-modulated in CRC. Functionally, circ_0000317 overexpression repressed CRC cell proliferation, migration, and invasion. Mechanistically, miR-520g was a direct target of circ_0000317 and miR-520g specifically modulated HOXD10 expression. Furthermore, miR-520g mimics partially counteracted the suppressing effect of circ_0000317 on malignant phenotype of CRC cells. Circ_0000317 represses CRC progression by targeting miR-520g and modulating HOXD10 expression. Hence, circ_0000317 may be a promising diagnostic biomarker and a therapeutic target for CRC.

Keywords: CRC; HOXD10; circ_0000317; miR-520g.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Base Pairing
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Computational Biology / methods
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • HT29 Cells
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Homeodomain Proteins
  • MIRN520 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Transcription Factors
  • HOXD10 protein, human
  • Luciferases