ZNF148 modulates TOP2A expression and cell proliferation via ceRNA regulatory mechanism in colorectal cancer

Xian Hua Gao1, Juan Li, Yan Liu

  • 1Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University Department of Nephrology, Changhai Hospital, Second Military Medical University Department of Epidemiology, Second Military Medical University, Shanghai, China.

Medicine
|January 11, 2017
PubMed
Abstract

Insights

Zinc finger protein 148 (ZNF148) and TOP2A RNA molecules regulate each other via competing endogenous RNA (ceRNA) mechanisms in colorectal cancer (CRC). This interaction impacts cell proliferation, offering new insights into CRC development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Competing endogenous RNA (ceRNA) regulation is a novel mechanism where RNA molecules share target microRNAs (miRNAs).
  • This interaction allows RNA molecules to compete for binding to the same miRNA pool, influencing gene expression.

Purpose of the Study:

  • To investigate the competing endogenous RNA (ceRNA) regulatory mechanism between Zinc finger protein 148 (ZNF148) and TOP2A in colorectal cancer (CRC).
  • To determine the impact of this ceRNA interaction on CRC cell proliferation.

Main Methods:

  • Analyzed ZNF148 and TOP2A expression in 742 CRC tissues using immunohistochemistry (IHC).
  • Quantified mRNA and miRNA expression in 53 CRC tissues via reverse transcription polymerase chain reaction.
  • Employed bioinformatics, correlation analysis, RNA interference, gene overexpression, and luciferase assays to elucidate ceRNA mechanisms.

Main Results:

  • ZNF148 and TOP2A protein and mRNA levels showed positive correlations in CRC tissues.
  • Bioinformatics identified 13 common target miRNAs for ZNF148 and TOP2A, including miR101, miR144, miR335, and miR365.
  • ZNF148 and TOP2A were found to regulate each other through a ceRNA mechanism involving their 3'UTRs, impacting CRC cell proliferation.

Conclusions:

  • ZNF148 and TOP2A engage in a mutual ceRNA regulatory mechanism within colorectal cancer.
  • This interaction significantly influences colorectal cancer cell proliferation, highlighting a novel regulatory pathway in CRC development.

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