Long noncoding RNA CASC21 exerts an oncogenic role in colorectal cancer through regulating miR-7-5p/YAP1 axis

Biomed Pharmacother. 2020 Jan:121:109628. doi: 10.1016/j.biopha.2019.109628. Epub 2019 Nov 12.

Abstract

Background: Emerging evidences show that long non-coding RNAs (lncRNAs) are widely involved in various cell processes and tumor progression. The aim of this study was to investigate the role of new lncRNA homo sapiens cancer susceptibility 21 (CASC21) in the cancer biology of colorectal cancer and explore the underlying mechanism.

Methods: We silenced the expression of CASC21 using siRNA interference in colorectal cancer cell lines HT29 and SW480, and the effects of CASC21 knockdown on cell proliferation, migration, invasion and apoptosis were assessed using CCK8, colony formation, wound-healing, Transwell and flow cytometry assays. Dual-luciferase reporter assay was performed to determine the relationship among CASC21, miR-7-5p and YAP1. Western blot analysis was used to examine expression of related proteins.

Results: By bioinformatics analysis, CASC21 was found to be significantly up-regulated in colorectal cancer tissues. Moreover, CASC21 knockdown displayed significant depression in cell viability, proliferation, migration, and invasion in colorectal cancer cells, as well as EMT process, while cell apoptosis was promoted by regulating the Bcl-2/Bax axis and Caspase cascade. Mechanistically, CASC21 could competently bind to miR-7-5p, resulting in increased YAP1 expression. Furthermore, up-regulation of YAP1 could rescue the inhibitory effects of CASC21 knockdown on EMT and cell invasion.

Conclusion: Collectively, these results suggest that CASC21 functions as a ceRNA that plays an oncogenic role in the progression of colorectal cancer by regulating the miR-7-5p/YAP1 axis. LncRNA CASC21 might be a potential target for therapy of colorectal cancer.

Keywords: Colorectal cancer; YAP1; ceRNA; lncRNA CASC21; miR-7-5p.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology*
  • Apoptosis
  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN7 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human