CASC21, a FOXP1 induced long non-coding RNA, promotes colorectal cancer growth by regulating CDK6

Aging (Albany NY). 2020 Jun 25;12(12):12086-12106. doi: 10.18632/aging.103376. Epub 2020 Jun 25.

Abstract

Emerging studies indicate that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). Here, we reported lncRNA CASC21, which is induced by FOXP1, functions as an oncogene in CRC. We systematically elucidated its clinical significance and possible molecular mechanism in CRC. LncRNA expression in CRC was analyzed by RNA-sequencing data in TCGA. The expression level of CASC21 in tissues was determined by qRT-PCR. The functions of CASC21 was investigated by in vitro and in vivo assays (CCK8 assay, colony formation assay, EdU assay, xenograft model, flow cytometry assay, immunohistochemistry (IHC) and Western blot). Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP) and luciferase reporter assays were utilized to demonstrate the potential mechanisms of CASC21. CASC21 is overexpressed in CRC and high CASC21 expression is associated with poor survival. Functional experiments revealed that CASC21 promotes CRC cell growth. Mechanistically, we found that CASC21 expressed predominantly in the cytoplasm. CASC21 could interact with miR-539-5p and regulate its target CDK6. Together, our study elucidated that CASC21 acted as an oncogene in CRC, which might serve as a novel target for CRC diagnosis and therapy.

Keywords: CASC21; CDK6; colorectal cancer; lncRNA; miR-539-5p.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cohort Studies
  • Colectomy
  • Colon / pathology
  • Colon / surgery
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Cyclin-Dependent Kinase 6 / genetics*
  • Datasets as Topic
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oncogenes
  • Prognosis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Seq
  • Repressor Proteins / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • FOXP1 protein, human
  • Forkhead Transcription Factors
  • MIRN539 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Repressor Proteins
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6