MYC-Induced Upregulation of Lncrna ELFN1-AS1 Contributes to Tumor Growth in Colorectal Cancer via Epigenetically Silencing TPM1

Mol Cancer Res. 2022 Nov 3;20(11):1697-1708. doi: 10.1158/1541-7786.MCR-22-0009.

Abstract

Recently, long noncoding RNAs (lncRNA) have been reported as tumor suppressors or oncogenes in colorectal cancer. This study aims to discover functional role of a novel lncRNA in colorectal cancer tumorigenesis. Expression profile of fibronectin type III domain containing 1 antisense RNA 1 (ELFN1-AS1) in colorectal cancer samples was displayed on TCGA database. Expression level of ELFN1-AS1 was tested in colorectal cancer tissues and cell lines via qRT-PCR. Functional role of ELFN1-AS1 was assessed by loss-of-function assays. Mechanism experiments, such as chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay, were done to analyze the molecular mechanism of ELFN1-AS1 in colorectal cancer. ELFN1-AS1 knockdown inhibited colorectal cancer tumor growth through restricting cell proliferation and facilitating cell apoptosis. ELFN1-AS1 was transcriptionally activated by MYC. Moreover, ELFN1-AS1 led to transcriptional silencing of tropomyosin 1 (TPM1) via recruiting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and forkhead box P1 (FOXP1). Collectively, MYC-upregulated ELFN1-AS1 recruited EZH2 and FOXP1 to restrain TPM1 expression, thereby promoting colorectal cancer tumor growth.

Implications: This study revealed a novel molecular pathway in colorectal cancer progression, which may provide new method for early diagnosis and treatment of colorectal cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Repressor Proteins / genetics
  • Tropomyosin / genetics
  • Tropomyosin / metabolism
  • Up-Regulation

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • TPM1 protein, human
  • Tropomyosin
  • FOXP1 protein, human
  • Repressor Proteins
  • Forkhead Transcription Factors