Down-Regulation of MicroRNA-214 Contributed to the Enhanced Mitochondrial Transcription Factor A and Inhibited Proliferation of Colorectal Cancer Cells

Cell Physiol Biochem. 2018;49(2):545-554. doi: 10.1159/000492992. Epub 2018 Aug 29.

Abstract

Background/aims: Colon cancer, also known as colorectal cancer (CRC), is one of the most common malignant tumors globally. Although significant advances have been made for developing novel therapeutics, the mechanisms of progression of colorectal cancer are still poorly understood.

Methods: In this study, we identified down-regulation of microRNA-214 (miR-214) as the contributing factor for CRC. Mitochondrial transcription factor A (TFAM) and miR-214 expression in tumor samples from colorectal cancer patients and cancer cell lines were examined by reverse transcription and real-Time PCR (qPCR) or Western Blotting.

Results: Our data demonstrated that miR-214 was significantly down-regulated in the tissue samples from CRC patients as well as CRC derived cell lines. TFAM overexpression was also observed in CRC patients and identified as a target for miR-214. Knockdown of TFAM by miR-214 mimics significantly inhibited the proliferation of CRC cell lines. Also, down-regulation of TFAM inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation and the expression of NF-κB depended genes.

Conclusion: In conclusion, our data suggested that down-regulation of MiR-214 contributed to the enhanced TFAM expression and decreased proliferation of CRC cells.

Keywords: Colorectal cancer; NF-κB; Proliferation; TFAM; miR-214.

MeSH terms

  • 3' Untranslated Regions
  • Antagomirs / metabolism
  • Base Sequence
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • NF-kappa B / metabolism
  • Sequence Alignment
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • X-Linked Inhibitor of Apoptosis Protein / metabolism
  • bcl-X Protein / metabolism

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • DNA-Binding Proteins
  • MIRN214 microRNA, human
  • MicroRNAs
  • Mitochondrial Proteins
  • NF-kappa B
  • Transcription Factors
  • X-Linked Inhibitor of Apoptosis Protein
  • bcl-X Protein
  • mitochondrial transcription factor A