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MicroRNA-33a-5p suppresses colorectal cancer cell growth by inhibiting MTHFD2

Yan Yan1,2, Ding Zhang3, Ting Lei4

  • 1Institute of Cancer Research, School of Basic Medical Science of Xi'an Jiaotong University, Xi'an, China.

Clinical and Experimental Pharmacology & Physiology
|June 19, 2019
PubMed

Insights

MicroRNA-33a-5p (miR-33a-5p) suppresses colorectal cancer (CRC) growth and migration by targeting MTHFD2. This study reveals miR-33a-5p

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Colorectal cancer (CRC) is a prevalent malignancy with poorly understood internal mechanisms.
  • MicroRNAs (miRs) are implicated in CRC development, with abnormal miR-33a-5p expression noted.
  • The specific function and downstream targets of miR-33a-5p in CRC remain unclear.

Purpose of the Study:

  • To elucidate the function and downstream mechanism of miR-33a-5p in colorectal cancer.
  • To investigate the role of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) as a target of miR-33a-5p.

Main Methods:

  • Quantitative analysis of miR-33a-5p expression in CRC tissues and cell lines.
  • In vitro studies involving miR-33a-5p overexpression in HCT116 and HT29 cells to assess proliferation, clone formation, cell cycle, and migration.
  • In vivo tumor formation assays in nude mice.
  • Bioinformatics predictions and luciferase reporter assays to confirm MTHFD2 as a direct target of miR-33a-5p.
  • MTHFD2 overexpression studies to evaluate its impact on CRC cell proliferation and migration.

Main Results:

  • miR-33a-5p was significantly downregulated in CRC tissues and cell lines.
  • Overexpression of miR-33a-5p suppressed CRC cell proliferation, clone formation, G1/S progression, and migration in vitro.
  • In vivo, miR-33a-5p overexpression significantly inhibited tumor formation and Ki67 expression.
  • MTHFD2 protein expression was elevated in CRC tissues.
  • MTHFD2 was confirmed as a direct target of miR-33a-5p.
  • MTHFD2 overexpression promoted CRC cell proliferation and migration, validating it as a functional target.

Conclusions:

  • miR-33a-5p acts as a tumor suppressor in colorectal cancer.
  • The inhibitory effect of miR-33a-5p on CRC growth and migration is mediated through the targeting of MTHFD2.
  • This study identifies a novel regulatory pathway involving miR-33a-5p and MTHFD2 in CRC pathogenesis.
Keywords:
colorectal cancermethylenetetrahydrofolate dehydrogenase 2microRNA-33a-5pmigrationproliferation

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