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MiR-138 is a potent regulator of the heterogenous MYC transcript population in cancers

Ng Desi1,2, Velda Teh1, Qing Yun Tong1

  • 1Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.

Oncogene
|December 23, 2021
PubMed

Insights

Shortening of the MYC 3' untranslated region (UTR) in cancer activates oncogenes. Researchers identified microRNA-138 (miR-138) as a key inhibitor of MYC, suppressing tumor growth in colorectal and liver cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • 3'UTR shortening in cancer can lead to oncogene activation by reducing microRNA repression.
  • MYC, a key oncogene overexpressed in over half of all cancers, can be activated without genetic aberrations.
  • The role of 3'UTR alterations in MYC regulation within cancer remains largely uncharacterized.

Purpose of the Study:

  • To investigate the phenomenon of MYC 3'UTR shortening in colorectal cancer (CRC).
  • To identify and validate microRNAs targeting the MYC coding region.
  • To evaluate the therapeutic potential of miR-138 in inhibiting MYC-driven cancers.

Main Methods:

  • Computational and experimental approaches to identify microRNA targets of MYC.
  • Validation of microRNA-mediated repression of MYC expression.
  • In vitro studies using CRC and hepatocellular carcinoma (HCC) cell lines.
  • In vivo studies involving intravenous administration of miR-138 in mouse models.

Main Results:

  • Demonstrated significant shortening of the MYC 3'UTR in colorectal cancer (CRC) samples.
  • Identified and validated miR-138 as a direct microRNA targeting the MYC coding region.
  • Showed that miR-138 inhibits MYC expression and suppresses tumor growth in CRC and HCC cell lines.
  • Confirmed that intravenous miR-138 administration effectively impedes MYC-driven tumor growth in vivo.

Conclusions:

  • The MYC 3'UTR is significantly shortened in cancer, contributing to oncogene dysregulation.
  • miR-138 acts as a potent tumor suppressor by inhibiting MYC expression.
  • miR-138 represents a promising therapeutic agent for MYC-driven cancers, including CRC and HCC.

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