A-to-I miR-378a-3p editing can prevent melanoma progression via regulation of PARVA expression

Guermarie Velazquez-Torres1, Einav Shoshan1, Cristina Ivan2

  • 1Department of Cancer Biology, Unit 1906, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

Nature Communications
|February 2, 2018
PubMed

Insights

RNA editing, specifically A-to-I editing of microRNA (miRNA) miR-378a-3p, is crucial for preventing melanoma metastasis. Edited miR-378a-3p inhibits the PARVA oncogene, halting cancer progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • RNA Biology

Background:

  • Metastatic melanoma exhibits reduced ADAR1 expression, impairing microRNA (miRNA) A-to-I editing.
  • The specific impact of miRNA editing on melanoma progression and metastasis remains largely unknown.

Purpose of the Study:

  • To investigate the role and mechanism of microRNA editing in melanoma metastasis.
  • To determine the function of edited miR-378a-3p in melanoma progression.

Main Methods:

  • Analysis of A-to-I editing status of miR-378a-3p in metastatic and non-metastatic melanoma cells.
  • In vivo metastasis assays using edited and wild-type miR-378a-3p.
  • Assessment of PARVA oncogene expression following miR-378a-3p editing.

Main Results:

  • miR-378a-3p undergoes A-to-I editing exclusively in non-metastatic melanoma cells.
  • Edited miR-378a-3p targets the 3'-UTR of the PARVA oncogene, suppressing its expression.
  • Edited miR-378a-3p effectively inhibits melanoma metastasis in vivo, unlike its wild-type form.

Conclusions:

  • RNA editing of miR-378a-3p plays a critical role in suppressing melanoma metastasis.
  • The edited form of miR-378a-3p acts as a tumor suppressor by inhibiting the PARVA oncogene.

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