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Updated: Jun 24, 2025

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DLK1-DIO3 region as a source of tumor suppressor miRNAs in papillary thyroid carcinoma

Letícia Ferreira Alves1, Leonardo Augusto Marson1, Micheli Severo Sielski1

  • 1Department of Structural and Functional Biology, Institute of Biology, Universidade Estadual de Campinas, Brazil.

Translational Oncology
|June 1, 2024
PubMed
Abstract

Insights

A specific set of 12 microRNAs (miRNAs) from the DLK1-DIO3 region significantly impacts papillary thyroid carcinoma (PTC) progression. Restoring one miRNA, miR-485-5p, inhibited PTC cell proliferation and migration.

Area of Science:

  • Genomics
  • Molecular Biology
  • Cancer Research

Background:

  • Previous studies identified downregulated microRNAs (miRNAs) from the DLK1-DIO3 genomic region in papillary thyroid carcinoma (PTC).
  • The specific roles of individual miRNAs within this large cluster in PTC development were previously unclear.

Purpose of the Study:

  • To elucidate the contribution of DLK1-DIO3-derived miRNAs to papillary thyroid carcinoma.
  • To identify key miRNAs and their targeted pathways involved in PTC pathogenesis.

Main Methods:

  • Utilized computational approaches and in vitro models to analyze miRNA functions.
  • Assessed biological processes and signaling pathways modulated by DLK1-DIO3 miRNAs.
  • Validated targets and functional effects of specific miRNAs in PTC cell lines.

Main Results:

  • Identified a subset of 12 mature miRNAs from the DLK1-DIO3 region responsible for most of the impact on PTC development and progression.
  • These miRNAs collectively modulate critical cancer processes including cell migration, extracellular matrix remodeling, and signal transduction.
  • Restoration of miR-485-5p expression in a BRAFT199A-positive PTC cell line suppressed proliferation and migration by downregulating GAB2 and RAC1.

Conclusions:

  • The DLK1-DIO3 genomic region contains tumor suppressor miRNAs relevant to thyroid cancer.
  • These findings highlight the potential of DLK1-DIO3-derived miRNAs as therapeutic targets for papillary thyroid carcinoma.
Keywords:
DLK1-DIO3 regionMicroRNAPapillary thyroid cancermiR-485–5p

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