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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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ROCK1-PredictedmicroRNAs Dysregulation Contributes to Tumor Progression in Ewing Sarcoma.

G M Roberto1, L E A Delsin2, G M Vieira2

  • 1Regional Blood Center, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil.

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|December 23, 2017
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Summary

Rho-associated kinases and microRNAs are key in tumor invasion. In Ewing Sarcoma (EWS), down-regulated miR-124-3p, miR-139-5p, and miR-584-5p correlate with disease progression and reduced survival, suggesting biomarker potential.

Keywords:
Ewing sarcomaInvasionMotilityRockmicroRNA

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis Research

Background:

  • Rho-associated kinases (ROCK) and specific microRNAs (miRNAs) are implicated in tumor invasion.
  • The precise role of these molecules in Ewing Sarcoma (EWS) metastasis remains incompletely understood.

Purpose of the Study:

  • To investigate the expression profiles of ROCK1/ROCK2 and metastasis-associated miRNAs (miR-124-3p, miR-138-5p, miR-139-5p, miR-335-5p, miR-584-5p) in EWS.
  • To correlate their expression with clinical parameters and evaluate their functional impact on EWS cell invasion and migration in vitro.

Main Methods:

  • Quantitative reverse transcription PCR (qRT-PCR) for gene and miRNA expression analysis.
  • Correlation analysis with clinical parameters in EWS tissues.
  • In vitro functional assays (colony formation, invasion, migration) using SK-ES-1 cells transfected with miRNA mimics.

Main Results:

  • ROCK1 expression was reduced in EWS tissues, but not significantly associated with pathological parameters.
  • miR-124-3p, miR-139-5p, and miR-335-3p were significantly downregulated and positively correlated with ROCK1 expression.
  • Lower levels of miR-139-5p and miR-584-5p correlated with disease progression, while reduced miR-139-5p and miR-124-3p expression were linked to poorer survival.

Conclusions:

  • Downregulation of miR-124-3p, miR-139-5p, and miR-584-5p is associated with disease progression in Ewing Sarcoma.
  • These miRNAs may serve as potential biomarkers for risk assessment in EWS patients.
  • The exact functional role of specific miRNAs, such as miR-139-5p, requires further elucidation for targeted therapeutic strategies.