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HMGA2 regulation by miRNAs in cancer: Affecting cancer hallmarks and therapy response

Mehrdad Hashemi1, Mohsen Rashidi2, Kiavash Hushmandi3

  • 1Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Pharmacological Research
|March 17, 2023
PubMed

Insights

High mobility group A 2 (HMGA2) protein drives cancer progression by affecting hallmarks like proliferation and metastasis. Targeting the HMGA2 axis with non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), offers a promising therapeutic strategy for various cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • High mobility group A 2 (HMGA2) protein is aberrantly expressed in cancer, promoting hallmarks like proliferation, invasion, and therapy resistance.
  • HMGA2 influences critical cancer signaling pathways, including Wnt/β-catenin and mTOR.
  • Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), play crucial roles in regulating gene expression and cellular processes.

Purpose of the Study:

  • To review the significance of the miRNA/HMGA2 axis in modulating various cancer types.
  • To discuss the role of lncRNAs and circRNAs as upstream regulators of the miRNA/HMGA2 axis.
  • To explore the impact of miRNA-HMGA2 interactions on cancer cell response to therapy.

Main Methods:

  • Literature review focusing on the molecular mechanisms of HMGA2 and ncRNAs in cancer.
  • Analysis of signaling pathways targeted by HMGA2.
  • Examination of regulatory interactions between miRNAs, lncRNAs, circRNAs, and HMGA2.

Main Results:

  • Aberrant HMGA2 expression is a key driver of cancer progression and is linked to poor patient outcomes.
  • The miRNA/HMGA2 axis is a critical regulator of cancer hallmarks and signaling pathways.
  • lncRNAs and circRNAs act as upstream modulators of this axis, influencing miRNA activity.
  • Interactions within the miRNA/HMGA2 axis significantly affect cancer cell sensitivity to therapeutic interventions.

Conclusions:

  • Targeting the HMGA2 protein and its regulatory axis with ncRNAs presents a promising therapeutic avenue for cancer treatment.
  • Further investigation into the miRNA/HMGA2 axis and its upstream regulators could lead to novel clinical trial strategies.
  • Modulating the miRNA/HMGA2 interaction holds potential for improving patient outcomes across diverse cancer types.
Keywords:
CancerCircRNAsHMGA2LncRNAMiRNA

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