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The Modulatory Role of MicroRNA-873 in the Progression of KRAS-Driven Cancers

Hamada A Mokhlis1, Recep Bayraktar2, Nashwa N Kabil2

  • 1Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, The University of Al-Azhar, Cairo, Egypt.

Molecular Therapy. Nucleic Acids
|January 18, 2019
PubMed

Insights

MicroRNA-873 (miR-873) suppresses tumor growth by targeting KRAS in pancreatic and breast cancers. Restoring miR-873 inhibits cancer progression and may offer a novel gene therapy approach.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Therapy

Background:

  • KRAS mutations are common in pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC).
  • MicroRNAs (miRNAs) play crucial roles in cancer development and therapy.
  • miR-873 was identified as a potential regulator of KRAS.

Purpose of the Study:

  • To investigate the role of miR-873 in PDAC and TNBC.
  • To determine if miR-873 targets KRAS and affects cancer progression.
  • To evaluate miR-873 as a potential therapeutic agent.

Main Methods:

  • In silico prediction algorithms to identify miR-873 as a KRAS regulator.
  • Analysis of miR-873 expression in cancer cell lines and patient samples.
  • In vitro experiments demonstrating miR-873 binding to KRAS mRNA and its effects on cancer cell behavior.
  • In vivo studies using nanoparticle delivery of miR-873 in mouse models.

Main Results:

  • Reduced miR-873 expression correlated with shorter survival in PDAC and TNBC patients.
  • miR-873 directly suppressed KRAS expression by binding to its 3' UTR.
  • Restoring miR-873 induced apoptosis, inhibited proliferation and invasion, and suppressed ERK and PI3K/AKT signaling.
  • KRAS overexpression rescued the anti-cancer effects of miR-873.
  • In vivo delivery of miR-873 nanoparticles inhibited tumor growth in PDAC and TNBC models.

Conclusions:

  • miR-873 functions as a tumor suppressor by targeting KRAS in PDAC and TNBC.
  • miR-873-based gene therapy holds promise for treating PDAC and TNBC.
Keywords:
KRASbreast cancergene regulationgene silencinginvasionliposomesmiR-873microRNAnanoparticlesncRNAnon-coding RNAoncogenepancreatic cancerproliferationtherapytriple-negative breast cancertumorigenesis

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