Integrative Expression, Survival Analysis and Cellular miR-2909 Molecular Interplay in MRN Complex Check Point Sensor

Jitender Singh1, Namrata Sangwan1, Arushi Chauhan1

  • 1Department of Biophysics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, 160012.

Clinical Breast Cancer
|October 11, 2022
PubMed
Abstract

Insights

MicroRNA-2909 (miR-2909) shows a potential role in breast cancer by forming stable complexes with DNA repair genes MRE11 and RAD50. This interaction, involving argonaute protein, suggests miR-2909 as a molecular marker for breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Breast cancer is a significant global health concern.
  • MicroRNAs (miRNAs) are increasingly recognized for their role in DNA repair gene variants, including MRE11, RAD50, and NBN (collectively MRN-CSG).
  • The specific interactions between MRN-CSG mutations and miRNAs, particularly miR-2909, in breast cancer remain largely unexplored.

Purpose of the Study:

  • To investigate the role of miR-2909 as a molecular mechanistic marker in breast cancer.
  • To analyze genomic and proteomic data of MRN-CSG in breast cancer patients to identify mutation types and their association with survival rates.
  • To perform molecular, 3D-structural, and functional analyses to elucidate miR-2909's regulatory role in MRN-CSG.

Main Methods:

  • Genomic and proteomic data analysis of MRN-CSG in 8426 breast cancer patients.
  • Kaplan-Meier survival curve analysis to correlate mutations with survival rates.
  • Network analysis, disease association studies, molecular hybridization, and argonaute protein docking to assess miR-2909 interactions with MRN-CSG.

Main Results:

  • Genetic alterations in MRN-CSG were identified, predominantly missense mutations, with MRE11 showing higher mRNA expression in invasive ductal breast carcinoma.
  • Patients with unaltered MRN-CSG groups exhibited higher survival rates compared to altered groups.
  • miR-2909 demonstrated strong interactions with MRN-CSG, forming thermodynamically stable hybridized complexes with MRE11 and RAD50 mRNAs, and exhibiting strong binding affinity with argonaute protein.

Conclusions:

  • miR-2909 plays a significant molecular mechanistic role in breast cancer.
  • The formation of stable molecular complexes between miR-2909 and MRE11/RAD50 mRNAs, along with argonaute protein interaction, highlights its potential as a biomarker.
  • Further research into miR-2909's function could lead to novel therapeutic strategies for breast cancer.

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