Hindering the Synchronization Between miR-486-5p and H19 lncRNA by Hesperetin Halts Breast Cancer Aggressiveness

Ramah M Abdallah1, Aisha M Elkhouly1, Raghda A Soliman1

  • 1Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.

Abstract

Insights

Hesperitin modulates the miR-486-5p/H19/ICAM-1 axis, impacting metastatic breast cancer (mBC) cell aggressiveness. This natural compound offers a potential therapeutic strategy by targeting key regulatory ncRNAs and ICAM-1 in mBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Crosstalk between non-coding RNAs (ncRNAs) is emerging in metastatic breast cancer (mBC), yet remains understudied.
  • The roles of H19 and miR-486-5p in mBC are debated, and ICAM-1 is a known driver of metastasis.
  • Natural compounds' ability to modulate ncRNA circuits is recognized, but hesperitin's effect on mBC-related ncRNAs is unexplored.

Purpose of the Study:

  • To investigate the impact of hesperitin on the miR-486-5p/H19/ICAM-1 axis in metastatic breast cancer.
  • To explore the therapeutic potential of hesperitin in modulating ncRNA interactions and metastatic progression.

Main Methods:

  • Bioinformatic analysis and cell culture (MDA-MB-231, MCF-7) with oligonucleotide transfection or hesperitin treatment.
  • Gene expression analysis via q-RT-PCR, protein assessment using ELISA, and cytotoxicity evaluation (LDH assay).
  • Functional assays including MTT, colony formation, and migration assays to assess mBC cell behavior.

Main Results:

  • Paradoxical expression of miR-486-5p and H19 observed in breast cancer patients.
  • miR-486-5p mimics and H19 siRNAs suppressed ICAM-1 and mBC hallmarks, revealing a novel bi-directional crosstalk.
  • Hesperitin restored miR-486-5p, inhibited H19 lncRNA and ICAM-1, and reduced mBC cell aggressiveness.

Conclusions:

  • The miR-486-5p/H19/ICAM-1 axis represents a critical regulatory pathway in mBC.
  • Hesperitin effectively modulates this axis, targeting interconnected upstream regulators (miR-486-5p and H19) and downstream effectors (ICAM-1).
  • Hesperitin demonstrates selective regression of mBC cell aggressiveness, highlighting its therapeutic potential.

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