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Updated: Nov 8, 2025

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
Published on: June 7, 2016
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.
Background:
Recently, a novel crosstalk between non-coding RNAs (ncRNAs) has been casted. However, this has been seldom investigated in metastatic BC (mBC). H19 and miR-486-5p role in mBC are controversial. ICAM-1 is a recently recognized metastatic engine in mBC. Natural compounds were recently found to alter ncRNAs/target circuits. Yet, Hesperitin's modulatory role in altering such circuits has never been investigated in mBC.
Objective:
The aim of this study is to investigate the impact of hesperitin on miR-486-5p/H19/ICAM-1 axis.
Methods:
BC patients (n=20) were recruited in the study. Bioinformatic analysis was performed using different prediction softwares. MDA-MB-231 and MCF-7 cells were cultured and transfected using several oligonucleotides or treated with serial dilutions of hesperitin. RNA was extracted and gene expression analysis was performed using q-RT-PCR. ICAM-1 protein levels were assessed using human ICAM-1 Elisa Kit. Cytotoxic potential of hesperitin against normal cells was assessed by LDH assay. Several functional analysis experiments were performed such as MTT, colony forming and migration assays.
Results:
The study showed that miR-486-5p and H19 had paradoxical expression profiles in BC patients. miR- 486-5p mimics and H19 siRNAs repressed ICAM-1 and halted mBC hallmarks. A novel crosstalk between miR- 486-5p and H19 was observed highlighting a bi-directional relationship between them. Hesperetin restored the expression of miR-486-5p, inhibited H19 lncRNA and ICAM-1 expression and selectively regressed mBC cell aggressiveness.
Conclusion:
miR-486-5p and H19 are inter-connected upstream regulators for ICAM-1 building up miR-486- 5p/H19/ICAM-1 axis that has been successfully tuned in mBC cells by hesperitin.
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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