Hindering the Synchronization Between miR-486-5p and H19 lncRNA by Hesperetin Halts Breast Cancer Aggressiveness Through Tuning ICAM-1
| Autor: | Hesham I. El-Askary, Amira Abdel Motaal, Rana Ahmed Youness, R.A. Soliman, R.A. Assal, Ahmed El Sebaei, Ramah M Abdallah, A. Elkhouly, Nahed El Meckawy |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Cancer Research Small interfering RNA Cell Antineoplastic Agents Breast Neoplasms Biology Metastasis chemistry.chemical_compound Gene expression medicine Tumor Cells Cultured Cytotoxic T cell Humans Aged Pharmacology ICAM-1 Hesperidin Hesperetin Transfection Middle Aged medicine.disease Intercellular Adhesion Molecule-1 MicroRNAs medicine.anatomical_structure chemistry Cancer research Molecular Medicine Female RNA Long Noncoding |
| Zdroj: | Anti-cancer agents in medicinal chemistry. 22(3) |
| ISSN: | 1875-5992 |
| Popis: | 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. Methodology: 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|