Hindering the Synchronization Between miR-486-5p and H19 lncRNA by Hesperetin Halts Breast Cancer Aggressiveness Through Tuning ICAM-1

Author(s):

Ramah M. Abdallah , Aisha M. Elkhouly , Raghda A. Soliman , Nehad El Mechawy, Ahmed El Sebaei , Amira A. Motaal , Hesham El-Askary , Rana A. Youness * and Reem A. Assal *   Pages 586 - 595 ( 10 )

Abstract:

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. <p> Objective: The aim of this study is to investigate the impact of hesperitin on miR-486-5p/H19/ICAM-1 axis. <p> 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. <p> 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. <p> 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.

Keywords:

miR-486-5p, H19, hesperitin, ICAM-1, breast cancer, metastasis.

Affiliation:

Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Surgical Oncology and Endocrinology Department, Cairo, Pathology Department International Medical center, Cairo, Department of Pharmacognosy, Cairo University, Cairo, Department of Pharmacognosy, Cairo University, Cairo, Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo

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