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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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General Research Article

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 *

Volume 22, Issue 3, 2022

Published on: 19 April, 2021

Page: [586 - 595] Pages: 10

DOI: 10.2174/1871520621666210419093652

Price: $65

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.

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.

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

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