Breast Cancer-Associated Fibroblasts Could Induce the PI3K/Akt/ mTOR Signaling Pathway Through Downstream Long Non-Coding RNA HOTAIR

Mona Sadeghalvad; Hamid-Reza  Mohammadi-Motlagh; Kamran Mansouri; Ali Mostafaie; Farshid Noorbakhsh; Sadaf Alipour; Foroozan Ghalkhani; Ramesh Omranipour; Seid-Shahram Miraghaee; Sarah Kiani; Nima Rezaei

doi:10.18502/igj.v8i1.17996

Mona Sadeghalvad Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Hamid-Reza Mohammadi-Motlagh Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Kamran Mansouri Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Ali Mostafaie Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Farshid Noorbakhsh Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Sadaf Alipour Breast Disease Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
Foroozan Ghalkhani Imam Reza Hospital, AJA University of Medical Sciences, Tehran, Iran
Ramesh Omranipour Breast Disease Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
Seid-Shahram Miraghaee Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Sarah Kiani Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Nima Rezaei Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/igj.v8i1.17996

Keywords: Breast Cancer; Tumor-Associated Fibroblasts; HOTAIR; PI3K/Akt/mTOR Pathway; Tumor Microenvironment

Abstract

Background: Cancer-associated fibroblasts (CAFs) play an important role in the initiation and progres- sion of tumor cells. These cells can trigger signaling pathways involved in tumor progression. HOTAIR, an increased long non-coding RNA (lncRNA) in breast cancer, has a vital role in the tumorigenesis and development of breast cancer cells.

Methods: In this study, a fibroblast cell culture medium was used to investigate its possible role in inducing the HOTAIR expression and PI3K/Akt/mTOR pathway in breast cancer cells. CAFs and normal fibroblasts (NFs) were isolated from tumors of 6 patients with breast cancer and subjects with healthy breasts, respec- tively. The MCF-7 cells were cultured in a medium obtained from CAFs (CAF-CM) or NFs (NF-CM), and then the expression of HOTAIR and PI3K/Akt/mTOR in MCF-7 cells was assessed using Real-Time PCR. HOTAIR was silenced in MCF-7 cells using siRNAs and then cultured in CAF-CM or NF-CM. Subse- quently, the phosphorylation status of PI3K/Akt/mTOR proteins was analyzed by western blotting.

Results: Fibroblast culture medium enhanced the expression of HOTAIR and activation of the PI3K/Akt/ mTOR pathway in breast cancer cells. By HOTAIR silencing, reduced activity of the PI3K/Akt/mTOR pathway, as well as the lower effect of fibroblast culture medium in the induction of PI3K/Akt/mTOR pathway, was seen.

Conclusion: HOTAIR can play a role as a mediator in inducing the PI3K/Akt/mTOR pathway in breast cancer cells by the effect of cancer-associated fibroblast cells.