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

Abstract

Background: Cancer-associated fibroblasts (CAFs) play an important role in the initiation and progression 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, respectively. 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. Subsequently, 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.