The Mechanism Of Long Non-coding RNA HOTAIR Involved In Breast Cancer Cell Radioresistance

Background:Radioresistance remains a therapeutic challenge in progress of breast cancer radiotherapythe main regimen for inoperable and locally advanced breast cancer.Long non-coding RNA HOTAIR(HOX transcript antisense RNA)recently emerged as a carcinogenic promoter and therapeutic targets by inhibiting HOTAIR expression in various cancers including breast cancer.Aim:This study is focused to investigate the radioresistance effects of long non-coding RNA HOTAIR on breast cancer and explore the possible underlying mechanisms.Methods:plasmid pLVX-CMV-PGK-puro was transfected into cell line SKBR3 using liposome,thus overexpressing HOTAIR gene in the cells.Furthermore,radionsensitivity of each cell lines were assessed following overexpressing HOTAIR gene by cell proliferation/viability tests by means of CCK8,transwell,flow cytometry and colony formation assay in vitro,and tumor formation assay in a nude mouse model treated with a single fraction of 8 Gy irradiation in vivo.Following,HOXD10 of the radiated nude mouse was detected by Western blotting.Results:In vivo,mice bearing null vector SKBR3(Vecotr-SKBR3)tumor and stable over-expressing HOTAIR-transfected SKBR3(HOTAIRSKBR3)tumor indicated distinct difference in tumor volume and doubling time in radiation-treated groups(P<0.05).Furthermore,the overexpressed HOTAIR inhibited response of SKBR3 xenografts to irradiation with enhancement factor of 0.31 calculated by dividing the normalized tumor growth delay.In vitro,HOTAIR also efficiently enhanced the radioresistance of breast cancer cells,thus increasing cell proliferation via protein HOXD10.Conclusions:These findings demonstrated that HOTAIR might serve as a valid therapeutic target for the reversal of resistance to radiotherapy in breast cancer.