Effects of HOX transcription antisense RNA on carcinogenesis and development of triple-negative breast cancer

Objective To investigate the significance of HOX transcription antisense RNA (HOTAIR) expression in triple-negative breast cancer (TNBC) and explore the molecular modulation of HOTAIR on the progression of TNBC. Methods Sixty-four human TNBC tissues and their corresponding non-tumor tissues were collected, and the HOTAIR levels were detected by real-time quantitative polymerase chain reaction (Real-time PCR). The different HOTAIR levels in tumor and non-tumor tissues were compared. And then we analyzed its significance in TNBC with different pathological stages. In MDA-MB231 cells, the effects of down-regulation of HOTAIR by small interfering RNA (siRNA) on the proliferation (MTT) and apoptosis (Western blotting) were detected. The effects of down-regulation of HOTAIR on the expression of enhancer of zeste homolog2 (EZH2), the enzymatic subunit of ploycomb repressor complex (PRC2), were detected. SPSS19.0 statistical software was used for analysis. Results Compared with the non-tumor tissues, the HOTAIR expression was significantly increased in TNBC tumors (0.71±0.10 vs. 0.50±0.06, t=20.286, P<0.01), especially in TNBC with advanced stage (0.78±0.05 vs. 0.64±0.07, t=8.625, P<0.01). In TNBC cells, treatment of siEZH2 showed similar effects on the cell proliferation and apoptosis. In TNBC cells, EZH2 expression was down-regulated by siHOTAIR. However, HOTAIR expression had no significant change after siEZH2 treatment. Conclusion HOTAIR is highly expressed in TNBC and associated with poor prognosis. Our results suggest HOTAIR may induce the carcinogenesis in TNBC probably through regulating EZH2. Key words: Triple negative breast cancer; HOX transcription antisense RNA; Enhancer of zeste homolog 2