The Role Of Long Non-coding RNA HOTAIR In The Progression Of Cervical Cancer And Its Mechanism

Objective To evaluate the role of the long non-coding RNA(lncRNA)HOTAIR in cervical cancer pathogenesis and its mechanisms.Methods The subjects were 51 patients with cervical cancer who underwent surgery in our hospital from January 2013 to December 2014.20 cases of hysteromyoma treated by simple hysterectomy were used as control group.Real time fluorescence quantitative PCR was used to detect the expression level of HOTAIR RNA in cervical cancer and control subjects.SPSS20.0 statistical software was used for statistical analysis.Chi-square test,t-test and Fisher exact test were used to evaluate the correlation between HOTAIR expression and clinicopathological parameters,such as age,tumor size,histological grade,FIGO stage and lymph node metastasis.Kaplan-Meier method was used to analyze the total survival time and Cox proportional risk model was used to evaluate the predictive value of different factors.At the level of SiHa cells,the effects of overexpression or inhibition of HOTAIR on cell proliferation,invasion and apoptosis were observed.Results Compared with the control group,the serum HOTAIR RNA level in cervical cancer patients was significantly higher(0.79±0.24 vs.4.21±0.89),P< 0.001).In order to indicate the correlation between circulating HOTAIR and clinical pathological characteristics of cervical cancer.We detected serum HOTAIR levels in 51 cases of cervical cancer at different times.The mean HOTAIR concentrations in phase I and II were 4.35±1.02 and 3.82±0.91 respectively,and the difference was not statistically significant.However,high expression of HOTAIR was associated with FIGO staging(P=0.045),tumor size(P=0.038),lymphatic interstitial infiltration(P=0.034)and lymph node metastasis(P=0.047).Next,we examined the relationship between HOTAIR expression and outcome.The patients were followed up for 50 months.Univariate analysis showed that lymphatic interstitial infiltration(HR=6.355,P=0.013)and high HOTAIR expression(HR=4.269,P=0.038)were prognostic factors for disease-free survival.Kaplan Meier diagram showed that the overall survival time of patients with stage II cervical cancer with high expression of HOTAIR was significantly shortened(P=0.034 and 0.032).Cox proportional hazard model showed that lymphatic space invasion(HR = 2.373,P = 0.027)was an independent prognostic factor for disease-free survival.After SiHa cells overexpressed HOTAIR,the level of HOTAIR RNA in SiHacells increased significantly.Overexpression of HOTAIR significantly increased SiHa cell colony formation and cell invasion.At the same time,overexpression of HOTAIR also promoted the growth and migration of SiHa cells.Conclusion The study revealed increased serum HOTAIR levels in patients with cervical cancer.Higher serum HOTAIR expression was associated with the clinicopathological features and prognosis of cervical cancer patients.Determination of HOTAIR expression may be helpful in assessing the clinical pathology staging and/or prognosis of patients with cervical cancer.HOTAIR may be a potential therapeutic target for cervical cancer.