1.Expression and clinical significance of long non-coding RNA HOTTIP in tissues of patients with endometrial carcinoma
GAO Yuxia1 ; DONG Xuecai1 ; WANG Wenxiang1 ; SI Xiaohui2 ; LI Hongyu3
Chinese Journal of Cancer Biotherapy 2020;27(12):1378-1382
[Abstract] Objective: To investigate the expression and clinical significance of long non-coding RNA (lncRNA) HOTTIP in tissues of patients with endometrial carcinoma. Methods: A total of 109 cases of patients with endometrial carcinoma who underwent surgery in Xingxiang Central Hospital from April 2012 to April 2014 were selected. The endometrial carcinoma tissue and its corresponding adjacent tissue (more than 5 cm from the cancer margin) were obtained. The expressions of HOTTIP in endometrial carcinoma and adjacent tissues were detected by qRT-PCR. All patients were followed up from the first postoperative day. The follow-up deadline was April 30, 2019. The end-point event was death and the patient's survival time was recorded. Results: The relative expression level of HOTTIP in endometrial carcinoma tissues was (2.55±0.21), which was higher than that in the adjacent tissue (1.03±0.16) (t=60.631, P<0.01). The differences of the relative expression levels of HOTTIP in endometrial carcinoma tissues between different FIGO stage, histological grade, depth of myometrial invasion, lymphatic vascular infiltration status and lymph node metastasis were statistically significant (all P<0.05). Kaplan-Meier survival analysis showed that the 5-year survival rate and the survival time in the low expression group were higher than those in the high expression group [78.57% vs 37.04%, (70.67±4.94) months vs (42.14±3.65) months], the difference was statistically significant (χ2=12.839, P<0.01). Cox proportional hazards regression model analysis showed that the FIGO stage [HR=2.248 (95%CI: 1.034-4.887)], myometrial invasion depth [HR=3.055 (95%CI: 1.668-5.592)], lymph node metastasis [HR=3.811 (95%CI: 1.786-8.131)] and the expression of HOTTIP [HR=2.649 (95%CI: 1.026-6.842)] were all independent influence factors for the prognosis of patients with endometrial carcinoma. Conclusion: lncRNA HOTTIP is highly expressed in endometrial carcinoma tissues and associated with malignant progression of patients. It is an independent influencing factor for patients’ prognosis.
2.Inhibitory effect of silencing HMGB1 gene on growth of human epithelial ovarian cancer xenografts in nude mice
WU Meiqin ; WANG Yong ; ZHU Hongfei ; SONG Xiaojie ; LI Yuxia1 ; LIU Zhihui ; ZHAO Shuyan ; YUAN Jing ; GONG Jingjing ; LIANG Xing ; CHEN Dandan ; NING Xiangcheng
Chinese Journal of Cancer Biotherapy 2020;27(6):629-633
[Abstract] Objective: To investigate the effect of HMGB1 gene on the growth of human epithelial ovarian cancer xenografts in nude mice, and to lay a foundation for finding new targets for the treatment of ovarian cancer. Methods: Human epithelial ovarian cancer SKOV3 cells in logarithmic growth phase were selected to establish a human epithelial ovarian cancer xenograft model in nude mice. Nude mice with successful model establishment were randomly divided into control group and HMGB1-siRNA group. On the 7th, 9th, 11th, 14th, and 16th days after cell inoculation, the same amount of saline and HMGB1-siRNA were respectively injected into two groups of mice under the armpit.After 3 weeks, the nude mice were sacrificed by cervical dislocation, the tumor tissues were separated, and the volume of the tumor was measured. The apoptosis of transplanted tumor cells was detected by Tunnel staining. The expressions of HMGB1, STAT3 and p-STAT3 were detected by Western blotting. The expression of vascular endothelial growth factorA(VEGF-A) and microvascularization were detected by immunohistochemistry. Results: Compared with the control group, the growth of tumor volume slowed down in HMGB1 siRNA group, and on the 21st day, the tumor volume of HMGB1-siRNA group was significantly smaller than that of the control group (P<0.05). HMGB1-siRNA successfully knocked down the expression of HMGB1 mRNA in transplanted
tumor tissue. The apoptosis rate of tissue cells in HMGB1-siRNA group was significantly increased ([34±8]% vs [6±2]%, P=0.04), and the expressions of HMGB1 and p-STAT3 were significantly reduced (P<0.05). The expression of VEGF-Aand the number of microvessels were significantly lower than those of the control group (both P<0.05). Conclusion: Knockdown of HMGB1 gene reduces the expression of VEGF-A and microvessel formation possibly by inhibiting the HMGB1/STAT3 signaling pathway, thereby promoting the apoptosis of tumor tissues and slowing the growth of xenografts.