RAMP2-AS1 inhibits CXCL11 expression to suppress malignant phenotype of breast cancer by recruiting DNMT1 and DNMT3B.

BACKGROUND: Breast cancer is the most common malignancy in women populations. METHODS: RAMP2-AS1 and CXCL11 expression in breast cancer tissues and cells were determined using RT-qPCR or Western blot. RIP analysis confirmed the interaction between DNMT1, DNMT3B and RAMP2-AS1. ChIP assay verified that RAMP2-AS1 recruited DNMT1 and DNMT3B to the promoter region of CXCL11. FISH detected the sub-localization of RAMP2-AS1 in breast cancer cells. Bisulfite sequencing PCR (BSP) tested the methylation level of CXCL11. The cell viability, proliferation, migration and apoptosis were assessed by CCK-8, colony formation, transwell and flow cytometry assays, respectively. IHC was performed to evaluate the expression of Ki67, CXCL11, MMP2 in tumor tissues. RESULTS: The level of RAMP2-AS1 was decreased in breast cancer tissues and cells, whereas CXCL11 was highly expressed. Patients with decreased RAMP2-AS1 had a poor prognosis. RAMP2-AS1 inhibited breast cancer cell malignant phenotype. Besides, RAMP2-AS1 regulated the methylation of CXCL11 by recruiting DNMT1 and DNMT3B to the promoter region of CXCL11. RAMP2-AS1 overexpression suppressed the malignant phenotype through CXCL11 and inhibited tumor growth in vivo. CONCLUSION: RAMP2-AS1 suppresses breast cancer malignant phenotype via DNMT1 and DNMT3B mediated inhibition of CXCL11.

[Evaluation on clinical effectiveness of modified laparoscopic sacral colpopexy].

OBJECTIVE: To study clinical curative effect and complications of modified laparoscopic sacral colpopexy and evaluate the efficacy and safety of this procedure in treatment of pelvic organ prolapse (POP) . METHODS: From Jan. 2008 to Sept. 2012, 66 patients who had undergone modified laparoscopic sacral colpopexy for POP in the first affiliated hospital of Guangzhou medical university were studied retrospectively. Primary outcomes were assessed with POP quantitation ( POP-Q) system that was measured before or after operation respectively to evaluate the objective cure rate and recurrence rate.Secondary outcomes were measured by the pelvic floor distress inventory short form (PFDI-20) to evaluate the subjective cure rate, as well as to evaluate the improvement of postoperative lower urinary tract symptoms. RESULTS: Sixty-three patients were followed up for 6 to 57 months, and the median follow-up time was 16 months, the overall objective cure rate was 95% (60/63). Postoperative each indicator point was reset anatomically according to POP-Q, the overall objective cure rate was 90% (57/63), and the total recurrence rate was 10% (6/63). The median postoperative vaginal length was slightly shortened than preoperative length[7.5 cm versus 8.0 cm, P < 0.01]; the median score of postoperative PFDI-20 was obviously improved compared to the preoperative (21 versus 75 scores, P < 0.05); there was no statistically significant difference in POP-Q staging and questionnaire score at more than 3 years, >2- ≤ 3 years, >1- ≤ 2 years, <0.5-1 year after operation (P > 0.05). Among 23 patients with stress urinary incontinence (SUI) and 5 patients with mixed urinary incontinence (MUI), 15 cases underwent transvaginal tension free vaginal tape-obturator (TVT-O) procedure simultaneously, 13 cases did not. The cure rate of SUI was 14/15 and 10/13, respectively. CONCLUSIONS: Modified laparoscopic sacral colpopexy can not only reach the anatomical replacement stage but significantly improve the postoperative quality of life with high subjective and objective cure rate and few complications. The long-term curative effect is stable.