TRIM11 regulated by m6A modification promotes the progression of cervical cancer by PHLPP1 ubiquitination.

Cervical cancer (CC) is a common cancer in women and a serious threat to women's lives. TRIM11 has been confirmed as a carcinogen in multiple cancers. Here, we will excavate the detailed mechanism of TRIM11 in CC. CC cell lines and nude mice were experimental subjects in this study. The abundance of genes and proteins was detected using qRT-PCR, western blot, and IHC. Cell proliferation, migration, and invasion were determined by CCK-8 assay, wound healing assay, and Transwell, respectively. The interactions among METTL14, TRIM11, and PHLPP1 were confirmed using RIP and co-IP, respectively. The stability of TRIM11 mRNA was examined by qRT-PCR with actinomycin D treatment. The m6A level of TRIM11 was detected by MeRIP assay. Results showed that TRIM11 levels were elevated in CC cells. TRIM11 depletion attenuated the proliferation, migration, and invasion of Hela and SiHa cells. Additionally, TRIM11 was modified with m6A, which was mediated by METTL14, and the stability of TRIM11 mRNA was enhanced by IGF2BP1 depending on the level of m6A modification. TRIM11 ubiquitinated PHLPP1 and led to reduced PHLPP1 expression at the protein level. PHLPP1 could further result in the dephosphorylation of AKT and inhibit AKT signaling. PHLPP1 knockdown neutralized TRIM11 silencing-mediated repression of malignant phenotypes of CC cells. TRIM11 mediated by the METTL14-IGF2BP1 axis promotes the AKT pathway to accelerate CC progression by mediating the ubiquitination of PHLPP, which might provide novel therapeutic targets for CC treatment.

Comparative study of tumor-free laparoscopic and open surgery in the treatment of early-stage cervical cancer. / æ— ç˜¤åŒ–è ¹è ”é•œæ‰‹æœ¯ä¸Žå¼€è ¹æ‰‹æœ¯æ²»ç–—æ—©æœŸå®«é¢ˆç™Œçš„å¯¹æ¯”ç ”ç©¶ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Laparoscopic surgery for cervical cancer has the advantages of little blood loss and rapid recovery, but its therapeutic effect is still controversial. This study aims to analyze the surgical procedure and clinical efficacy of tumor-free laparoscopic radical hysterectomy without a uterine manipulator for early-stage cervical cancer, and to explore the indications of laparoscopic surgery for cervical cancer. METHODS: This study was a retrospective study. The data of patients who underwent radical hysterectomy for early-stage cervical cancer admitted to Hunan Provincial Maternal and Child Health Care Hospital from July 2019 to December 2021 were collected. According to 2018 the International Federation of Gynecology and Obstetrics (FIGO) clinical staging, all patients were in IA1 with lymphovascular invasion, IA2, and IB1 stage. Among them, 45 patients underwent tumor-free laparoscopic radical hysterectomy without a uterine manipulator (laparoscopy group) and 16 patients underwent open surgery (open surgery group). Patients were followed up for 12-41 months. The differences between the 2 groups in terms of operative time, bleeding volume, extent of surgical resection, surgical complications, and prognosis were compared and analyzed. RESULTS: Compared to the open surgery group, the laparoscopy group had significantly shorter operation time and less intraoperative blood loss (both P<0.001). There were no significant differences between the 2 groups in terms of the length of excised uterosacral ligaments, cardinal ligaments, vagina, and the number of excised lymph nodes (all P>0.05). The incidence of postoperative complications did not differ significantly between the groups (P>0.05). No death or recurrence occurred in the 2 groups during the follow-up period. The overall survival rate and disease-free survival rate were both 100%. CONCLUSIONS: For early-stage cervical cancer with a diameter ≤2 cm, tumor-free laparoscopic radical hysterectomy without a uterine manipulator is safe and feasible, and the short-term outcomes is no less than that of open surgery.

[Reasonable surgical approach for grade III cervical intraepithelial neoplasia].

OBJECTIVE: To analyze the clinical pathologic characteristics of cervical intraepithelial neoplasia grade III (CINIII ) and to explore optimal surgery for CINIII patients. METHODS: The clinical pathologic characteristics, surgical treatments, prognosis and history of 383 CINIII patients, who hospitalized from August 2005 to December 2010, were reviewed and analyzed. Among the patients, 213 (55.6%) received cold-knife conization surgery and 170 (44.4%) received ordinary electric knife conization surgery. RESULTS: There was no significant statistic difference between cold-knife conization group and ordinary electric-knife conization group on the level of clearance of the pathologic tissues and the cervical cone diameter and cone high. Intraoperative blood loss was (13.1±5.2) mL and (25.5±17.2) mL. Bleeding of electric knife conization group, compared with that of the cold knife conization group, decreased by nearly 50%. The difference between the 2 groups was significant (P<0.01). Pathological examination after conization operation indicated that 350 out of the 383 patients didn't show pathological upgrade while 33 patients showed pathological development, among which 21 were diagnosed with invasive cervical cancer at Ia1 clincal stage, 7 atIa2 clincal stage and 5 atIb1 clincal stage. In 3 cases (14.3%) Ia1 cervical cancer patients, fertility requirements and negative margins with cervical conization were closely followed up, and one patient (4.8%) with positive margin and fertility requirements had re-conecut. The remaining 17 (80.9%) had resected the uterus outside the fascia (or plus attachments) . All the 12 patients with invasive cervical cancer at Ia2 orIb1 clinical stage received radical hysterectomy. No tumor recurrence was observed in the 383 patients. CONCLUSION: Treatment optimazation of CINIII patients should be based on clinical pathological diagnosis and individual requirements. Both cervical conization surgery and total hysterectomy have been proved safe and practical for CINIII patients.