[Retracted] Downregulation of miR­30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer.

[This retracts the article DOI: 10.3892/ol.2017.7114.].

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.

Downregulation of miR-30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer.

Accumulating studies have revealed that microRNAs serve crucial roles in cancer development and progression. MicroRNA-30a (miR-30a) has been implicated in various cancer types. However, the role of miR-30a in cervical cancer remains unclear. In the current study, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed that miR-30a was significantly downregulated in cervical cancer tissues compared with adjacent normal tissues, and in the cervical cancer cell lines HeLa, SiHa and Ca-Ski compared with GH329 normal cervical epithelial cells. A functional assay using miR-30a mimic demonstrated that miR-30a could inhibit the growth and invasion of cervical cancer cells. Additionally, bioinformatics-based prediction and luciferase reporter assays indicated that MEF2D is a direct target of miR-30a. Transfection with miR-30a reduced the mRNA expression and protein levels of MEF2D, as determined using RT-qPCR and western blot analyses. Furthermore, MEF2D expression was negatively correlated with that of miR-30a in cervical cancers. Overall, the present study demonstrated that miR-30a functions as a tumor suppressor by targeting MEF2D in cervical cancer, which may provide the basis for a prognostic biomarker or therapeutic strategy for cervical cancer.

Nexrutine inhibits cancer cell growth as a consequence of mitochondrial damage and mitophagy.

BACKGROUND/AIMS: Nexrutine is an herbal extract of Phellodendron amurense and has been used as nutrient supplement in China as well as America. Potential protection effect of Nexrutine has been reported. METHODS: To investigate the mechanism of Nexrutine, we used the HeLa, U2OS and HCT116 as a model. Based on the acidification of cell culture media, we examined the lactate, mitochondria damage as well as mitophagy status by corresponding assay. RESULTS: Our data suggest that Nexrutine alters the cellular glucose metabolism to promote lactate production. This effect is caused by mitochondrial damage, not an alteration to lactate dehydrogenase activity. As a result of the mitochondrial damage, cell proliferation was inhibited and was associated with an elevation in p21/p27 proteins, which are both important cell cycle inhibitors. As another consequence of the mitochondrial damage, mitophagy was highly activated in Nexrutine-treated cells in a dose-dependent manner. When the autophagy pathway was blocked by siRNAs against BECN1 or ATG7, the growth inhibition caused by Nexrutine was reversed. CONCLUSION: Our study revealed that autophagy plays an important role in the inhibition of cancer cell proliferation by Nexrutine.

[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.