FTO protects human granulosa cells from chemotherapy-induced cytotoxicity.

BACKGROUND: Premature ovarian failure (POF) is a serious problem for young women who receive chemotherapy, and its pathophysiological basis is the dysfunction of granulosa cells. According to previous reports, menstrual-derived stem cells (MenSCs) can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF. Fat mass- and obesity-associated (FTO) was reported to be associated with oocyte development and maturation. FTO was decreased in POF and may be a biomarker for the occurrence of POF. Knockdown of FTO in granulosa cells promoted cell apoptosis and inhibited proliferation. But the relationship between FTO and ovarian repair was still unclear. This study was aimed at investigating the FTO expression level and the role of FTO in the MenSCs recovering the function of injured granulosa cells. METHOD: First, cisplatin was used to establish a granulosa cell injury model. Then, the MenSCs and injured granulosa cell coculture model and POF mouse model were established in this study to explore the role of FTO. Furthermore, gain- and loss-of-function studies, small interfering RNA transfection, and meclofenamic acid (MA), a highly selective inhibitor of FTO, studies were also conducted to clarify the regulatory mechanism of FTO in granulosa cells. RESULTS: MenSCs coculture could improve the function of injured granulosa cells by increasing the expression of FTO. MenSCs transplantation restored the expression of FTO in the ovaries of POF mice. Overexpression of FTO restored the injured cell proliferation and decreased apoptosis by regulating the expression of BNIP3. Down-regulation of FTO got the opposite results. CONCLUSIONS: In the treatment of MenSCs, FTO has a protective effect, which could improve the viability of granulosa cells after cisplatin treatment by decreasing the expression of BNIP3. Meanwhile, FTO may provide new insight into therapeutic targets for the chemotherapy-induced POF.

[Role of miR-145-5p Targeting ARK5 in Regulating the Proliferation and Apoptosis of Human Epithelial Ovarian Cancer Cells].

Objective To explore the effect of miR-145-5p on the proliferation and apoptosis of human ovarian cancer cells and the possible molecular mechanisms involved.Methods Real-time quantitative PCR was performed to detect the expression of miR-145-5p in ovarian epithelial cells and ovarian cancer cells.CCK-8 and flow cytometry were used to detect the effects of miR-145-5p overexpression on the proliferation and apoptosis of ovarian cancer cells.TargetScan was employed to predict the target genes of miR-145-5p.Western blotting,dual luciferase reporter assay and rescue experiment were employed to predict and verify the underlying molecular mechanism of miR-145-5p function.Results The expression of miR-145-5p in ovarian cancer cells was significantly lower than that in normal ovarian epithelial cells(t=4.345,P=0.049).Compared with the control group,the overexpression of miR-145-5p reduced the proliferation rate(t=-15.790,P<0.001)and increased the apoptosis rate(t=5.433,P=0.032)of ovarian cancer cells.ARK5 was predicted as the direct target gene of miR-145-5p(t=4.583,P=0.010).The cells with ARK5 overexpression showed increased proliferation rate(t=27.290,P<0.001)and decreased apoptosis rate(t=-8.241,P=0.001).The overexpression of miR-145-5p can down-regulate the mRNA(t=-12.824,P<0.001)and protein(t=-4.792,P=0.001)levels of ARK5.The rescuing expression of ARK5 significantly offset the inhibitory effects of miR-145-5p on cell proliferation(t=15.580,P=0.004)and apoptosis(t=-12.470,P=0.006).Conclusion miR-145-5p may inhibit the proliferation and promote the apoptosis of ovarian cancer cells by targeting ARK5.

Sentinel lymph node mapping in early-stage cervical cancer: Meta-analysis.

BACKGROUND: The value of sentinel lymph node (SLN) mapping for early-stage cervical cancer remains controversial. Therefore, we collected data to investigate the feasibility and diagnostic accuracy of SLN in patients with early-stage (IA-IIA) cervical cancer. METHODS: We searched Embase, PubMed, and the Cochrane Library databases issued before June 1, 2020. The sample size of the selected study was at least 10 patients with early-stage (IA-IIA) cervical cancer, the pooled detection rates and the separate detection rate (overall detection rate, bilateral detection rate) using blue dye with Tc, technetium 99 (Tc) and indocyanine green (ICG) technique of early-stage cervical cancer was reported. R-3.6.1 software was used to evaluate pooled detection rate and sensitivity. RESULTS: Two thousand one hundred sixty-four patients included for analysis in 28 studies ranging from 12 to 405 patients. The combined overall detection rate of SLN mapping was 95% with a 72% pooled bilateral detection rate. The sensitivity of the combined overall detection rate of SLN mapping was 94.99% as well as a sensitivity of 72.43% bilateral detection rate. The overall detection rate of SLN was 96% for blue dye with Tc, 95% for Tc, 98% for ICG technique. The bilateral detection rate of SLN was 76% for blue dye with Tc, 63% for Tc, 85% for ICG technique. The sensitivity of the overall detection rate of SLN mapping was 97.76% as well as a sensitivity of 84.96% bilateral detection rate of ICG technique. CONCLUSION: In early-stage cervical cancer, overall detection rate of SLN mapping is elevated while bilateral detection rate is lower. The overall detection rate (98%) as well as bilateral rate (85%) of ICG seems to be a better SLN mapping technique among the method of SLN mapping (using blue dye with Tc, Tc or ICG). We believe SLN mapping may be considered contemporary technique which could provide additional benefits over traditional pelvic lymphadenectomy. While promising results in SLN mapping has been found, larger patient samples, including randomized studies, are required at the same time.