Premature ovarian failure (POF) is a long-term adverse effect of chemotherapy treatment. However, current available treatment regimens are not optimal. Emerging evidence suggests that bone marrow-derived mesenchymal stem cells (BMSCs) could restore the structure and function of injured tissues, but the homing and restorative effects of BMSCs on chemotherapy injured ovaries are still not clear. In this study, we found that granulosa cell (GC) apoptosis induced by cisplatin was reduced when BMSCs were migrated to granulosa cells (GCs) in vitro. Chemotherapy-induced POF was induced by intraperitoneal injection of cisplatin in rats. BMSCs labeled with enhanced green fluorescent protein (EGFP) were injected into the rats via the tail vein to investigate the homing and distribution of BMSCs in vivo. The number of BMSCs in the ovarian hilum and medulla was greater than in the cortex, but no BMSCs were found in the follicles and corpus lutea. In addition, the BMSCs treatment group’s antral follicle count and estradiol levels increased after 30 days, compared with the POF group. Hence, our study demonstrates that intravenously delivered BMSCs can home to the ovaries, and restore its structure and function in POF model rats.
MicroRNAs (miRNAs) are potential therapeutic targets in endometrial cancer, but the difficulties associated with their delivery to tumor target cells have hampered their applications. Human umbilical cord mesenchymal stem cells (hUCMSCs) have a well-recognized tumor-homing ability, emphasizing the capacity of tumor-targeted delivery of extracellular vesicles. hUCMSCs release extracellular vesicles rich in miRNAs, which play a vital role in intercellular communication. The purpose of this study was to verify a potential tumor suppressor microRNA, miR-302a, and engineered hUCMSC extracellular vesicles enriched with miR-302a for therapy of endometrial cancer. Here, we observed that miR-302a was significantly downregulated in endometrial cancer tissues when compared with adjacent tissues. Overexpression of miR-302a in endometrial cancer cells robustly suppressed cell proliferation and migration. Meanwhile, the proliferation and migration were significantly inhibited in endometrial cancer cells when cultured with miR-302a-loaded extracellular vesicles derived from hUCMSCs. Importantly, our data showed that engineered extracellular vesicles rich in miR-302 significantly inhibited the expression of cyclin D1 and suppressed AKT signaling pathway in endometrial cancer cells. These results suggested that exogenous miR-302a delivered by hUCMSC-derived extracellular vesicles has exciting potential as an effective anticancer therapy.
Background: Cisplatin resistance (DDP-resistance) remains one of the major causes of poor prognosis in females with ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of cellular processes, including chemoresistance. The aim of this study was to explore the role of HOX transcript antisense RNA (HOTAIR) in DDP-resistant ovarian cancer cells. Methods: DDP-resistant ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. Real-time PCR, western blot, dual-luciferase reporter assay, and flow cytometry were then used to evaluate the effect of HOTAIR/miR-138-5p axis on chemoresistance of DDP-resistant ovarian cancer cells to DDP. Results: We found that HOTAIR was upregulated in DDP-resistant cells, while miR-138-5p was downregulated. Knockdown of HOTAIR increased the expression of miR-138-5p in DDP-resistant cells and miR-138-5p is directly bound to HOTAIR. Upregulation of miR-138-5p induced by HOTAIR siRNA or by its mimics enhanced the chemosensitivity of DDP-resistant cells and decreased the expression of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) and SIRT1 (sirtuin 1). Furthermore, the HOTAIR silencing-induced chemosensitivity of DDP-resistant cells was weakened by miR-138-5p inhibitor. Conclusions: These data demonstrate that HOTAIR acts as a sponge of miR-138-5p to prevent its binding to EZH2 and SIRT1, thereby promoting DDP-resistance of ovarian cancer cells. Our work will shed light on the development of therapeutic strategies for ovarian cancer treatment.
BackgroundPolycystic ovary syndrome (PCOS) significantly affects women’s health and well-being. To explore the pharmacological basis of the Erxian decoction (EXD) action in PCOS therapy, a network interaction analysis was conducted at the molecular level.MethodsThe active elements of EXD were identified according to the oral bioavailability and drug-likeness filters from three databases: traditional Chinese medicine system pharmacology analysis platform, TCM@taiwan and TCMID, and their potential targets were also identified. Genes associated with PCOS and established protein–protein interaction networks were mined from the NCBI database. Finally, significant pathways and functions of these networks were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to determine the mechanism of action of EXD.ResultsSeventy active compounds were obtained from 981 ingredients present in the EXD decoction, corresponding to 247 targets. In addition, 262 genes were found to be closely related with PCOS, of which 50 overlapped with EXD and were thus considered therapeutically relevant. Pathway enrichment analysis identified PI3k-Akt, insulin resistance, Toll-like receptor, MAPK and AGE-RAGE from a total of 15 significant pathways in PCOS and its treatment.ConclusionsEXD can effectively improve the symptoms of PCOS and our systemic pharmacological analysis lays the experimental foundation for further clinical applications of EXD.
Leptin and ObR are overexpressed in EC, and their expressions are associated with malignancy, invasion, and metastasis of EC. Thus, leptin and ObR may be important indicators in EC.
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