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Background: Poor endometrial receptivity is a major factor that leads to recurrent implantation failure. However, the traditional method cannot accurately evaluate endometrial receptivity. Various studies have indicated that microRNAs (miRNAs) are involved in multiple processes of embryo implantation, but the role of miRNAs in endometrial receptivity in patients with recurrent implantation failure (RIF) remains elusive. In the present study, we investigated the presence of pinopodes and the roles of miR-30d-5p, suppressor of cytokine signalling 1 (SOCS1) and the leukaemia inhibitory factor (LIF) pathway in women with a history of RIF during the implantation window. Methods: Endometrial tissue samples were collected between January 2018 to June 2019 from two groups of women who underwent in vitro fertilisation and embryo transfer (IVF-ET) or frozen ET. The RIF group included 20 women who underwent ≥ 3 ETs, including a total of ≥ 4 good-quality embryos, without pregnancy, whereas the control group included 10 women who had given birth at least once in the past year. An endometrial biopsy was performed during the implantation window (LH + 7). The development of pinopodes in the endometrial biopsy samples from all groups was evaluated using scanning electron microscopy (SEM). Quantitative reverse transcription-polymerase chain reaction and western blotting were used to investigate the expression levels of miR-30d-5p, SOCS1, and the LIF pathway. Results: The presence of developed pinopodes decreased in patients with RIF on LH + 7. The expression level of miR-30d-5p decreased in the endometria during the implantation window of patients with RIF, whereas the mRNA and protein levels of SOCS1 were significantly higher in the RIF group than in the control group. Furthermore, a negative correlation was observed between the expression of miR-30d-5p and SOCS1 (r2 = 0.8362). In addition, a significant decrease in LIF and p-STAT3 expression was observed during the implantation window in patients with RIF. Conclusions: MiR-30d-5p and SOCS1 may be potential biomarkers for endometrial receptivity. Changes in pinopode development and abnormal expression of miR-30d-5p, SOCS1 and LIF pathway in the endometrium could be the reasons for implantation failure. [ABSTRACT FROM AUTHOR]

CircRNAs are associated with adriamycin (ADM) resistance in triple-negative breast cancer (TNBC), but the mechanism is unknown. Reverse transcription-quantitative PCR was applied to quantify circular RNA (circRNA)_0044556, microRNA (miR)-145 and NRAS proto-oncogene, GTPase (NRAS) in TNBC tissues and cells with or without ADM treatment. Following ADM treatment, the effects of circRNA_0044556 on the viability, ADM resistance, apoptosis and migration of TNBC cells were investigated by cell function experiments (Cell Counting Kit-8, flow cytometry and Transwell assays). The targeting relationship between circRNA_0044556 and miR-145 was investigated via bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation. The effects of the circRNA_0044556/miR-145 axis on the TNBC cells were revealed by rescue experiments. Correlations among circRNA_0044556, miR-145 and NRAS were analyzed by Pearson's correlation test. CircRNA_0044556 was highly expressed in TNBC tissues and cells with or without ADM-resistance. The overexpression of circRNA_0044556 promoted cell viability, ADM-resistance and migration, while inhibiting the apoptosis by sponging miR-145. Upregulation of miR-145 reversed the effects of circRNA_0044556 on the TNBC cells. CircRNA_0044556 was negatively correlated with miR-145 yet positively correlated with NRAS, the target gene of miR-145, in addition to the discovery suggesting the negative regulatory effects of circRNA_0044556 on miR-145. CircRNA_0044556 diminished the sensitivity of TNBC cells to ADM via the miR-145/NRAS axis. [ABSTRACT FROM AUTHOR]

ABSTRACT In eukaryotes, RNA N6‐methyladenosine (m6A) modification and microRNA (miRNA)‐mediated RNA silencing represent two critical epigenetic regulatory mechanisms. The m6A methyltransferase complex (MTC) and the microprocessor complex both undergo liquid–liquid phase separation to form nuclear membraneless organelles. Although m6A methyltransferase has been shown to positively regulate miRNA biogenesis, a mechanism of reciprocal regulation between the MTC and the microprocessor complex has remained elusive. Here, we demonstrate that the MTC and the microprocessor complex associate with each other through the METHYLTRANSFERASE B (MTB)–SERRATE (SE) interacting module. Knockdown of MTB impaired miRNA biogenesis by diminishing microprocessor complex binding to primary miRNAs (pri‐miRNAs) and their respective MIRNA loci. Additionally, loss of SE function led to disruptions in transcriptome‐wide m6A modification. Further biochemical assays and fluorescence recovery after photobleaching (FRAP) assay indicated that SE enhances the liquid–liquid phase separation and solubility of the MTC. Moreover, the MTC exhibited enhanced retention on chromatin and diminished binding to its RNA substrates in the se mutant background. Collectively, our results reveal the substantial regulatory interplay between RNA m6A modification and miRNA biogenesis. [ABSTRACT FROM AUTHOR]