Physiologically relevant miRNAs in mammalian oocytes are rare and highly abundant

miRNAs, ~22nt small RNAs associated with Argonaute (AGO) proteins, are important negative regulators of gene expression in mammalian cells. However, mammalian maternal miRNAs show negligible repressive activity and the miRNA pathway is dispensable for oocytes and maternal‐to‐zygotic transition. The stoichiometric hypothesis proposed that this is caused by dilution of maternal miRNAs during oocyte growth. As the dilution affects miRNAs but not mRNAs, it creates unfavorable miRNA:mRNA stoichiometry for efficient repression of cognate mRNAs. Here, we report that porcine ssc‐miR‐205 and bovine bta‐miR‐10b are exceptional miRNAs, which resist the diluting effect of oocyte growth and can efficiently suppress gene expression. Additional analysis of ssc‐miR‐205 shows that it has higher stability, reduces expression of endogenous targets, and contributes to the porcine oocyte‐to‐embryo transition. Consistent with the stoichiometric hypothesis, our results show that the endogenous miRNA pathway in mammalian oocytes is intact and that maternal miRNAs can efficiently suppress gene expression when a favorable miRNA:mRNA stoichiometry is established.     

Construction of PARPi Resistance-related Competing Endogenous RNA Network

Objective: Ovarian cancer is a kind of common gynecological malignancy in women. PARP inhibitors (PARPi) have been approved for ovarian cancer treatment. However, the primary and acquired resistance have limited the application of PARPi. The mechanisms remain to be elucidated.Methods: In this study, we characterized the expression profiles of mRNA and nonconding RNAs (ncRNAs) and constructed the regulatory networks based on RNA sequencing in PARPi Olaparib-induced ovarian cancer cells.Results: We found that the functions of the differentially expressed genes were enriched in “PI3K/AKT signaling pathway,” “MAPK signaling pathway” and “metabolic process”. The functions of DELs (cis) were enriched in “Human papillomavirus infection”“tight junction” “MAPK signaling pathway”. As the central regulator of ceRNAs, the differentially expressed miRNAs were enriched in “Human papillomavirus infection” “MAPK signaling pathway” “Ras signaling pathway”. According to the degree of interaction, we identified 3 lncRNAs, 2 circRNAs, 7 miRNAs, and 12 mRNA as the key regulatory ceRNA axis, in which miR-320b was the important mediator.Conclusion: Here, we revealed the key regulatory lncRNA (circRNA)-miRNA-mRNA axis and their involved pathways in the PARPi resistant ovarian cancer cells. These findings provide new insights into exploring the ceRNA regulatory networks and developing new targets for PARPi resistance.     

microRNA生物合成的调控进展——TGFβ/Smad信号途径的作用

microRNA（miRNA）是一类非编码的小分子单链RNA,主要通过转录后抑制靶基因表达调节各种生物功能。miRNA表达水平在正常发育过程中以及在癌症及心血管疾病等各种疾病中发生变化。目前控制miRNA生物合成的信号途径以及调节机制尚未完全阐明。miRNA基因转录后在大蛋白复合体的介导下经一系列协调加工过程形成成熟的miRNA。近来发现转化生长因子β（TGFβ）信号途径的转导因子Smad蛋白在细胞核内调节miRNA的加工处理过程起重要作用。本文主要综述TGFβ/Smad信号途径在miRNA生物合成中的调节作用。