Circular RNA circ_RANBP9 exacerbates polycystic ovary syndrome via microRNA-136-5p/XIAP axis.

Polycystic ovary syndrome (PCOS) is an endocrine disease that affects the health of many women. Circular RNAs (circRNAs) are associated with the occurrence and progression of PCOS. This study aimed to explore the function of circ_RANBP9 in PCOS. First, the circ_RANBP9 level was found to be increased in the plasma of patients with PCOS and ovarian granulosa cells (GCs) using Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR). In GCs, loss of circ_RANBP9 decelerated proliferation and accelerated apoptosis of KGN and COV434 cells, as determined by MTT assay, colony formation assay, and flow cytometry. Furthermore, bioinformatics analysis showed that circ_RANBP9 and XIAP can be targeted by the microRNA, miR-136-5p. Luciferase reporter assay and RNA pull-down assay further verified the interaction between miR-136-5p and circ_RANBP9 or XIAP. Importantly, knockdown of circ_RANBP9 suppressed proliferation and promoted apoptosis of KGN and COV434 cells, whereas inhibition of miR-136-5p reversed these effects. Additionally, XIAP abolished the repression of proliferation and acceleration of apoptosis induced by miR-136-5p. The promotion of apoptosis was accompanied by upregulation of caspase-3 and Bax, and downregulation of Bcl-2, as estimated by western blotting. In conclusion, silencing of circ_RANBP9 inhibited GC proliferation and facilitated apoptosis by mediating the miR-136-5p/XIAP pathway. These findings provide a new theoretical basis for screening and treatment of PCOS.

TRIM71 binds to IMP1 and is capable of positive and negative regulation of target RNAs.

TRIM71 is an important RNA-binding protein in development and disease, yet its direct targets have not been investigated globally. Here we describe a number of disease and developmentally-relevant TRIM71 RNA targets such as the MBNL family, LIN28B, MDM2, and TCF7L2. We describe a new role for TRIM71 as capable of positive or negative RNA regulation depending on the RNA target. We found that TRIM71 co-precipitated with IMP1 which could explain its multiple mechanisms of RNA regulation, as IMP1 is typically thought to stabilize RNAs. Deletion of the NHL domain of TRIM71 impacted its ability to bind to RNA and RNAs bound by congenital hydrocephalus-associated point mutations in the RNA-binding NHL domain of TRIM71 clustered closely with RNAs bound by the NHL deletion mutant. Our work expands the possible mechanisms by which TRIM71 may regulate RNAs and elucidates further potential RNA targets.