OTU deubiquitinase 5 (OTUD5), as a member of the ovarian tumor protease (OTU) family, was previously reported to play important roles in DNA repair and immunity. However, little is known about its function in tumors. Cervical cancer is a malignant tumor that seriously endangers the lives of women. Here, we found that low expression of OTUD5 in cervical cancer is associated with poor prognosis. Its expression is associated with tumor stage, metastatic nodes and tumor subtypes such as those related to the phosphatidylinositol–3–kinase (PI3K)–AKT signaling, epithelial-mesenchymal transition (EMT) and hormones. In addtion, we analyzed the coexpressed genes, related miRNAs, transcription factors, kinases, E3s and interacting proteins of OTUD5. We demonstrated that OTUD5 affects the expression levels of WD repeat domain 45 (WDR45), ubiquitin-specific peptidase 11 (USP11), GRIP1 associated protein 1 (GRIPAP1) and RNA binding motif protein 10 (RBM10). Moreover, hsa-mir-137, hsa-mir-1913, hsa-mir-937, hsa-mir-607, hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5. Furthermore, we performed enrichment analysis of 22 coexpressed genes, 33 related miRNAs and 30 interacting proteins. In addition to ubiquitination and immunology related processes, they also participate in Hippo signaling, insulin signaling, EMT, histone methylation and phosphorylation kinase binding. Our study for the first time analyzed the expression of OTUD5 in cervical cancer and its relationship with clinicopathology and provided new insights for further study of its regulatory mechanism in tumors.

Lorises are a group of globally threatened strepsirrhine primates that exhibit many unusual physiological and behavioral features, including a low metabolic rate, slow movement, and hibernation. Here, we assembled a chromosome-level genome sequence of the pygmy loris ( Xanthonycticebus pygmaeus ) and resequenced whole genomes from 50 pygmy lorises and 6 Bengal slow lorises ( Nycticebus bengalensis ). We found that many gene families involved in detoxification have been specifically expanded in the pygmy loris, including the GSTA gene family, with many newly derived copies functioning specifically in the liver. We detected many genes displaying evolutionary convergence between pygmy loris and koala, including PITRM1. Significant decreases in PITRM1 enzymatic activity in these two species may have contributed to their characteristic low rate of metabolism. We also detected many evolutionarily convergent genes and positively selected genes in the pygmy loris that are involved in muscle development. Functional assays demonstrated the decreased ability of one positively selected gene, MYOF, to up-regulate the fast-type muscle fiber, consistent with the lower proportion of fast-twitch muscle fibers in the pygmy loris. The protein product of another positively selected gene in the pygmy loris, PER2 , exhibited weaker binding to the key circadian core protein CRY, a finding that may be related to this species’ unusual circadian rhythm. Finally, population genomics analysis revealed that these two extant loris species, which coexist in the same habitat, have exhibited an inverse relationship in terms of their demography over the past 1 million years, implying strong interspecies competition after speciation.

Aberrant alternative splicing (AS) profoundly affects tumorigenesis and cancer progression. Serine/arginine‐rich splicing factor 3 (SRSF3) regulates the AS of precursor mRNAs and acts as a proto‐oncogene in many tumors, but its function and potential mechanisms in cervical cancer remain unclear. Here, we found that SRSF3 was highly expressed in cervical cancer tissues and that SRSF3 expression was correlated with prognosis after analyses of the The Cancer Genome Atlas and GEO databases. Furthermore, knockdown of SRSF3 reduced the proliferation, migration, and invasion abilities of HeLa cells, while overexpression of SRSF3 promoted proliferation, migration, and invasion of CaSki cells. Further studies showed that SRSF3 mediated the variable splicing of exon 12 of the transcriptional cofactor DEAD‐box helicase 5 (DDX5). Specifically, overexpression of SRSF3 promoted the production of the pro‐oncogenic spliceosome DDX5‐L and repressed the production of the repressive spliceosome DDX5‐S. Ultimately, both SRSF3 and DDX5‐L were able to upregulate oncogenic AKT expression, while DDX5‐S downregulated AKT expression. In conclusion, we found that SRSF3 increased the production of DDX5‐L and decreased the production of DDX5‐S by regulating the variable splicing of DDX5. This, in turn promoted the proliferation, migration, and invasion of cervical cancer by upregulating the expression level of AKT. These results reveal the oncogenic role of SRSF3 in cervical cancer and emphasize the importance of the SRSF3‐DDX5‐AKT axis in tumorigenesis. SRSF3 and DDX5 are new potential biomarkers and therapeutic targets for cervical cancer.