CacyBP promotes the development of lung adenocarcinoma by regulating OTUD5.

Lung cancer is the most common and lethal malignancy, with lung adenocarcinoma accounting for approximately 40% of all cases. Despite some progress in understanding the pathogenesis of this disease and developing new therapeutic approaches, the current treatments for lung adenocarcinoma remain ineffective due to factors such as high tumour heterogeneity and drug resistance. Therefore, there is an urgent need to identify novel therapeutic targets. Calcyclin-binding protein (CacyBP) can regulate a variety of physiological processes by binding to different proteins, but its function in lung adenocarcinoma is unknown. Here, we show that CacyBP is highly expressed in lung adenocarcinoma tissues, and high CacyBP expression correlates with poorer patient survival. Moreover, overexpression of CacyBP promoted the proliferation, migration and invasion of lung adenocarcinoma cell lines. Further mechanistic studies revealed that CacyBP interacts with the tumour suppressor ovarian tumour (OTU) deubiquitinase 5 (OTUD5), enhances the ubiquitination and proteasomal degradation of OTUD5 and regulates tumourigenesis via OTUD5. In conclusion, our study reveals a novel mechanism by which CacyBP promotes tumourigenesis by increasing the ubiquitination level and proteasome-dependent degradation of OTUD5, providing a potential target for the treatment of lung adenocarcinoma.

Splicing factor SRSF3 promotes the progression of cervical cancer through regulating DDX5.

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.

Aberrant expression and regulatory network of splicing factor-SRSF3 in tumors.

Alternative splicing facilitates the splicing of precursor RNA into different isoforms. Alternatively spliced transcripts often exhibit antagonistic functions or differential temporal or spatial expression patterns. There is increasing evidence that alternative splicing, especially by the serine-arginine rich (SR) protein family, leads to abnormal expression patterns and is closely related to the development of cancer. SRSF3, also known as SRp20, is a splicing factor. Through alternative splicing, it plays important roles in regulating various biological functions, such as cell cycle, cell proliferation, migration and invasion, under pathological and physiological conditions. Deregulation of SRSF3 is an essential feature of cancers. SRSF3 is also considered a candidate therapeutic target. Therefore, the involvement of abnormal splicing in tumorigenesis and the regulation of splicing factors deserve further analysis and discussion. Here, we summarize the function of SRSF3-regulated alternative transcripts in cancer cell biology at different stages of tumor development and the regulation of SRSF3 in tumorigenesis.

Analysis of deubiquitinase OTUD5 as a biomarker and therapeutic target for cervical cancer by bioinformatic analysis.

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.