The F-box protein 22 (FBXO22), an F-box E3 ligase, has been identified to be critically involved in carcinogenesis. However, a systematic assessment of the role of FBXO22 across human cancers is lacking. Here, we performed a pan-cancer analysis to explore the role of FBXO22 in 33 cancer types using multiomic data from The Cancer Genome Atlas (TCGA). First, we found that high FBXO22 expression in multiple cancers was closely associated with poor overall survival and relapse-free survival. Next, we identified ten proteins that interact with FBXO22 and 13 of its target substrates using the STRING database and a literature search to explore the regulatory role of FBXO22 in tumorigenesis. Genes encoding these proteins were found to be significantly enriched in cell cycle negative regulation and ubiquitination pathways. This was confirmed in nonsmall cell lung cancer A549 cells, where FBXO22 overexpression enhanced cyclin-dependent kinase 4 (CDK4) protein levels and promoted cell proliferation. Similarly, overexpression or interference of FBXO22 changed the protein level of one of its substrates, PTEN. Additionally, we found that FBXO22 mutations were accompanied by altered substrate expression, especially in uterine corpus endometrial carcinoma and lung adenocarcinoma; endometrial carcinoma patients with FBXO22 genetic alterations also had better overall and relapse-free survival. Notably, FBXO22 methylation levels were also decreased in most tumors, and hypomethylation of FBXO22 was associated with poor overall survival, relapse-free interval, and progression-free interval in pancreatic adenocarcinoma. Finally, we analyzed the correlation between the abundance of tumor infiltrating lymphocytes (TILs) and FBXO22 expression, copy number variation, and methylation. Multiple algorithms revealed that high FBXO22 expression was associated with lower TIL levels, especially in lung adenocarcinoma, lung squamous cell carcinoma, and sarcoma. Taken together, our findings demonstrate that FBXO22 degrades tumor suppressor genes by ubiquitination and inhibits the cell cycle to promote nonsmall cell lung cancer progression. Our study also provides a relatively comprehensive understanding of the oncogenic role of FBXO22 in different tumors.

Neuroblastoma breakpoint family, member 1 (NBPF1), appears to be a double-edged sword with regard to its role in carcinogenesis. On the one hand, the tumor-suppressing functions of NBPF1 have been definitively observed in neuroblastoma, prostate cancer, cutaneous squamous cell carcinoma, and cervical cancer. On the other hand, there is evidence that NBPF1 regulates the colony formation, invasion, and maintenance of liver cancer cells and hence functions as an oncogene. The roles of NBPF1 are strictly dependent on the biological context and type of organization. However, a systematic pan-cancer analysis has thus far not been undertaken, and the significance of NBPF1 in the occurrence and progression of many malignancies is uncertain. In this paper, bioinformatics techniques were employed to analyze NBPF1 expression across different cancers and investigate the relationship between NBPF1 and clinical features, prognosis, genetic alteration, and tumor immune microenvironment, respectively. Our results show that NBPF1 is variably expressed in distinct tumor tissues and is also closely linked to clinical outcomes. In particular, compared to other tumor types, there was a strong negative correlation between NBPF1 expression and various components of the tumor microenvironment in adrenocortical carcinoma (ACC). We thus developed an NBPF1-derived immune risk model based on NBPF1-related immune genes; ACC patients with a high-risk score tended to have a poorer prognosis, accompanied by immune hyporesponsiveness. NBPF1 can be used as a prognostic biomarker for multiple cancers. Moreover, anti-NBPF1 immunotherapy may be suitable for treating ACC patients.

Talaromyces amestolkiae is an important fungal species owing to its ubiquity in soils, plants, air, and food. In this study, we identified a novel six-segmented polymycovirus, Talaromyces amestolkiae polymycovirus 1 (TaPmV-1). Each of the double-stranded (ds) RNA segments of TaPmV-1 contained a single open reading frame, and the proteins encoded by dsRNA1, dsRNA2, dsRNA3, and dsRNA 5 shared significant amino acid identities of 56, 40, 47, and 43%, respectively, with the corresponding proteins of Aspergillus fumigatus polymycovirus-1(AfuPmV-1). DsRNA1, dsRNA3, and dsRNA5 of TaPmV-1 encoded an RNA-dependent RNA polymerase (RdRp), a viral methyltransferase, and a PAS-rich protein, respectively. The functions of the proteins encoded by dsRNA2, dsRNA4, and dsRNA6 have not been elucidated. Comparison of the virus-infected strain LSH3 with virus-cured strain LSHVF revealed that infection with TaPmV-l may reduce the production of red pigments and induce the clustering of fungal sclerotia. Furthermore, transcriptomic analyses demonstrated that infection with TaPmV-l downregulated the expression of transcripts related to metabolism, and may correlate with the reduced production of red pigments and clustering of sclerotia in T. amestolkiae. These results of this study provide novel insights into the mechanism of fungal gene regulation by polymycovirus infections at the transcriptome level, and this study is the first to report a novel polymycovirus of T. amestolkiae.