Pan-cancer analysis reveals potential of FAM110A as a prognostic and immunological biomarker in human cancer

BackgroundDespite great success, immunotherapy still faces many challenges in practical applications. It was previously found that family with sequence similarity 110 member A (FAM110A) participate in the regulation of the cell cycle and plays an oncogenic role in pancreatic cancer. However, the prognostic value of FAM110A in pan-cancer and its involvement in immune response remain unclear.MethodsThe Human Protein Atlas (HPA) database was used to detect the expression of FAM110A in human normal tissues, the Tumor Immune Estimation Resource (TIMER) and TIMER 2.0 databases were used to explore the association of FAM110A expression with immune checkpoint genes and immune infiltration, and the Gene Set Cancer Analysis (GSCA) database was used to explore the correlation between FAM110A expression and copy number variations (CNV) and methylation. The LinkedOmics database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Statistical analysis and visualization of data from the The Cancer Genome Atlas (TCGA) or the Genotype–Tissue Expression (GTEx) databases were performed using the R software (version 3.6.3). Clinical samples were validated using immunohistochemistry.ResultsFAM110A expression was elevated in most tumor tissues compared with that in normal tissues. CNV and methylation were associated with abnormal FAM110A mRNA expression in tumor tissues. FAM110A affected prognosis and was associated with the expression of multiple immune checkpoint genes and abundance of tumor-infiltrating immune cells across multiple types of cancer, especially in liver hepatocellular carcinoma (LIHC). FAM110A-related genes were involved in multiple immune-related processes in LIHC.ConclusionFAM110A participates in regulating the immune infiltration and affecting the prognosis of patients in multiple cancers, especially in LIHC. FAM110A may serve as a prognostic and immunological biomarker for human cancer

Current progress of Atractylodes macrocephala Koidz.: A review of its biogeography, PAO-ZHI processing, biological activities, biosynthesis pathways, and technology applications

The Atractylodes macrocephala Koidz. is a traditional Chinese rhizome herb, consumed for its well-known medicinal value. This review summarizes the recent research findings on biological activities, main biosynthesis pathways, PAO-ZHI processing, and technology application. The impact of biogeography led to significant differences in phenotypes and chemotypes. The PAO-ZHI processing also significantly affected A. macrocephala rhizome (AMR) bioactivity. A further systemic mechanistic investigation is required. Besides, new AMR polysaccharides with immunomodulatory effects, improving gastrointestinal function, and antitumor activity are constantly being isolated and characterized. Also, the discovery of novel families of compounds, such as the atractylenolides possessing antitumor, neuroprotective, immunomodulatory, and anti-inflammatory activities, is still ongoing work. Advanced genetics tools, such as in-depth transcriptomics, provide the basis for exploring A. macrocephala resources' functional genetic and molecular regulatory mechanisms. Still, some pathways are more elusive than others, and the biosynthetic pathways of sesquiterpenes, one of the prominent active families, still present a challenge in AMR and other plants. We propose here new directions and opportunities to advance current research in AMR. This review lays the theoretical foundation for fully developing and utilizing A. macrocephala resources

TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer

Abstract Background The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. Methods Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). Results In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. Conclusions Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC