The deubiquitinase enzyme RPN11 is involved in oncogenesis in various types of cancer. However, in breast cancer, the expression levels, prognostic relevance and biological function of RPN11 remains unclear. In the present study, RPN11 expression levels in breast cancer tissues and adjacent non‑tumor tissues were determined by reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining, and the association of RPN11 with clinicopathological features of breast cancer was evaluated. RPN11 expression was upregulated in breast cancer tissues compared with healthy tissues. Additionally, high expression levels of RPN11 may be an indicator of poor prognosis, as validated by a breast cancer cohort from the Gene Expression Omnibus database. Knockdown of RPN11 in MDA‑MB‑231 and T47D cells significantly reduced cell proliferation and enhanced G0/G1 arrest and apoptosis. Exogenous overexpression of RPN11 in MCF7 and Hs578T cells promoted cell growth and inhibited apoptosis. In addition, knockdown of RPN11 abrogated cell migration and reduced epithelial‑mesenchymal transition. In conclusion, these findings suggested that RPN11 may function as an oncogene and its upregulation in breast cancer suggests that it may be a therapeutic target.

Background Thyroid cancer causes considerable mortality and morbidity across the globe. Owing to the unavailability of biomarkers and the adverse effects of existing drugs, there is an urgent need to develop efficient chemotherapy for the treatment of thyroid cancers. Plants have served as exceptional source of drugs for the treatment of lethal diseases. The purpose of this study was to evaluate the anticancer effects of ferruginol against thyroid cancer cells. Material/Methods We monitored the cell proliferation rate using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using 4′,6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB), and annexin V/propidium iodide (PI) staining. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) levels were examined by fluorescence microscopy. Protein expressed was examined by western blotting. Results We found that ferruginol exerted potent antiproliferative action against thyroid cancer cells, and an IC 50 of 12 μM was observed for ferruginol against the MDA-T32 cell line. The toxic effects of ferruginol were less pronounced against normal cells. The anticancer effects of ferruginol were likely due to the induction of apoptosis which was also associated with upregulation of Bax and downregulation of Bcl-2. Ferruginol also caused ROS mediated alterations in the MMP of MDA-T32 cells. In MDA-T32 cells, ferruginol might also block the MAPK and PI3K/AKT signaling pathway, which is believed to be an important therapeutic target of anticancer drugs. Conclusions In conclusion, in view of the results of this study, it might be suggested that ferruginol might serve as an essential lead molecule for the treatment of thyroid cancer provided further in-depth studies especially studying ferruginol toxicological as well as in vivo studies are needed.

Human leukocyte antigen (HLA) class II plays critical roles in antigen presentation and the initiation of immune responses. However, the correlation between the HLA class II gene expression level and the survival of patients with breast cancer is still under investigation. We analyzed microarray and RNA-Seq data of breast cancer from the cancer genome atlas (TCGA), genotype-tissue expression (GTEx) and Oncomine databases by using bioinformatics tools. The expression of the HLA-DQA1, HLA-DQA2, and HLA-DQB2 genes was significantly upregulated in breast cancer. Higher expression levels of HLA class II genes in breast cancer, especially HLA-DOB and HLA-DQB2, were significantly associated with better overall survival. Furthermore, the expression of HLA class II genes was more closely associated with survival in breast cancer than in other cancer types. CD48 coexpressed with both HLA-DOB and HLA-DQB2 was also positively associated with the overall survival of breast cancer patients. The results indicated that HLA class II and CD48 may enhance antitumor immunity, and their expression patterns may serve as potential prognostic biomarkers and therapeutic targets in breast cancer.Abbreviations: CRC = colorectal cancer, DAVID = database for annotation, visualization and integrated discovery, GEPIA2 = gene expression profiling interactive analysis 2, GO = gene ontology, GTEx = genotype-tissue expression, HLA = human leukocyte antigen, HR = hazard ratio, OS = overall survival, STRING = search tool for the retrieval of interacting genes, TCGA = the cancer genome atlas.

Background Lung adenocarcinoma (LUAD) is the most prevalent non-small cell lung cancer (NSCLC). Patients with LUAD have a poor 5-year survival rate. The use of immune checkpoint inhibitors (ICIs) for the treatment of LUAD has been on the rise in the past decade. This study explored the prognostic role of butyrophilin-like 9 (BTNL9) in LUAD. Methods Gene expression profile of buytrophilins (BTNs) was determined using the GEPIA database. The effect of BTNL9 on the survival of LUAD patients was assessed using Kaplan-Meier plotter and OncoLnc. Correlation between BTNL9 expression and tumor-infiltrating immune cells (TILs) was explored using TIMER and GEPIA databases. Further, the relationship between BTNL9 expression and drug response was evaluated using CARE. Besides, construction and evaluation of nomogram based on BTNL9 expression and TNM stage. Results BTNL9 expression was downregulated in LUAD and was associated with a poor probability of 1, 3, 5-years overall survival (OS). In addition, BTNL9 expression was regulated at epigenetic and post-transcriptional modification levels. Moreover, BTNL9 expression was significantly positively correlated with ImmuneScore and ESTIMATEScore. Furthermore, BTNL9 expression was positively associated with infiltration levels of B cells, CD4+ T cells, and macrophages. Kaplan-Meier analysis showed that BTNL9 expression in B cells and dendritic cells (DCs) was significantly associated with OS. BTNL9 expression was significantly positively correlated with CARE scores. Conclusions These findings show that BTNL9 is a potential prognostic biomarker for LUAD. Low BTNL9 expression levels associated with low infiltration levels of naïve B cells, and DCs in the tumor microenvironment are unfavorable for OS in LUAD patients.

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Background: Butyrophilin (BTN) and butyrophilin-like (BTLN) belong to immunoglobulin superfamily, and also pertain the B7 co-stimulatory molecules family, which has multiple roles in immune modulation. Whether the BTNL9 expression in lung adenocarcinoma (LUAD) correlates with outcome has not been evaluated.Methods: Oncomine and GEPIA were used to analyze the BTNL9, while its mRNA expression in LUAD and corresponding adjacent tissues was investigated using TIMER. The clinical prognosis of BTNL9 was assessed in the GEPIA, Kaplan-Meier plotter, and OncoLnc. Besides, the correlation between BTNL9 and tumor-infiltrating immune cells (TILs) was analyzed using TIMER and GEPIA. The correlation between BTNL9 expression and drug response was analyzed using CARE.Results: BNL9 expression was significantly low in LUAD. Low BTNL9 expression was associated with poor OS, and its expression was found to be regulated by both epigenetic regulation and post-transcriptional modification. BTNL9 expression was significant positively correlated with ImmuneScore and ESTIMATEScore. Moreover, BTNL9 expression was positively correlated with infiltrating levels of B cells, CD4+T, and macrophages, but Kaplan-Meier analysis showed that BTNL9 expression in B cells and DCs was significantly associated with OS. Furthermore, BTNL9 expression has significant positive CARE scores. Conclusions: Low BTNL9 expression can prevent the infiltration of naïve B cells and DCs in the tumor microenvironment and worsen the outcome in LUAD patients. Besides, these findings also suggest the potential role of BTNL9 as a prognostic biomarker and a new immuno-target.