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Purpose: To explore the biological functions and mechanism of Opa interacting protein 5 (OIP5) in bladder cancer (BC). Methods: We investigated the expression of OIP5 in BC through immunohistochemical staining (IHC) and its correlation with clinicopathologic features of BC patients. Moreover, knockdown of OIP5 was performed in BC cell lines and colony formation capacity, cell growth curve, cell cycle phase and cell apoptosis assay was applied for investigating the roles of OIP5 in BC. Moreover, the expression of OIP5 was validated through the Cancer Genome Atlas (TCGA) database. The diagnosis value of OIP5 was accessed by receiver operating characteristic (ROC) analysis in TCGA database. Results: The expression of OIP5 in BC tissues was significantly higher than that in adjacent non-tumor tissues and bladder mucosa tissues with chronic cystitis. Higher protein expression level of OIP5 predicted shorter survival time in patients with BC, which was significantly correlated with larger tumor size, high-grade tumor and advanced T classification. The expression of OIP5 was considerably decreased after lentivirus infection both at mRNA and protein levels. Functional assay displayed that silencing of OIP5 inhibited colony formation capacity and cell growth in BC cell lines. Cell cycle assays indicated that suppressed OIP5 disturbed the balance of the cell cycle in BC cell lines, which increased the cell population of the G1 phase and decreased the cell population of the S phase. Furthermore, knockdown of OIP5 expression enhanced cell apoptosis process. The expression of OIP5 was significantly up-regulated in BC compared with adjacent non-tumor tissues based on TCGA database. OIP5 had the potential diagnostic value for BC. Conclusions: Our work demonstrated that OIP5 might function as an oncogene to promote colony formation capacity and cell growth, arrest cell cycle and suppress cell apoptosis in bladder cancer. [ABSTRACT FROM AUTHOR]

Objectives In our previous study, we displayed that knockdown of Opa interacting protein 5 (OIP5 ) inhibited cell growth, disturbed cell cycle and increased cell apoptosis in bladder cancer (BC) cell line. Our present study aimed to explore the underlying pathways and interaction network involved in the roles of OIP5 in BC. Methods Microarray analysis was conducted to obtain mRNA expression profiling of OIP5 knockdown (shOIP5) and control (shCtrl) BC cell lines. Bioinformatics analyses were performed including differentially expressed mRNAs (DEGs) identification, protein-protein interaction network construction, biological functions of prediction and ingenuity pathways analysis (IPA). Western Blotting (WB) was subjected to validate the protein expression levels of candidate DEGs in shOIP5 BC cell line. Results Respective 255 up- and 184 down-regulated DEGs were identified in shOIP5 group compared with shCtrl group. In the PPI network, CAND1 and MYC had the highest connectivity with DEGs. 439 DEGs were significantly enriched in inflammatory response, regulation of cell proliferation, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction and bladder cancer. In the disease and function enrichment, DEGs were obviously involved in cellular movement, cellular growth and proliferation, cancer, inflammatory response, cell death and survival. In the OIP5 regulatory network, CDH2, IRS1, IRAK3, ID1, TNF, IL6, ITGA6, MYC and SOD2 interacted with OIP5. The WB validation results were compatible with our bioinformatics analyses. Conclusions OIP5 interaction network might function as an oncogene in BC progression based on aberrant inflammatory responses. Our study might provide valuable information for investigation of tumorigenesis mechanism in BC. [ABSTRACT FROM AUTHOR]

Background: Skin cutaneous melanoma (SKCM) is the most aggressive skin cancer, accounting for more than 75% mortality rate of skin-related cancers. As a newly identified programmed cell death, pyroptosis has been found to be closely associated with tumor progression. Nevertheless, the prognostic significance of pyroptosis in SKCM remains elusive. Methods: A total of 469 SKCM samples and 812 normal samples were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Firstly, differentially expressed pyroptosis-related genes (PRGs) between normal samples and SKCM samples were identified. Secondly, we established a prognostic model based on univariate Cox and LASSO Cox regression analyses, which was validated in the test cohort from GSE65904. Thirdly, a nomogram was used to predict the survival probability of SKCM patients. The R package "pRRophetic" was utilized to identify the drug sensitivity between the low- and high-risk groups. Tumor immune infiltration was evaluated using "immuneeconv" R package. Finally, the function of GSDMD and SB525334 was explored in A375 and A2058 cells. Results: Based on univariate Cox and LASSO regression analyses, we established a prognostic model with identified eight PRGs (AIM2, CASP3, GSDMA, GSDMC, GSDMD, IL18, NLRP3, and NOD2), which was validated in the test cohort. SKCM patients were divided into low- and high-risk groups based on the median of risk score. Kaplan–Meier survival analysis showed that high-risk patients had shorter overall survival than low-risk patients. Additionally, time-dependent ROC curves validated the accuracy of the risk model in predicting the prognosis of SKCM. More importantly, 4 small molecular compounds (SB525334, SR8278, Gemcitabine, AT13387) were identified, which might be potential drugs for patients in different risk groups. Finally, overexpression of GSDMD and SB525334 treatment inhibit the proliferation, migration, and invasion of SKCM cells. Conclusion: In this study, we constructed a prognostic model based on PRGs and identified GSDMD as a potential therapeutic target, which provide new insights into SKCM treatment. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) has been regarded as one of the most malignant tumor types. Chemotherapy (such as sorafenib) is used as common strategy for treating RCC. To date, whether long noncoding RNA KIF9-AS1 is involved in RCC progression and drug resistance remains unknown. In this investigation, we detected gene expression levels by western blot and RT-qPCR. MTT and TUNEL experiments were used to show cell viability and apoptosis, respectively. KIF9-AS1 overexpression led to enhanced cell viability, increased IC50 value of sorafenib, and decreased apoptosis. miR-497-5p acted as key interaction factor for KIF9-AS1 in RCC. More importantly, we found that transforming growth factor-β and autophagy signaling pathways were both critical effectors for mediating KIF9-AS1/miR-497-5p axis-induced drug resistance phenotypes (cell viability, IC50, apoptosis) of RCC. In conclusion, our study revealed that KIF9-AS1 played a positive role in drug resistance of RCC cells to sorafenib, potentially driving the development of targeted diagnostic and therapeutical approaches. [ABSTRACT FROM AUTHOR]