CircSCNN1A is a tumor suppressor in renal cell carcinoma via inducing the upregulation of MPP7 by the sponge effect on miR-421.

BACKGROUND: Circular RNAs (circRNAs) function as oncogenic factors or tumor repressors in variety of human malignancies. CircRNA Sodium Channel Epithelial 1 Subunit Alpha (circSCNN1A, hsa_circ_0025135) was downregulated in renal cell carcinoma (RCC). This study performed further research of circSCNN1A in RCC. METHODS: The level detection for circSCNN1A, microRNA-421 (miR-421) or Membrane Palmitoylated Protein 7 (MPP7) was conducted by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell behaviors were analyzed by Cell counting kit-8 (CCK-8) assay for cell viability, EDU assay for cell proliferation, flow cytometry for cell apoptosis, transwell assay for cell invasion and tube formation assay for angiogenesis. The protein expression was determined using western blot. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and pull-down assay were applied to validate the interaction between targets. In vivo research was performed by xenograft tumor assay. RESULTS: The level of circSCNN1A was significantly downregulated in RCC tissues and cells. RCC cell proliferation, invasion and angiogenesis were reduced but apoptosis was promoted by circSCNN1A overexpression. Interestingly, circSCNN1A could interact with miR-421. Overexpression of miR-421 has reversed the anti-tumor function of circSCNN1A in RCC cells. MPP7 served as a target of miR-421, and MPP7 inhibited the malignant phenotypes of RCC cells. In addition, miR-421 downregulation induced the inhibitory effect on the RCC development via elevating the MPP7 level. Moreover, RCC tumorigenesis was suppressed by circSCNN1A through the miR-421/MPP7 axis in vivo. CONCLUSION: The experimental data revealed that circSCNN1A upregulated the expression of MPP7 via sponging miR-421, then inhibiting the progression of RCC.

Interaction of basic diseases and low red blood cell count as critical murderer of wound infection after osteosarcoma resection: Wound infection after osteosarcoma resection.

BACKGROUND: Surgical wound infection is one of the common complications in patients after osteosarcoma resection. It is imperative to grasp the risk factors comprehensively. Therefore, this study aimed to explore the risk factors of wound infection and deeply analyze the correlation between risk factors and wound infection. METHODS: The study subjects were 101 patients who underwent osteosarcoma resection between April 2018 and August 2021. The diagnosis of postoperative wound infection was confirmed by postoperative observation of the incision, ultrasound imaging, and pathogenic examination. This study included a series of potential factors, mainly laboratory examination indicators and patients' general information. The statistical methods had Pearson Chi-square test, Spearman-rho correlation test, multifactorial linear regression model, logistic regression analysis, and receiver operating characteristic (ROC) curve. RESULTS: Pearson Chi-square test and Spearman correlation test showed that red blood cell (RBC) count (P = .033) and basic diseases (P = .020) were significantly correlated with a surgical wound infection after osteosarcoma resection. Logistic regression analysis manifested that basic disease (OR = 0.121, 95% CI: 0.015-0.960, P = .046) and RBC (OR = 0.296, 95% CI: 0.093-0.944, P = .040) have a clear correlation with whether the patients have surgical wound infection after osteosarcoma resection. And the interaction of basic diseases and RBC could diagnose the surgical wound infection sensitively and accurately (AUC = 0.700, P = .014, 95% CI = 0.564-0.836) via the ROC analysis. CONCLUSION: Patients with basic diseases and low RBC were risk factors for surgical wound infection after osteosarcoma resection.

Circular RNA circSDHC (hsa_circ_0015004) regulates tumor growth and angiogenesis via regulating centrosomal protein 55 expression in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the main aggressive subtype of kidney cancer. Circular RNAs have been shown to exert critical roles in RCC. However, little is known about the regulatory mechanism of hsa_circ_0015004 (circSDHC) in RCC. METHODS: 35 patients with RCC were recruited in the research. Expression changes of circSDHC were determined by real-time quantitative polymerase chain reaction (RT-qPCR). The effects of circSDHC inhibition on cell proliferation, apoptosis, angiogenesis, migration, and invasion were analyzed. The regulation mechanism of circSDHC was surveyed by bioinformatics analysis. The effect of circSDHC on tumorigenesis was validated by xenograft assay. RESULTS: We observed an observable elevation in circSDHC expression in RCC tissues and cell lines. Functionally, circSDHC silencing decreased xenograft tumor growth and induced RCC cell apoptosis, repressed RCC cell proliferation, angiogenesis, migration, and invasion in vitro. Mechanically, circSDHC modulated centrosomal protein 55 (CEP55) expression by functioning as a miR-130a-3p sponge. Also, miR-130a-3p silencing offset circSDHC knockdown-mediated impacts on malignant phenotypes and angiogenesis of RCC cells. Furthermore, exogenetic expression of CEP55 counteracted miR-130a-3p overexpression-mediated effects on malignant phenotypes and angiogenesis of RCC cells. CONCLUSION: Silencing of circSDHC restrained cell malignant phenotypes and angiogenesis via reducing CEP55 expression by releasing miR-130a-3p in RCC, providing a new mechanism for understanding the progression of RCC.

Higher TYROBP and lower SOX6 as predictive biomarkers for poor prognosis of clear cell renal cell carcinoma: A pilot study.

BACKGROUND: Clear cell renal carcinoma (ccRCC) is the most common subtype of renal cancer, accounting for approximately 75% of all histological types of renal cancer, and is the leading cause of death from renal cancer. However, the molecular mechanism of tyrosine kinase binding protein (TYROBP) and sex-determining region Y Box-6 (SOX6) in the ccRCC was not precise. METHODS: Bioinformatics analysis was performed to explore the hub role of TYROBP and SOX6 on the ccRCC. A total of 6 patients with clear cell renal cell carcinoma (ccRCC) were recruited. HE staining was performed to observe the pathology result of ccRCC. Immunohistochemistry and Immunofluorescence assay was made to detect the protein expression of TYROBP. Total RNA was extracted using TRIzol to examine the mRNA expression of TYROBP via the Real time quantitative polymerase chain reaction. The strong correlation between the expression of TYROBP and the survival time of ccRCC patients was performed by the BP neural network and support vector machine. RESULTS: Compared with the control group, the expression of SOX6 was downregulated in the samples with ccRCC. However, the expression of TYROBP was higher in the samples with ccRCC than in the control group. Compared with the patients with high SOX6 expression, the patients with low SOX6 expression have a poor survival prognosis (HR=0.39, P < .05). However, the patients with high TYROBP expression have a shorter survival time than the patients with low TYROBP expression (HR=1.66, P < .05). The genes related with TYROBP and SOX6 are mainly enriched in the regulation of cell activation, leukocyte activation, negative regulation of cell activation, myeloid leukocyte activation, positive regulation of response to external stimulus, immune response-regulating signaling pathway. The interaction between TYROBP, SOX6, and kidney neoplasms was drawn, and the inference score of TYROBP and SOX6 on the kidney neoplasms was high. CONCLUSION: In conclusion, TYROBP is highly expressed in renal clear cell carcinoma, and when this molecule is highly expressed, the survival prognosis of renal carcinoma is poor. TYROBP and SOX6 may be potential targets for diagnosing and treating renal clear cell carcinoma.

Silencing circular RNA circ_0054537 and upregulating microRNA-640 suppress malignant progression of renal cell carcinoma via regulating neuronal pentraxin-2 (NPTX2).

Hsa_circ_0054537 (circ_0054537) is a novel tumor-related circular RNA in renal cell carcinoma (RCC), and we intended to ascertain its dysregulation and functions in RCC malignant progression, as well as the underlying mechanism via serving as competing endogenous RNA (ceRNA). In this research, using real-time quantitative PCR, we found circ_0054537 was upregulated in RCC tissues and cells, and distributed throughout the cytoplasm. Then, functional effects of circ_0054537 in RCC were detected using cell counting kit-8, transwell, flow cytometry and glycolysis stress test and adenosine Triphosphate (ATP) assays. The results uncovered that circ_0054537 knockdown inhibited cell proliferation, migration, invasion, autophagy and glycolysis, but promoted apoptosis in RCC cells. Notably, circ_0054537 was identified as a ceRNA for microRNA (miR)-640, and miR-640 could target neuronal pentraxin-2 (NPTX2), as evidenced by dual-luciferase reporter assay and RNA immunoprecipitation assay. Besides, miR-640 downregulation or NPTX2 overexpression partly overturned the tumor suppressor function of circ_0054537 silence and miR-640 overexpression in RCC cells. Additionally, RCC cell growth in vivo was retarded by circ_0054537 silence. In conclusion, circ_0054537/miR-640/NPTX2 ceRNA pathway regulated RCC malignant progression in vitro and curbed RCC tumor growth in vivo, which could be a potential diagnosis and therapeutic target of RCC.

Identification of Key Biomarkers and Potential Molecular Mechanisms in Renal Cell Carcinoma by Bioinformatics Analysis.

Renal cell carcinoma (RCC) is the most common form of kidney cancer, caused by renal epithelial cells. RCC remains to be a challenging public health problem worldwide. Metastases that are resistant to radiotherapy and chemotherapy are the major cause of death from cancer. However, the underlying molecular mechanism regulating the metastasis of RCC is poorly known. Publicly available databases of RCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using GEO2R analysis, whereas the Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by Gene Set Enrichment Analysis (GSEA) and Metascape. Protein-protein interaction (PPI) network of DEGs was analyzed by STRING online database, and Cytoscape software was used for visualizing PPI network. Survival analysis of hub genes was conducted using GEPIA online database. The expression levels of hub genes were investigated from The Human Protein Atlas online database and GEPIA online database. Finally, the comparative toxicogenomics database (CTD; http://ctdbase.org) was used to identify hub genes associated with tumor or metastasis. We identified 229 DEGs comprising 135 downregulated genes and 94 upregulated genes. Functional analysis revealed that these DEGs were associates with cell recognition, regulation of immune, negative regulation of adaptive immune response, and other functions. And these DEGs mainly related to P53 signaling pathway, cytokine-cytokine receptor interaction, Natural killer cell mediated cytotoxicity, and other pathways are involved. Ten genes were identified as hub genes through module analyses in the PPI network. Finally, survival analysis of 10 hub genes was conducted, which showed that the MMP2 (matrix metallo peptidase 2), DCN, COL4A1, CASR (calcium sensing receptor), GPR4 (G protein-coupled receptor 4), UTS2 (urotensin 2), and LDLR (low density lipoprotein receptor) genes were significant for survival. In this study, the DEGs between RCC and metastatic RCC were analyzed, which assist us in systematically understanding the pathogeny underlying metastasis of RCC. The MMP2, DCN, COL4A1, CASR, GPR4, UTS2, and LDLR genes might be used as potential targets to improve diagnosis and immunotherapy biomarkers for RCC.