Renal Cancer Cell Proliferation Research Articles

MiR-4429 inhibits ccRCC proliferation, migration, and invasion by directly targeting CD274

Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive urological malignancies and a highly immunogenic cancer. Yet, its pathogenesis is still not fully understood. This study analyzed the role of the miR-320 family in ccRCC using bioinformatics algorithms and a series of in vitro experiments. miR-4429 was found to be significantly down-regulated in ccRCC tissues and cell lines, while overexpression of miR-4429 significantly inhibited renal cancer cell proliferation, migration, and invasion in vitro. In addition, the UALCAN database, immunohistochemistry, and protein blotting results showed that CD274 expression was up-regulated in ccRCC tissues and correlated with higher histologic grading. Dual luciferase assay indicated that CD274 was a direct target of miR-4429. Overexpression of miR-4429 in 786-O, Caki-2 cells significantly inhibited CD274 expression. KEGG results indicated that the potential target function of miR-4429 was associated with the PI3K/AKT signaling pathway, and protein blotting verified the results. In summary, this data shows that miR-4429 targets CD274 and inhibits ccRCC proliferation, migration, and invasion by regulating PI3K/AKT signaling, thus potentially providing a promising therapeutic target and prognostic biomarker for renal cell carcinoma patients.Graphical

Multi-omics and immunogenomics analysis revealed PFKFB3 as a targetable hallmark and mediates sunitinib resistance in papillary renal cell carcinoma: in silico study with laboratory verification

Glycolysis-related metabolic reprogramming is a central hallmark of human cancers, especially in renal cell carcinoma. However, the regulatory function of glycolytic signature in papillary RCC has not been well elucidated. In the present study, the glycolysis-immune predictive signature was constructed and validated using WGCNA, glycolysis-immune clustering analysis. PPI network of DEGs was constructed and visualized. Functional enrichments and patients’ overall survival were analyzed. QRT-PCR experiments were performed to detect hub genes’ expression and distribution, siRNA technology was used to silence targeted genes; cell proliferation and migration assays were applied to evaluate the biological function. Glucose concentration, lactate secretion, and ATP production were measured. Glycolysis-Immune Related Prognostic Index (GIRPI) was constructed and combined analyzed with single-cell RNA-seq. High-GIRPI signature predicted significantly poorer outcomes and relevant clinical features of pRCC patients. Moreover, GIRPI also participated in several pathways, which affected tumor immune microenvironment and provided potential therapeutic strategy. As a key glycolysis regulator, PFKFB3 could promote renal cancer cell proliferation and migration in vitro. Blocking of PFKFB3 by selective inhibitor PFK-015 or glycolytic inhibitor 2-DG significantly restrained renal cancer cells’ neoplastic potential. PFK-015 and sunitinib could synergistically inhibit pRCC cells proliferation. Glycolysis-Immune Risk Signature is closely associated with pRCC prognosis, progression, immune infiltration, and therapeutic response. PFKFB3 may serve as a pivotal glycolysis regulator and mediates Sunitinib resistance in pRCC patients.

GALNT2 targeted by miR-139-5p promotes proliferation of clear cell renal cell carcinoma via inhibition of LATS2 activation

Polypeptide N-Acetylgalactosaminyltransferase (GALNTs) are critical enzymes that initiate mucin type-O glycosylation, and are closely associated with the occurrence and development of multiple cancers. However, the significance of GALNT2 in clear cell renal cell carcinoma (ccRCC) progression remains largely undetermined. Based on public multi-omics analysis, GALNT2 was strongly elevated in ccRCC versus adjoining nontumor tissues, and it displayed a relationship with poor overall survival (OS) of ccRCC patients. In addition, GALNT2 over-expression accelerated proliferation of renal cancer cell (RCC) lines. In contrast, GALNT2 knockdown using shRNAs suppressed cell proliferation, and this was rescued by LATS2 knockdown. Similarly, GALNT2 deficiency enhanced p-LATS2/LATS2 expression. LATS2 is activated by phosphorylation (p-LATS2) and, in turn, phosphorylate the downstream substrate protein YAP. Phosphorylated YAP (p-YAP) stimulated its degradation and cytoplasmic retention, as it was unable to translocate to the nucleus. This resulted in reduced cell proliferation. Subsequently, we explored the upstream miRNAs of GALNT2. Using dual luciferase reporter assay, we revealed that miR-139-5p interacted with the 3ʹ UTR of GALNT2. Low miR-139-5p expression was associated with worse ccRCC patient outcome. Based on our experiments, miR-139-5p overexpression inhibited RCC proliferation, and this phenotype was rescued by GALNT2 overexpression. Given these evidences, the miR-139-5p-GALNT2-LATS2 axis is critical for RCC proliferation, and it is an excellent candidate for a new therapeutic target in ccRCC.

Total polyphenols of Cydonia oblonga inhibited proliferation and migration of renal cancer cells by PI3K/Akt/mTOR pathway

The mechanism of total polyphenols of Cydonia oblonga Miller(TPCOM) against kidney cancer was elucidated through a combination of network pharmacology, bioinformatics, and experimental verification. The active polyphenolic compounds from C. oblonga were screened by network pharmacological techniques and kidney cancer-related targets were collected through the database. The differential gene expression analysis was performed on RNA sequencing data from tumor tissue and normal tissue of kidney cancer patients obtained from the Gene Expression Omnibus(GEO) database. The results of network pharmacology predictions and differential gene expression analysis were used to identify the core genes targeted by TPCOM in kidney cancer. Survival analysis was conducted to identify key targets that could impact patient survival, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) enrichment analyses. Cell proliferation and activity experiments(cell counting kit-8) were conducted using TPCOM at concentrations ranging from 20 to 640 μg·mL~(-1) on 786-O and Renca cells. Additionally, TPCOM at concentrations of 40, 80, and 160 μg·mL~(-1) was applied to kidney cancer cells to assess its effect on cell migration and its regulation of protein expression levels related to the protein kinase B(Akt), mammalian target of rapamycin(mTOR), and phosphoinositide 3-kinase(PI3K) signaling pathways. Network pharmacology predicted eight active polyphenolic compounds from C. oblonga. Survival analysis revealed 15 significantly differentially expressed genes in kidney cancer that were affected by TPCOM and had a significant impact on patient survival. KEGG and GO analysis results indicated that these 15 targets were primarily associated with the PI3K/Akt signaling pathway, cell migration, and proliferation. The results showed that TPCOM could inhibit the proliferation of 786-O and Renca cells, with IC_(50) values of 121.4 and 137.9 μg·mL~(-1), respectively. TPCOM was also found to inhibit the migration of these cells and suppress the PI3K/Akt/mTOR signaling pathway. TPCOM may exert its anti-kidney cancer effects by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway, thereby restraining the proliferation and migration of kidney cancer cells. This study provides a foundation for the research on the anti-tumor effects of natural product C. oblonga, particularly in Xinjiang, and holds significance for further promoting its development and utilization.

Coiled-coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK-NF-κB signaling pathway.

Increasing evidence has demonstrated that the expression of coil domains containing 25 (CCDC25) in various malignancies is abnormally high. However, the potential regulatory role and mechanism of CCDC25 in the development of clear cell renal cell carcinoma (ccRCC) are still unclear. In this experiment, we combined invitro experiments such as wound healing, CCK8, and transwell assay with invivo experiments on tumor formation in nude mice to evaluate the effect of CCDC25 on the proliferation, migration, and invasion of renal cancer cells. In addition, we also used Western blotting and qPCR to evaluate the role of CCDC25 in activating the integrin-linked kinase (ILK)-NF-κB signaling pathway. Here, we demonstrate that compared to normal tissues and cell lines, CCDC25 is overexpressed in both human ccRCC tissues and cell lines. After CCDC25 knockdown, it has obvious inhibitory effect on the proliferation, migration, and invasion of cancer cells invitro and invivo. In contrast, CCDC25 overexpression promotes these effects. Additionally, we also discovered that CCDC25 interacts with ILK and coordinates the activation of the NF-κB signaling pathway downstream. Generally, our study suggests that CCDC25 plays a vital role in the development of ccRCC, which also means that it may be a potential therapeutic target for ccRCC.

FOXA2 activates HIF2α expression to promote tumor progression and is regulated by the E3 ubiquitin ligase VHL in renal cell carcinoma

Renal cell carcinoma (RCC) is a frequent malignancy of the urinary system with high mortality and morbidity. However, the molecular mechanisms underlying RCC progression are still largely unknown. In this study, we identified FOXA2, a pioneer transcription factor, as a driver oncogene for RCC. We show that FOXA2 was commonly upregulated in human RCC samples and promoted renal cancer cell proliferation, as evidenced by assays of cell viability, colony formation, migratory and invasive capabilities, and stemness properties. Mechanistically, we found that FOXA2 promoted RCC cell proliferation by transcriptionally activating HIF2α expression in vitro and in vivo. Furthermore, we found that FOXA2 could interact with VHL (von Hippel‒Lindau), which ubiquitinated FOXA2 and controlled its protein stability in RCC cells. We showed that mutation of lysine at position 264 to arginine in FOXA2 could mostly abrogate its ubiquitination, augment its activation effect on HIF2α expression, and promote renal cancer cell proliferation in vitro and RCC progression in vivo. Importantly, elevated expression of FOXA2 in RCC patients positively correlated with the expression of HIF2α and was associated with shorter overall and disease-free survival. Together, these findings reveal a novel role of FOXA2 in RCC development and provide insights into the underlying molecular mechanisms of FOXA2-driven pathological processes in RCC.

Dysregulated ANLN reveals immune cell landscape and promotes carcinogenesis by regulating the PI3K/Akt/mTOR pathway in clear cell renal cell carcinoma

BackgroundAbnormal anillin (ANLN) expression has been observed in multiple tumours and is closely associated with patient prognosis and clinical features. In this study, we systematically elucidated the clinical significance and biological roles of ANLN in patients with clear cell renal cell carcinoma (ccRCC). MethodsWe obtained transcriptome and clinical data of patients with ccRCC from public databases. Multi-omics data and clinical samples were combined to analyse the correlation between ANLN expression and the clinical characteristics of patients with renal cancer. Additionally, the immune cell landscape of ANLN expression was evaluated using different immune algorithms in the tumour microenvironment. The tumour-promoting potential of ANLN was confirmed using in vitro assays, including CCK8 and Transwell assays. ResultsBioinformatics analysis showed that ANLN is over-expressed in patients with ccRCC, as validated by clinical samples. Publicly available clinical data suggest that high ANLN expression may indicate poor outcomes in patients with ccRCC. Moreover, biological function analysis revealed a marked enrichment of the cell cycle and PI3K-Akt pathways. The distribution of immune cells, particularly M2 macrophages, differed in patients with ccRCC. Furthermore, ANLN silencing inhibited the proliferation, migration, and invasion of renal cancer cells in vitro. After ANLN expression was knocked down in 786-O cells, the protein levels of important PI3K signalling pathway components, including PI3K, Akt, and mTOR, drastically decreased. ConclusionsThese findings suggest that ANLN is dysregulated in renal cancer tissues and promotes tumour progression by activating the PI3K/Akt/mTOR signalling pathway.

PLAC8 is an innovative biomarker for immunotherapy participating in remodeling the immune microenvironment of renal clear cell carcinoma.

PLAC8 has been identified in the progression of various cancers by inducing tumorigenesis, immune response, chemotherapy resistance and metastasis. Nevertheless, the precise biological function of PLAC8 in renal cancer remains unknown. We obtained the expression profile and associated clinical characteristics of patients diagnosed with clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas database. The biological behavior of specific cell lines was detected using Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assay. A prognostic model was constructed based on PLAC8-related molecules through a machine-learning algorithm. We observed overexpression of PLAC8 in ccRCC patients. In addition, PLAC8 has been identified as being linked to unfavorable clinical characteristics and adverse prognosis outcomes. Biological enrichment analysis revealed the potential involvement of PLAC8 in cell cycle checkpoints, mitotic phase transformation, immunotherapy-predicted and reactive oxygen species (ROS) related pathways. In addition, immune analyses showed that PLAC8 was involved in remodeling the tumor microenvironment (TME) and affecting the effect of immunotherapy in ccRCC patients. In vitro experiments demonstrated a significant reduction in the proliferation, invasion and migration of renal cancer cells following the knockdown of PLAC8. Finally, LASSO logistics regression was applied to construct a prognosis model, which presented a favorable prediction ability on the prognosis of ccRCC. Our results implied that PLAC8 may be a novel immunotherapy biomarker of ccRCC, which is a crucial molecule in remodeling the cancer microenvironment. PLAC8 can predict immunotherapy response and is expected to guide precise treatment.

Three as-synthesized silver nanowires (Ag NWs) with different size on renal cancer treatment

In this paper, three as synthesized silver nanowires (Ag NWs 1–3) have been successfully synthesized via the one-step polyol synthesis at 150 °C for 8 h, which use the NaCl, ZnCl2 and CuCl2 as the inorganic control agents to control the size and length of the Ag NWs. Three Ag NWs sample have been characterized by the scanning electron microscope (SEM) and powder X-ray diffraction (PXRD). The novel Ag NWs application on anti-renal cancer was explored and the specific mechanism was determined simultaneously. The results suggested that Ag NWs inhibited renal cancer by decreasing renal cancer cell proliferation and up-regulating SUCLG1 and PCK2 expression. The Ag NWs showed the potential to be developed as the anti-tumor drug.

Better prediction of clinical outcome in clear cell renal cell carcinoma based on a 6 metabolism-related gene signature

It has been reported that metabolic disorders participate in the formation and progression of clear cell renal cell carcinoma (ccRCC). However, the predictive value of metabolism-related genes (MRGs) in clinical outcome of ccRCC is still largely unknown. Herein, a novel metabolism-related signature was generated to assess the effect of MRGs on the prognosis of ccRCC patients. Important module MRGs were selected by differentially expressed analysis and WGCNA. Subsequently, the hub MRGs were screened via univariate cox regression as well as LASSO regression. A new metabolism-related signature of 6 hub MRGs (PAFAH2, ACADSB, ACADM, HADH, PYCR1 and ITPKA) was constructed, with a good prognostic prediction ability in the TCGA cohort. The prediction accuracy of this signature was further confirmed in both GSE22541 and FAHWMU cohort. Interestingly, this MRG risk signature was highly correlated with tumor mutation burden and immune infiltration in ccRCC. Notably, lower PAFAH2, a member of 6 MRGs, was found in ccRCC. Knockdown of PAFAH2 contributed to renal cancer cell proliferation and migration. Collectively, a 6-MRG prognostic risk signature is generated to estimate the prognostic status of ccRCC patients, providing a novel insight in the prognosis prediction and treatment of ccRCC.

Ursolic Acid against Prostate and Urogenital Cancers: A Review of In Vitro and In Vivo Studies.

Prostate cancer is the second most diagnosed form of cancer in men worldwide and accounted for roughly 1.3 million cases and 359,000 deaths globally in 2018, despite all the available treatment strategies including surgery, radiotherapy, and chemotherapy. Finding novel approaches to prevent and treat prostate and other urogenital cancers effectively is of major importance. Chemicals derived from plants, such as docetaxel and paclitaxel, have been used in cancer treatment, and in recent years, research interest has focused on finding other plant-derived chemicals that can be used in the fight against cancer. Ursolic acid, found in high concentrations in cranberries, is a pentacyclic triterpenoid compound demonstrated to have anti-inflammatory, antioxidant, and anticancer properties. In the present review, we summarize the research studies examining the effects of ursolic acid and its derivatives against prostate and other urogenital cancers. Collectively, the existing data indicate that ursolic acid inhibits human prostate, renal, bladder, and testicular cancer cell proliferation and induces apoptosis. A limited number of studies have shown significant reduction in tumor volume in animals xenografted with human prostate cancer cells and treated with ursolic acid. More animal studies and human clinical studies are required to examine the potential of ursolic acid to inhibit prostate and other urogenital cancers in vivo.

SLC14A1 is a new biomarker in renal cancer.

Renal cancer is one of the common malignant tumors of the urinary tract, prone to distant metastasis and drug resistance, with a poor clinical prognosis. SLC14A1 belongs to the solute transporter family, which plays a role in urinary concentration and urea nitrogen recycling in the renal, and is closely associated with the development of a variety of tumors. Transcription data for renal clear cell carcinoma (KIRC) were obtained from the public databases Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA), and we investigated the differences in SLC14A1 expression in cancerous and normal tissues of renal cancer, its correlation with the clinicopathological features of renal cancer patients. Then, we verified the expression levels of SLC14A1 in renal cancer tissues and their Paracancerous tissues using RT-PCR, Western-blotting and immunohistochemistry. Finally, we used renal endothelial cell line HEK-293 and renal cancer cell lines 786-O and ACHN to explore the effects of SLC14A1 on the biological behaviors of renal cancer cell proliferation, invasion and metastasis using EDU, MTT proliferation assay, Transwell invasion assay and scratch healing assay. SLC14A1 was lowly expressed in renal cancer tissues and this was further validated by RT-PCR, Western blotting, and immunohistochemistry in our clinical samples. Analysis of KIRC single-cell data suggested that SLC14A1 was mainly expressed in endothelial cells. Survival analysis showed that low levels of SLC14A1 expression were associated with a better clinical prognosis. In biological behavioral studies, we found that upregulation of SLC14A1 expression levels inhibited the proliferation, invasion, and metastatic ability of renal cancer cells. SLC14A1 plays an important role in the progression of renal cancer and has the potential to become a new biomarker for renal cancer.

Licochalcone A Suppresses Renal Cancer Cell Proliferation and Metastasis by Engagement of Sp1-Mediated LC3 Expression

Licochalcone A (LicA) is a strong anti-inflammatory, antioxidant, and anticarcinogenic substance that is useful against a variety of human malignancies. However, its precise mechanism in mediating the development of renal cell carcinoma (RCC) is not entirely understood. In this work, LicA was discovered to limit cell growth and survival, induce cell cycle arrest, promote autophagy and LC3B expression, and inhibit the migration and invasion of RCC cells. In addition, the proliferation, migration, and invasion inhibited by LicA were restored by the transfection of siRNA-LC3. The effects of LC3B on the metastatic phenotype of ACHN cells was enhanced with the overexpression of Sp1 or suppressed by inhibiting the phosphorylation of FAK and Src. Finally, LicA showed antitumor properties against RCC in an in vivo xenograft model. In conclusion, our study demonstrated the chemotherapeutic potential of LicA on proliferation, migration, invasion, and autophagy through the activation of LC3B expression, ultimately modulating FAK/Src signaling pathway-mediated Sp1 expression. These findings illustrate the novel role and molecular mechanisms of LicA against RCC cells.

SLC17A9-PTHLH-EMT axis promotes proliferation and invasion of clear renal cell carcinoma

SLC17A9 is a vesicular ATP transport protein that plays an important role in determining cell functions and the onset and progression of different diseases. In this study, SLC17A9 was initially identified as a potential diagnostic and prognostic risk biomarker for clear cell renal cell carcinoma (ccRCC). Then, the aberrant expression levels of SLC17A9 were confirmed in both the cell lines and clinical tissues. Mechanistically, SLC17A9 could upregulate the expression of PTHLH, thus promoting epithelial-mesenchymal transition (EMT) in ccRCC. Functionally, SLC17A9 knockdown inhibited the proliferation, migration, and invasion activity of renal cancer cells, whereas its overexpression led to stronger cell viability and more malignant phenotype invitro. The overexpression of SLC17A9 invivo could significantly contribute to the growth of tumors. Finally, we found that SLC17A9 might be related to the drug resistance of vorinostat. Cumulatively, this study demonstrated that the SLC17A9-PTHLH-EMT axis could promote the progression of ccRCC.

Dry and wet experiments reveal the significant role of FUT11 in clear cell renal cell carcinoma.

Renal cancer is one of the most common urogenital tumors worldwide. Although numerous traditional and relatively new therapeutic strategies have been adopted for clear cell renal cell carcinoma (ccRCC) patients, their effects are not satisfactory enough for the improvement of patients. The pathogenesis and progression of ccRCC requires further investigations. Using a series of bioinformatic analyses, the expression levels, clinical relevance, and prognostic potential of FUT11 as well as its correlations with immune cells in ccRCC were investigated. The mRNA and protein expression levels of FUT11 in renal cancer cell lines and human tissues were determined using quantitative real-time-polymerase chain reaction (RT-PCR) and Western blot analyses. MTT, colony formation, Edu, and wound healing assays were performed to explore the function of FUT11 in renal cancer cell lines. The immunohistochemical staining of human and mouse tissues was performed to reveal the correlations between the expression levels of FUT11 and the infiltration level of immune cell subtypes. Using mouse xenograft models, the role of FUT11 was further investigated in-vivo. The data mining and corresponding analyses indicated that the expression levels of FUT11 were elevated in renal cancer and independently correlated with the prognosis of ccRCC patients. The cibersort and ssGSEA algorithms revealed differential infiltration levels of immune cells between the patients with distinct expression levels of FUT11; these results were verified by the consequent human renal cancer tissues and animal models. The MTT, colony formation, EdU, and wound healing assays showed that the decreased expression level of FUT11 could promote the proliferation and migration of renal cancer cell lines. The animal models-based analysis showed similar results. In conclusion, this study identified a novel important molecule correlated with the prognosis of ccRCC patients and revealed its immune-related role and its function in the proliferation and migration of renal cancer cells. This study might provide a novel basis for the treatment of renal cancer.

The roles of long non‑coding RNAs in renal cell carcinoma (Review).

Long non-coding RNAs (lncRNAs) are involved in the gene expression regulation and usually play important roles in various human cancers, including the renal cell carcinoma (RCC). Dysregulation of certain lncRNAs are associated with the prognosis of patients with RCC. In the present review, several recently studied lncRNAs were discussed and their critical roles in proliferation, migration, invasion, apoptosis and drug resistance of renal cancer cells were revealed. The research on lncRNAs further increases our understanding on the development and progression of RCC. It is suggested that lncRNAs can be used as biomarkers or therapeutic targets for diagnosis or treatment of renal cancer.

Sustained release system of paclitaxel based on composite nanofibers for inhibiting renal clear cell carcinoma

The recurrence and metastasis of renal cell carcinoma are severe challenges in clinical treatment. At present, it is urgent to find a strategy to solve this problem and improve the therapeutic effect. In this study, we designed a programmed release system of anticancer drugs by preparing a nanofiber system with two kinds of diameters and biomaterials (polylactic acid-glycolic acid (PLGA) and silk protein) as drug carriers (paclitaxel), which inspired the occurrence and pathological microenvironment of renal cell carcinoma. The controlled degradation of PLGA nanofibers as a drug carrier achieved the short-term release of paclitaxel, which could rapidly inhibit the spread and metastasis of renal cancer, while the silk protein nanofibers as a drug carrier with slow degradation could provide the long time and continuous release of paclitaxel to prevent the proliferation of renal cancer cells and inhibit recurrence. The synergistic effect of the sustained release system of paclitaxel successfully achieved inhibition of the recurrence and metastasis of renal cell carcinoma and improve the therapeutic effect of renal cell carcinoma. The paclitaxel release profile showed that the PLGA nanofiber drug system provided controlled release of paclitaxel in the first 14 days, while the silk protein nanofiber system provided a relatively stable and long-duration release of paclitaxel (1 month). In vitro experiments showed that the sustained release system of paclitaxel had a lasting inhibitory effect on the proliferation of renal clear cell carcinoma cells. These results indicated that the sustained release system of paclitaxel could be used as a promising drug delivery system with highly efficient implementations to reduce the frequency of systemic administration and inhibit tumor growth and recurrence, which could provide a new strategy for the clinical applications in renal cell carcinoma microenvironment.

Calbindin S100A16 Promotes Renal Cell Carcinoma Progression and Angiogenesis via the VEGF/VEGFR2 Signaling Pathway.

Purpose Recent research has indicated that the calcium-binding protein S100A16 promotes carcinogenesis and tumor growth in several forms of cancer. The objective of this study was to examine the relationship between S100A16 and renal cell cancer. Methods By using The Cancer Genome Atlas (TCGA) database, the differentially expressed gene S100A16 was identified, and its appearance and link to the prognosis of persons with renal cancer were confirmed. Cox regression was used in multivariate analysis, and a nomogram was developed for internal validation. The correlation between S100A16 and immune cells was analyzed in the TIMER database. Moreover, the potential mechanism of action was investigated utilizing GO and KEGG enrichment analyses. Proliferation, migration, and angiogenesis were investigated in vitro, and the involvement of S100A16 in the undesirable biological events of renal cell carcinoma (RCC) was further explored. Results S100A16 was the differentially expressed molecule identified through database screening. Malignant tissues showed higher S100A16 expression than noncancerous tissues, and S100A16 expression was mostly localized in the cytoplasm. According to the TCGA and KM-plotter datasets, patients with RCC and low S100A16 expression had superior OS, PFI, and DSS. The C-index of the nomogram was 0.754 (0.726–0.782), and the accuracy of the prediction model was high. The TIMER database shows that the expression of S100A16 is associated with immune infiltration and may play an important role in promoting tumor cell immune escape in the RCC tumor microenvironment. S100A16 may influence the biological processes of RCC via the VEGF/VEGFR2 signaling route and PI3K-Akt signaling pathway and through P53 alteration and cell cycle according to the gene enrichment technique. In vitro cytological experiments demonstrated that S100A16 knockdown can inhibit the proliferation and migration of renal cancer cells and the expression levels of VEGF, VEGFR2, and phosphorylated AKT within renal cancer cells, thereby inhibiting angiogenesis in renal cancer cells and resulting in a poor prognosis of RCC. Conclusion A decrease in S100A16 expression may dramatically increase the OS, PFI, and DSS of patients with RCC and may thus be used as a biomarker for predicting RCC. It may be associated with the immune infiltration of RCC and play a crucial role in the immune evasion of tumor cells within the RCC microenvironment. Intervention of s100a16 can promote the progression and angiogenesis of renal cell carcinoma through the VEGF/VEGFR2 signal transduction pathway and lead to poor prognosis of renal cell carcinoma. These findings suggest a potential target for the development of anticancer strategies for renal cancer.

MiR-5590-3p inhibits the proliferation and metastasis of renal cancer cells by targeting ROCK2 to inhibit proliferation, migration and invasion.

The present study aimed to clarify the role of microRNA (miR)-5590-3p in the progression of renal cell carcinoma (RCC) and investigate the underlying mechanisms. The expression levels of miR-5590-3p, Rho-associated protein kinase (ROCK)2 and β-catenin in RCC cells were measured by reverse transcription-quantitative PCR and western blot analysis. Following overexpression of miR-5590-3p and ROCK2 by transfection of miR-5590-3p mimics and GV367-ROCK2, respectively, changes in the proliferation, migration and invasion of RCC cells were determined through colony-formation, wound-healing and Transwell assays, respectively. The direct binding interaction between miR-5590-3p and ROCK2, initially predicted using Targetscan, was validated by a dual-luciferase reporter assay. The results indicated that miR-5590-3p was downregulated in RCC. Overexpression of miR-5590-3p led to downregulation of ROCK2 and β-catenin and inhibited the proliferation, migration and invasion of RCC cells. The dual-luciferase reporter assay confirmed the binding relationship between miR-5590-3p and ROCK2. Of note, overexpression of ROCK2 effectively reversed the regulatory effects of miR-5590-3p on RCC cells. In conclusion, miR-5590-3p inhibits the proliferation, migration and invasion of RCC cells by targeting ROCK2, which is a potential molecular biomarker and therapeutic target for RCC.

Sodium selenite inhibits proliferation and metastasis through ROS‐mediated NF‐κB signaling in renal cell carcinoma

BackgroundSodium selenite (SSE) has been reported to exert anti-tumor effects in several cancer cells. However, the underlying mechanisms in renal cancer are yet to be elucidated. The effects of SSE on the proliferation, metastasis, and apoptosis of renal cancer cells, as well as its mechanism, were investigated in this study.MethodsACHN and 786-O renal cancer cells were treated with different concentrations of SSE, MTT, and colony formation assays were used to detect the proliferation ability of cells. The migration of cells was detected using scratch-wound-healing and transwell-migration assays. The effect of SSE on apoptosis was assessed by AnnexinV-FITC/PI double staining. Besides, Western blotting was employed to detect the protein-expression level and elucidate the underlying pathways. We also made subcutaneous xenografts in athymic mice to verify the effect of SSE on tumor growth in vivo.ResultsOur results demonstrated that treatment with SSE resulted in significant inhibition of cell proliferation and migration. Flow cytometry and Western blot confirmed that SSE induced apoptosis via the endogenous apoptotic pathway. We also confirmed that SSE treatment causes an increase in intracellular reactive oxygen species (ROS) levels, resulting in the inhibition of nuclear transcription factor-κB (NF-κB) signaling. Modulation of the ROS level by the chemical inhibitor N-acetyl-cysteine reversed the effect of SSE on cells. Similarly, subcutaneous xenografts in athymic mice models showed that SSE inhibits tumor growth in vivo. ConclusionThese results indicate that SSE inhibits proliferation and migration and induces apoptosis via ROS mediated inhibition of NF-κB signaling in renal cancer cells.