Renal Cell Carcinoma Migration Research Articles

The role of cyclin-dependent kinase inhibitor 3 in the proliferation and migration of renal cell carcinoma

The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, is over expressed in renal cell carcinoma (RCC). However, the cell biology functions of RCC are not well understood. The present study aimed to verify the ability of CDKN3 to promote the proliferation and migration of RCC through in vitro experiments. Subsequently, the clinical prognostic effects were analyzed using The Cancer Genome Atlas (TCGA; https://www.cancer.gov/) and Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/). The chelators, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), an analogue of the anti-tumor agent, were screened through bioinformatics analysis. The expression of CDKN3 is positively correlated with the IC50 of Dp44mT. In two RCC cell lines, 786-0 and Caki-1, we conducted small interfering RNA (siRNA) knockdown of CDKN3 and overexpression of CDKN3 by transfection plasmid. Subsequently, we administered Dp44mT to examine the resulting alterations in cell proliferation, migration, and apoptosis, thereby elucidating the role of CDKN3 and Dp44mT in these processes. The results of the experiment revealed a positive association between CDKN3 expression and the proliferation of RCC cell lines. Down-regulating CDKN3 significantly increased the apoptosis rate and inhibited cell migration in 786-0 and Caki-1 cells. Furthermore, bioinformatics analysis revealed a high expression of CDKN3 in RCC and a negative association between CDKN3 expression and survival. Gene set enrichment analysis (GSEA) revealed a significant association between high CDKN3 expression and the cell cycle pathway. Furthermore, we identified Dp44mT as a drug highly correlated with CDKN3 through the database. Subsequent addition of Dp44mT resulted in similar findings to those observed upon CDKN3 knockdown. Our findings have important implications for the diagnosis and treatment of CDKN3 in RCC. Additionally, Dp44mT is likely to be a promising candidate for future clinical applications.

Poria acid inhibit the growth and metastasis of renal cell carcinoma by inhibiting the PI3K/akt/NF-κb signaling pathway

BackgroundPoria acid (PAC) is a triterpene compound found in Poria cocos, a traditional Chinese medicine (TCM). The current study aims to explore the therapeutic effects and potential mechanisms of PAC on the migration and proliferation of human renal cell carcinoma (RCC) cells as well as tumor growth in animal model. MethodsCell viability and proliferative capacity of normal renal cells and RCC cells were investigated by MTT assay. In addition, 786-O cells were divided into four groups and treated with different concentrations of PAC (0, 20, 40, and 60 μM) for 48 h. Cell scratch test and cell invasion assay were performed to evaluate the effects of PAC on the invasion and migration of RCC cells, respectively. The effects of PAC on apoptosis of RCC cells and expression levels of PI3K/Akt/NF-kB signaling pathway-related biomarkers were investigated using TUNEL staining and Western blotting methods, respectively. Effects of PAC on the inhibitory activity of RCC tumor in mice were evaluated in a 786-O CDX model. ResultsThe study found that PAC inhibited the viability of RCC cells in a dose-dependent manner, as demonstrated by in vitro cell assays (p < 0.05). However, PAC showed no significant inhibitory effect on normal renal cells (p > 0.05). PAC also significantly inhibited the migration and invasion of RCC via EMT/MMP signaling pathways (p < 0.05). Immunofluorescence and immunoblotting results showed that PAC induced the apoptosis of RCC, which was accompanied by changes in the expression levels of apoptosis-related proteins (p < 0.05). Moreover, PAC significantly downregulated the PI3K/Akt/NF-kB signaling pathway in a concentration-dependent manner (p < 0.05). The effect of PAC on RCC apoptosis was dramatically reversed by 740Y–P (PI3K agonist) (p < 0.05) but significantly enhanced in the presence of LY294002 (PI3K inhibitor) (p < 0.05). The results of in vivo experiment also demonstrated that the antitumor activity of PAC was achieved by affecting the PI3K/Akt/NF-kB signaling pathway. ConclusionsPAC can effectively suppress the proliferation, invasion and migration of RCC cells, and exhibit anti-tumor effects in RCC model by inhibiting the PI3K/Akt/NF-kB signaling pathway.

MMPs-related risk model identification and SAA1 promotes clear cell renal cell carcinoma migration via ERK-AP1-MMPs axis

Matrix Metalloproteinases (MMPs) have been demonstrated to be essential in facilitating the migration and metastasis of clear cell renal cell carcinoma (ccRCC). However, the ability of the MMP family to predict clinical outcomes and guide optimal therapeutic strategies for ccRCC patients remains incompletely understood. In this investigation, we initially conducted a thorough examination of the MMP family in pan-cancer. Notably, MMPs exhibited distinctive significance in ccRCC. Following this, we undertook an extensive analysis to evaluate the clinical value of MMPs and potential mechanisms by which MMPs contribute to the progression of ccRCC. A novel stratification method and prognostic model were developed based on MMPs in order to enhance the accuracy of prognosis prediction for ccRCC patients and facilitate personalized treatment. By conducting multi-omics analysis and transcriptional regulation analysis, it was hypothesized that SAA1 plays a crucial role in promoting ccRCC migration through MMPs. Subsequently, in vitro experiments confirmed that SAA1 regulates ccRCC cell migration via the ERK-AP1-MMPs axis. In conclusion, our study has explored the potential value of the MMP family as prognostic markers for ccRCC and as guides for medication regimens. Additionally, we have identified SAA1 as a crucial factor in the migration of ccRCC.

Acetyltransferase Tip60 inhibits the invasion and migration of renal cell carcinoma through JNK signaling

Acetyltransferase Tip60 inhibits the invasion and migration of renal cell carcinoma through JNK signaling

HIF1A-repressed PUS10 regulates NUDC/Cofilin1 dependent renal cell carcinoma migration by promoting the maturation of miR-194-5p.

Renal cell carcinoma (RCC) is characterized by a high rate of distant metastasis, which leads to poor prognosis in patients with advanced RCC. PUS10 has been recognized as a member of the pseudouridine synthase family, and recently other functions beyond the synthesis of the RNA modification have been uncovered. However, little is known about its role in diseases such as cancer. RT-qPCR, western blot and immunohistochemistry were used to measure the expression of PUS10 in RCC tissues. Transwell assay, wound healing assay, and in vivo metastasis model were conducted to determine the function of PUS10 in RCC progression. MicroRNA sequencing and GEO database were used to screen for the downstream microRNAs of PUS10. RNA immunoprecipitation, dual luciferase reporter assay, immunostaining, and rescue experiments were employed to establish the PUS10/miR-194-5p/nuclear distribution protein C(NUDC)/Cofilin1 axis in RCC migration. Chromatin immunoprecipitation and dual luciferase reporter assay were used to verify its upstream transcriptional regulator. The expression of PUS10 was significantly decreased in RCC tissues, and low expression predicted poor prognosis. In vitro and in vivo experiments showed that PUS10 suppressed RCC migration, which, however, was independent of its classical pseudouridine catalytic function. Mechanically, PUS10 promoted the maturation of miR-194-5p, which sequentially inhibited RCC migration via disrupting NUDC-dependent cytoskeleton. Furthermore, hypoxia and HIF-1A were found involved in the downregulation of PUS10. We unraveled PUS10 restrained RCC migration via the PUS10/miR-194-5p/NUDC/Cofilin1 pathway, which independent of its classical catalytic function. Furthermore, a linkage between the critical tumor microenvironment hallmark with malfunction of the forementioned metastasis inhibition mechanism was presented, as demonstrated by repressed expression of PUS10 due to hypoxia and HIF-1A.

Comprehensive analysis of single-cell RNA-seq and bulk RNA-seq revealed the heterogeneity and convergence of the immune microenvironment in renal cell carcinoma.

Substantial progress has been made in cancer biology and treatment in recent years, but the clinical outcome of patients with renal cell carcinoma (RCC) remains unsatisfactory. The tumor microenvironment (TME) is a potential target. By analyzing single-cell RNA sequencing (sc-RNAseq) data from six RCC tumor samples, this study identified 11 different cell types in the RCC cellular microenvironment, indicating a high degree of intratumoral heterogeneity. Through re-dimensionality reduction clustering of epithelial cells, neutrophils, macrophages, and T cells, we deeply reveal differences in the RCC tumor microenvironment. By analyzing differentially expressed genes in normal epithelial cells and malignant epithelial cells, we identify RNASET2 and GATM as potential prognostic biomarkers in RCC. In addition, by transcriptional factor analysis, we found significant differences in the expression of GZMK-CD8 T cell and B cell transcription factors between cancer tissues and normal tissues. By cell correlation analysis, we found significant correlations between neutrophils and macrophages and between IL7R-CD4 T cells and T regulatory (Treg) cells in RCC, which may be involved in the formation of immune TMEs. By cell developmental trajectory analysis, we showed that macrophages may be derived from neutrophils, whereas Treg cells may be derived from IL7R-CD4 T cells. By cell communication analysis, we found a clear interaction between macrophages and endothelial cells, neutrophils, and GZMK-CD8 T cells. In addition, we found that ADGRE5 signaling was mainly derived from mast cells and GZMK-CD8 T cells, and had a significant communication effect with neutrophils. The COLLAGEN signaling pathway is mainly derived from fibroblasts and has a significant communication effect with mast cells. Finally, we verified that RNASET2, which is highly expressed in epithelial cells, promotes proliferation and migration of RCC in vitro. RNASET2 is likely to be a potential target for renal cell carcinoma therapy. The results based on sc-RNAseq data analysis help to further elucidate the cellular microenvironment of RCC and provide help for cancer heterogeneity studies. This will help to provide more accurate personalized treatment for patients in clinical diagnosis.

KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF-1/CXCR4 axis.

Altered Krüppel-like factor 9 (KLF9) expression can regulate the progression of several cancers, including renal cell carcinoma (RCC). This study was conducted to investigate the role of KLF9 in the proliferation, invasion, and migration of RCC cells via regulation of stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4). The expression patterns of KLF9, SDF-1, and CXCR4 in the experimental cell lines were determined by real-time quantitative polymerase chain reaction and Western blotting. After transfection of the KLF9 siRNA and KLF9 pcDNA, cell proliferation, invasion, and migration were evaluated by experiments including cell counting kit-8, colony formation, and Transwell assays. The binding of KLF9 to the SDF-1 promoter was analyzed by chromatin immunoprecipitation and dual-luciferase assay. The rescue experiment was performed using the recombinant SDF-1 protein and KLF9 pcDNA. KLF9 was downregulated in the RCC cells. KLF9 knockdown induced the proliferation, invasion, and migration of RCC cells, whereas KLF9 overexpression elicited the opposite roles. Mechanically, KLF9 bound to the SDF-1 promoter, repressed SDF-1 transcription, and reduced the SDF-1/CXCR4 expression levels. Activation of the SDF-1/CXCR4 axis attenuated the inhibitory role of KLF9 overexpression in RCC cell growth. Ordinarily, KLF9 suppressed the proliferation, invasion, and migration of RCC cells by repressing the SDF-1/CXCR4 signaling.

Total Flavone Content of Cydonia oblonga Miller Inhibits Proliferation and Migration of Renal Carcinoma Cells by Inhibiting the S1PR2/FAK Pathway

Cydonia oblonga Miller (C. oblonga) is known for its beneficial properties for health since ancient times. C. oblonga has also been shown to possess antihemolytic, antidiabetic, and antilipoperoxidation, as well as lipid-lowering properties. Modern research has shown that C. oblonga also possess antitumor effects. However, studies have not reported whether its main compounds inhibit renal cell carcinoma (RCC) development and progression. We found the inhibitory effect of total flavone of C. oblonga (TFCOM) in RCC cells through in vitro screening tests. The molecular mechanism of this effect is still unknown. Therefore, molecular docking combined with network pharmacological methods was used in order to clarify the molecular mechanisms of TFCOM anticancer effects. TFCOM showed potent inhibitory effects on the proliferation and migration of 786-O and Renca cells. Hoechst 33342 staining test results indicated that TFCOM’s cell growth inhibition in RCC cells may be mediated through apoptosis. It may significantly influence S1PR2/FAK, WNT/β-catenin, and PI3K/AKT/mTOR signaling pathways that can regulate a series of cellular activities and can participate in the processes of cell proliferation, migration, and apoptosis. We conclude that TFCOM has antitumor activity against kidney cancer. It may induce apoptosis and inhibitory effects on cell proliferation and migration through S1PR2/FAK, WNT/β-catenin, and PI3K/AKT/mTOR signal pathways. TFCOM might be a potential anticancer drug to be further developed for human kidney cancer therapy. In recent years, many synthetic drugs with anticancer effects have the disadvantages of high price and side effects. Thus, the development of anticancer drugs from natural resources has its application value. Our results suggest that TFCOM, as a natural product, has multiple target effects, and it may act through proteins and receptors such as FAK and S1PR2, thereby affecting the activation of downstream proteins and inhibiting the occurrence and development of renal cancer cells.

Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database.

728 Background: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnoses at earlier clinical tumor stage and has rendered the phenomenon of the ‘small renal mass’ as a dominant presenting clinical paradigm. While thought of as being low risk, emerging knowledge about heterogeneity of RCC histologies and consequent impact on prognosis, in addition to awareness of impact of functional decline and demographic drivers on outcomes led us to further explore outcomes and predictive factors in T1a RCC patients treated with surgical resection. Methods: The INMARC database was queried for patients with small renal masses (≤ 4 cm) who underwent surgery via partial or radical nephrectomy and who presented without nodal or distant metastases. Patients were stratified into two groups based on having recurrence (distant or loco-regional) or not. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed to analyze clinicopathological variables associated with recurrence and identify predictors of recurrence, cancer-specific mortality (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) were performed to compare recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) between histology types clear cell, chromophobe, papillary, and “other.” Results: We analyzed 1,878 cT1aN0M0 RCC patients; 101 (5.4%) developed recurrence (median follow up 53.6 months; median time to recurrence 19.3 months); 51.1% developed distant recurrence, 35.6% had loco-regional recurrence, and 13.9% experienced distant and loco-regional recurrence. MVA demonstrated age (HR=1.02, p=0.02), sex (HR=1.71, p=0.045), diabetes (HR=1.94, p=0.006), high/unclassified grade (HR=2.82-4.40, p&lt;0.001-0.007), papillary (HR=0.37, p=0.013) and other (HR=2.51, p=0.019) RCC as predictive factors for recurrence. MVA identified high/unclassified grade (HR=3.17-6.22, p=0.002-0.003) and papillary RCC (HR=0.12, p=0.036) as predictive factors for CSM. MVA for ACM demonstrated age (HR=1.03, p&lt;0.001), non-Caucasian race (HR=0.85, p&lt;0.001), high grade (HR=1.42, p=0.024), recurrence (HR=1.86, p=0.003), and GFR&lt;45 (HR=2.89, p&lt;0.001) to be independent risk factors. KMA comparing Clear Cell, Papillary, Chromophobe and Other RCC revealed significant differences for 5-year CSS (97.8% vs. 99.3% vs. 98.5% vs. 87.0%, p=0.018) and 5-year RFS (92.4% vs. 96.0% vs. 97.8% vs. 81.7%, p&lt;0.001), but not 5-year OS (89.4% vs. 85.2% vs. 93.2% vs. 73.7%, p=0.34). Conclusions: We noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. These findings suggest consideration to refine management and post treatment surveillance strategies in T1a RCC.

MiR-613 suppresses renal cell carcinoma proliferation, invasion and migration by regulating the AXL/AKT pathway.

In the last few decades, microRNAs (miRNAs) are possible to effectively control and treat cancer. However, the function of miR-613 in renal cell carcinoma (RCC) is not very clear up to now. Here, the direction of this research was to investigate the influence of miR-613 for the proliferation, invasion and migration of RCC, and the underlying molecular mechanism. First, the mRNA and protein expression levels of miR-613 were determined in RCC tissues and cancer cells (786-O and ACHN). Using bioinformatics and literature review, anexelekto (AXL), as the target of miR-613 in renal cell carcinoma, was screened. Phenotype experiment and mechanism experiment illustrated the targeting relationship between miR-613 and AXL in cancer cells. Furthermore, a rescue assay with AXL overexpression was performed to make a profound study whether miR-613 disturbs RCC proliferation, invasion, and migration through direct regulation of AXL. Finally, through experiment in vivo, we observe the influence of miR-613 overexpression for tumor. These results were as follows. The present findings proved, in RCC, that the production of miR-613 was at a low level. Except for this point, this current research confirmed, in RCC cells, that the upregulation of miR-613 can control proliferation, metastasis, and invasion by reducing AXL levels and controlling the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway.

Retracted: Inhibitory Effect of Ursolic Acid on Proliferation and Migration of Renal Carcinoma Cells and Its Mechanism.

[This retracts the article DOI: 10.1155/2022/1529132.].

Study on the Role and Mechanism of LncRNA ZFasL in Renal Carcinoma.

Background Renal carcinoma is the 7th most common cancer in the world, with the 7th and 6th highest incidence and mortality rates worldwide. Although great progress has been made in the diagnosis and treatment of renal carcinoma, its prognosis is still unsatisfactory. It is important to study the molecular mechanisms of renal carcinoma occurrence and development and to find potential therapeutic targets. Objective The main objective is to investigate the effects of long noncoding RNA (lncRNA) ZFAS1 (lncZFAS1) on the proliferation, apoptosis, and migration of renal carcinoma cells and to preliminarily explore its mechanism. Methods A qRT-PCR method was used to detect the expression of lncZFAS1 in renal carcinoma tissues and renal carcinoma cells. After shRNA interference with lncZFAS1 expression, the effects of lncZFAS1 on cell proliferation, apoptosis, migration, and invasion were detected by CCK-8 method, flow cytometry, scratch test, and Transwell assay. The effect of the knockdown of lncZFAS1 on the growth of transplanted tumors was examined. The expression of lncZFAS1 in renal carcinoma tissues and renal carcinoma cells was significantly higher than that in paracancerous tissues and normal esophageal epithelial cells. Knockdown of lncZFAS1 significantly inhibited the proliferation, migration, and invasive ability of renal carcinoma cells; upregulated miR-150-5P expression and downregulated HMGA2 expression in renal carcinoma cells; and significantly inhibited the growth of transplanted tumors in nude mice. Conclusion Upregulation of miR-150-5P expression was detected after knockdown of lncZFAS1 in renal carcinoma cells, while both mRNA and protein expression levels of HMGA2 were decreased. lncZFAS1 can promote the proliferation and migration of renal carcinoma cells, and the mechanism may be related to the regulation of the miR-150-5P/HMGA2 molecular axis.

Inhibitory Effect of Ursolic Acid on Proliferation and Migration of Renal Carcinoma Cells and Its Mechanism.

Background Renal carcinoma is one of the most common malignant tumors in the urinary system. Autophagy can be both activated and inhibited in renal carcinoma, and it plays a double-edged role in the development of renal carcinoma. In the early stage of cancer, autophagy can suppress tumors. In the late stage, autophagy contributes to the survival of tumor cells in an unfavorable environment, and some autophagy-related proteins P62, LC3B, and beclin-1 have become indicators of the prognosis of patients with renal carcinoma. Aim To demonstrate that ursolic acid activates autophagy in renal carcinoma 786-O cells by inhibiting the hedgehog signaling pathway. Methods The effect of ursolic acid on the viability of 786-O cells was determined by the MTT method; the effect of ursolic acid on the proliferation and migration of 786-O cells was examined by crystalline violet staining and scratch assay, respectively. For the study of autophagy, we firstly screened the time points. Western blot assay was used to detect the expression level of autophagic protein P62 at different time points of ursolic acid on 786-O. Then, the Cell MeterTM Autophagy Assay Kit was used to detect the effect of different doses of ursolic acid on the autophagic fluorescence intensity of 786-O cells; the Western blot method was used to detect the effect of different doses of ursolic acid on the expression levels of LC3II and P62 proteins in 786-O cells. Further, AdPlus-mCherry-GFP-LC3B adenovirus transfection was used to detect the effect of ursolic acid on the autophagic flow of 786-O cells; ursolic acid was combined with the autophagy inhibitor chloroquine (CQ) to detect the expression level of autophagy protein LC3II by Western blot. In terms of mechanism, the effect of ursolic acid on hedgehog signaling pathway-related proteins in 786-O cells was detected by Western blot. Results Ursolic acid inhibited the activity, proliferation, and migration of 786-O cells, enhanced the fluorescence intensity of autophagosomes in 786-O cells, increased the expression level of autophagy marker protein LC3II, and inhibited the expression level of P62 in a time and dose-dependent manner; ursolic acid activated the autophagic flow in 786-O cells, which showed that ursolic acid caused the accumulation of autophagic fluorescent spots and enhanced the fluorescence intensity of autophagosomes. Ursolic acid activated the autophagic flow in 786-O cells, as evidenced by the accumulation of autophagic fluorescent spots and enhanced fluorescence intensity of autophagosomes, and the combined use of the autophagy inhibitor CQ increased the expression level of LC3II compared to ursolic acid alone; ursolic acid decreased the expression levels of PTCH1, GLI1, SMO, SHH, and c-Myc and increased the expression level of Sufu in the hedgehog signaling pathway. Conclusion Ursolic acid activates autophagy in renal carcinoma 786-O cells, probably by inhibiting hedgehog signaling pathway activity.

PD43-10 CANCER-ASSOCIATED ADIPOSE-DERIVED MESENCHYMAL STEM CELLS PROMOTE MIGRATION AND INVASION IN KIDNEY CANCER

You have accessJournal of UrologyCME1 May 2022PD43-10 CANCER-ASSOCIATED ADIPOSE-DERIVED MESENCHYMAL STEM CELLS PROMOTE MIGRATION AND INVASION IN KIDNEY CANCER Yumina Muto, Kazuyuki Numakura, Yuya Sekine, Mizuki Kobayashi, Soki Kashima, Ryohei Yamamoto, Atsushi Koizumi, Taketoshi Nara, Mitsuru Saito, Shintaro Narita, Yasufumi Omori, and Tomonori Habuchi Yumina MutoYumina Muto More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Yuya SekineYuya Sekine More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Soki KashimaSoki Kashima More articles by this author , Ryohei YamamotoRyohei Yamamoto More articles by this author , Atsushi KoizumiAtsushi Koizumi More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Yasufumi OmoriYasufumi Omori More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002604.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Adipose-derived mesenchymal stem cells (A-MSCs) are known to be a preeminent contributor to tumor microenvironments. Their role in renal cell carcinoma (RCC) has not been entirely investigated. This study aimed to clarify the significance of A-MSCs in RCC. METHODS: Human A-MSCs were isolated from the perirenal fat in RCC patients (RCC-MSC) and kidney transplantation donors (Donor-MSC) for use as controls. Several RCC cell lines were co-cultured with the A-MSCs, then analyzed for their migration and invasive ability. Molecular pathways activated in the RCC-MSCs and isolated RCC cultures were assessed. Beta-catenin in perirenal fat from surgical specimens from RCC patients was stained by immunohistochemistry (IHC). RESULTS: RCC-MSCs expressed higher levels of mRNAs encoding Hes1, Hey1, and Twist, higher protein levels of beta-catenin, and reduced protein levels of phospho-Akt (Ser473) and phospho-p38 MAPK relative to Donor-MSCs (Figure 1A and B). These results suggest that RCC-MSC stemness is reduced compared with Donor-MSCs in terms of stemness associated molecular pathways. This finding was confirmed by the aldehyde dehydrogenase enzymatic activity (ALDH) assays, in which fewer RCC-MSCs were ALDH+ than Donor-MSCs (Figure 1C). We next analyzed cell function by co-culturing with RCC cell lines. Tumor cell migration was significantly elevated in RCC-MSC cultures compared with RCC cell lines cultured alone (Figure 2A and B). Pathway screening using the RCC cell line revealed elevated urokinase-type plasminogen activator (uPA) mRNA expression in RCC-MSCs than cultured alone (Figure 2C). In RCC surgical specimens, IHC of perirenal stromal tissue for beta-catenin showed a high positive correlation with tumor aggressiveness (Figure 2D). CONCLUSIONS: Co-culturing of RCC-MSCs with RCC cell lines exacerbated tumor invasiveness. Interaction between A-MSCs and tumors may promote A-MSC differentiation from pluripotent stem cells, and facilitate RCC migration and invasion by increasing expression of uPA in tumor cells. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e706 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yumina Muto More articles by this author Kazuyuki Numakura More articles by this author Yuya Sekine More articles by this author Mizuki Kobayashi More articles by this author Soki Kashima More articles by this author Ryohei Yamamoto More articles by this author Atsushi Koizumi More articles by this author Taketoshi Nara More articles by this author Mitsuru Saito More articles by this author Shintaro Narita More articles by this author Yasufumi Omori More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF DownloadLoading ...

LncRNA GIHCG promoted the proliferation and migration of renal cell carcinoma through regulating miR-499a-5p/XIAP axis

BackgroundOur previous study demonstrated that lncRNA GIHCG is upregulated in renal cell carcinoma (RCC) and that knockdown of lncRNA GIHCG suppresses the proliferation and migration of RCC cells. However, the mechanism of lncRNA GIHCG in RCC needs further exploration. MethodsThe proliferation, cell cycle, migration, and apoptosis of RCC cells were tested using CCK-8, flow cytometry, wound healing and Annexin-V/-FITC/PI flow cytometry assays, respectively. Dual-luciferase reporter and RNA pull-down or RNA immunoprecipitation assays (RIPs) were performed to analyze the interactions among lncRNA GIHCG, miR-499a-5p and XIAP. A tumour xenograft study was conducted to verify the function of lncRNA GIHCG in RCC development in vivo. ResultsKnockdown of lncRNA GIHCG inhibited cell proliferation and migration and induced G0/G1 arrest while promoting apoptosis. Overexpression of lncRNA GIHCG led to the opposite results. LncRNA GIHCG sponged miR-499a-5p and downregulated its expression in RCC cells. MiR-499a-5p overexpression suppressed RCC cell growth. MiR-499a-5p targeted XIAP and inhibited its expression. LncRNA GIHCG knockdown reduced the growth of tumour xenografts in vivo and the expression of XIAP while increasing miR-499a-5p levels. ConclusionLncRNA GIHCG accelerated the development of RCC by targeting miR-499a-5p and increasing XIAP levels.

A novel role of TCAIM: suppressing renal carcinoma growth and enhancing its sensitivity to sunitinib.

Renal carcinoma is a common malignancy for which the underlying molecular mechanisms warrant further investigation. T cell activation inhibitor mitochondrial (TCAIM), a mitochondrial protein, was found to be expressed to a low extent in renal carcinoma specimens. However, its role in carcinomas remains unclear. In the present study, the role of TCAIM in renal carcinoma was explored through loss-of-function and gain-of-function experiments. Here, we showed that TCAIM delayed the growth of renal carcinoma cells both in vitro and in vivo by modulating their cell cycle progress. Additionally, TCAIM also enhanced their sensitivity to sunitinib by aggravating apoptosis. Furthermore, TCAIM also decreased the adhesion and migration of renal carcinoma cells. Moreover, the transcription of TCAIM was regulated by vitamin D receptor, which acts as a transcriptional factor. To identify the pathways regulated by TCAIM, 425 unique proteins bound to TCAIM were pulled down through co-immunoprecipitation and analyzed by mass spectrometry followed by Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis. In summary, the present study reveals a tumor-suppressor role of TCAIM in renal carcinoma cells, as well as its upstream regulation and downstream potential mechanisms. Our study provides theoretical bases and novel insights with respect to the development of new therapeutic strategies for the treatment of renal carcinoma.

Isothiocyanate From Moringa oleifera Seeds Inhibits the Growth and Migration of Renal Cancer Cells by Regulating the PTP1B-dependent Src/Ras/Raf/ERK Signaling Pathway.

Moringa oleifera Lam. is a tropical and subtropical plant that has been used for centuries as both food and traditional medicine. 4-[(α-L-Rhamnosyloxy) benzyl] isothiocyanate (MIC-1) is an active substance in M. oleifera, with anti-cancer activity. However, whether MIC-1 exerts anti-renal cancer effects is unknown. Therefore, the aim of the present study was to evaluate the effects of MIC-1 on the growth and migration of renal cell carcinoma (RCC) cells and to identify the putative underlying mechanism. We found that, among 30 types of cancer cells, MIC-1 exerted the strongest growth inhibitory effects against 786-O RCC cells. In addition, MIC-1 (10 μM) significantly inhibited the growth of five RCC cell lines, including 786-O, OSRC-2, 769-P, SK-NEP-1, and ACHN cells, but was not toxic to normal renal (HK2) cells. Also, MIC-1 suppressed 786-O and 769-P cell migration and invasion abilities, and reduced the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, MIC-1 induced apoptosis and cell cycle arrest, increased Bax/Bcl-2 ratio, and decreased cell cycle-related protein expression in 786-O cells and 769-P cells. Molecular docking and small-molecule interaction analyses with PTP1B both showed that MIC-1 inhibited PTP1B activity by binding to its active site through hydrogen bonding and hydrophobic interactions. Additionally, MIC-1 could suppress the growth and migration of 786-O cells by inhibiting PTP1B-mediated activation of the Src/Ras/Raf/ERK signaling pathway. In vivo experiments further showed that MIC-1 markedly inhibited the growth of xenograft tumors in mice, and greatly increased Bax/Bcl-2 ratio in tumor tissues. In addition, MIC-1 had no effect on the PTP1B-dependent Src/Ras/Raf/ERK signaling pathway in HCT-116 cells, Hep-G2 cells, and A431 cells. Overall, our data showed that MIC-1 could be a promising, non-toxic, natural dietary supplement for the prevention and treatment of renal cancer.

Retraction.

Retraction: "MicroRNA-363 inhibits angiogenesis, proliferation, invasion, and migration of renal cell carcinoma via inactivation of the Janus tyrosine kinases 2-signal transducers and activators of transcription 3 axis by suppressing growth hormone receptor gene," Jie Zhu, Da-Qing Zhu, Yu Zhang, Qi-Ming Liu, Peng-Chao Wang, Hong-Zhao Li, Xin Ma, and Xu Zhang, J Cell Physiol. 2019; 2581-2592: The above article, published online on 19 September 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/jcp.27020) has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed after the authors asked to retract their paper. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid.

EDITORIAL COMMENT

The increased use of cross-sectional imaging has led to significant stage migration in renal cell carcinoma (RCC). As more computed tomography (CT) and magnetic resonance imaging scans are performed for unrelated conditions, more RCCs have been detected – particularly small, asymptomatic lesions. For larger RCCs, obtaining chest imaging to rule out synchronous lung metastasis (sLM) remains an important clinical principle, supported by current guidelines. However, regarding chest imaging, guidelines do not necessarily reflect the stage migration in RCC over the past decade. 1 Campbell S Uzzo RG Allaf ME et al. Renal mass and localized renal cancer: AUA Guideline. J Urol. 2017; 198 ([cited 10/1/2020]): 520-529 Crossref PubMed Scopus (648) Google Scholar As smaller, more indolent, RCCs are detected the optimal role of chest imaging with initial RCC diagnosis remains unclear.

M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT

ObjectiveM2 macrophages are associated with a poor prognosis in a variety of malignancies. There are, however, few relevant investigations in clear cell renal cell carcinoma (ccRCC).MethodsThe expression of M2 macrophages in ccRCC tissues was first discovered using immunohistochemistry in this study. Then, M2 macrophages were created in vitro to see how they affected the proliferation, migration, invasion, and EMT of ccRCC cells. Using qPCR and prognostic analysis identifies important chemokine. Antibody neutralization tests confirmed the chemokine’s involvement and function. Pathway inhibitors confirmed the main pathway of M2 macrophages in ccRCC. Finally, qPCR and IHC were used to confirm the expression of chemokine receptors in ccRCC tissues.ResultsThe presence of M2 macrophages was linked to a poor outcome in ccRCC. M2 macrophages enhanced the proliferation, migration, invasion, and EMT of ccRCC lines in vitro. CXCL13 was identified as the main chemokine by prognostic analysis and qPCR tests. CXCL13 neutralizing antibodies can inhibit the stimulation of M2 macrophages in ccRCC lines’ proliferation, migration, invasion, and EMT. M2 macrophages and CXCL13 may activate the Akt pathway in ccRCC lines, and Akt inhibitors decrease ccRCC lines proliferation, migration, invasion, and EMT. CXCR5 expression is a poor prognostic factor for renal cell carcinoma, according to qPCR and immunohistochemistry. In vivo experiments further proved that CXCL13 secreted by M2 macrophages can promote tumor proliferation.ConclusionsM2 macrophages in the immunological milieu secrete CXCL13, which promotes ccRCC proliferation, migration, invasion, and EMT. Our findings contribute to a better understanding of the function of the tumor microenvironment in the incidence and progression of ccRCC, and they may point to novel therapeutic targets for ccRCC.