Search

The article titled "[Retracted] miR-660-5p is associated with cell migration, invasion, proliferation and apoptosis in renal cell carcinoma" was published in Molecular Medicine Reports in 2018. The authors of the article contacted the Editorial Office to report errors in the data handling and labeling of representative images in Figures 3B and 5A. An independent investigation by the Editorial Office revealed overlapping data panels in Figures 6A and 6B, indicating a lack of confidence in the presented data. As a result, the Editor decided to retract the paper. The authors accepted this decision, and the Editor apologizes for any inconvenience caused. [Extracted from the article]

Growing evidence indicates that circular RNAs (circRNAs) are promising biomarkers, as they play significant roles in the development of various cancers. The circular RNA MYLK (circMYLK) has been reported to be involved in the development of malignant tumours, including liver, prostate and bladder cancers. Nevertheless, the biological function of circMYLK in renal cell carcinoma (RCC) remains unclear. In this study, we observed that circMYLK is notably up‐regulated in RCC. Increased circMYLK expression led to a larger tumour size, distant metastasis and poor prognosis of RCC patients. Moreover, circMYLK silencing repressed RCC growth and metastasis in vitro and in vivo. Mechanistically, circMYLK can capture miR‐513a‐5p to facilitate VEGFC expression and further promote the tumorigenesis of RCC cells. In summary, our findings demonstrate that circMYLK has an oncogenic role in RCC growth and metastasis by modulating miR‐513a‐5p/VEGFC signalling. Thus, circMYLK has potential as a diagnostic biomarker and therapeutic target in the treatment of RCC. [ABSTRACT FROM AUTHOR]

The abundant and reversible N6‐methyladenosine (m6A) RNA modification and its modulators have important roles in regulating various gene expression and biological processes. Here, we demonstrate that fat mass and obesity associated (FTO), as an m6A demethylase, plays a critical anti‐tumorigenic role in clear cell renal cell carcinoma (ccRCC). FTO is suppressed in ccRCC tissue. The low expression of FTO in human ccRCC correlates with increased tumour severity and poor patient survival. The Von Hippel‐Lindau‐deficient cells expressing FTO restores mitochondrial activity, induces oxidative stress and ROS production and shows impaired tumour growth, through increasing expression of PGC‐1α by reducing m6A levels in its mRNA transcripts. Our work demonstrates the functional importance of the m6A methylation and its modulator, and uncovers a critical FTO‐PGC‐1α axis for developing effective therapeutic strategies in the treatment of ccRCC. [ABSTRACT FROM AUTHOR]

Background/Aims: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. Methods: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue. The inhibition of ACSS2 expression was achieved by RNA interference, which was confirmed by qRT-PCR and Western blotting. Cell proliferation and apoptosis were detected by a CCK8 assay and a flow cytometry analysis, respectively. Cell migration and invasion were determined by the scratch and transwell assays. Following the knockdown of ACSS2 expression, the expression of the autophagy-related factor LAMP1 was measured by qRT-PCR and Western blotting. Results: Compared to adjacent tissues, ACSS2 expression was upregulated in RCC cancer tissues and positively correlated with metastasis. Inhibition of ACSS2 had no effect on RCC cell proliferation or apoptosis. However, decreased ACSS2 expression was found to inhibit RCC cell migration and invasion. ACSS2 was determined to promote the expression of LAMP1, which can also promote cell migration. This pathway may be considered a potential mechanism through which ACSS2 participates in RCC development. Conclusion: These data suggest that ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1. Taken together, these findings reveal a potential target for the diagnosis and treatment of RCC. [ABSTRACT FROM AUTHOR]

Multilocular cystic renal cell carcinoma (MCRCC), which exhibits low-stage and low-grade characteristics, is a special type of RCC. MCRCC is extremely rare and generally develops at ages >50 years. We herein report a case of MCRCC in a 28-year-old man, which, to the best of our knowledge, is the youngest case reported worldwide to date. The patient presented with irritative bladder symptoms for 1 year. Dynamic enhanced computed tomography (CT) imaging revealed a mass with inhomogeneous enhancement in the left kidney, with a rich blood supply. B-ultrasonography also revealed a renal protruding mass. As the mass was highly suspicious to be a malignant tumor, laparoscopic radical nephrectomy was performed and MCRCC was definitively diagnosed by pathological examination. The patient has been regularly followed up for 6 months, without complications or disease recurrence. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system with poor prognosis. microRNAs (miRNAs) are a class of small, non-coding RNA molecules that serve important roles in biological and pathological processes in several types of human tumors. miRNA (miR)-660-5p is dysregulated in many human cancers; however, its role in renal cell carcinoma is currently unclear. In the present study, reverse transcription-quantitative polymerase chain reaction was performed to examine the expression levels of miR-660-5p in RCC tissues and paired normal adjacent tissues (NATs). To determine the function of miR-660-5p in RCC cells, wound-healing and Matrigel assays were performed to determine the effects of miR-660-5p on cell migration and invasion, respectively. MTT and Cell Counting kit-8 assays were performed to determine the effects of miR-660-5p on RCC cell proliferation. In addition, flow cytometric analysis was performed to validate the effects of miR-660-5p on apoptosis. The results indicated that miR-660-5p expression was downregulated in RCC tissues compared with NATs. Restoration of miR-660-5p expression using synthetic mimics may suppress cell migration, invasion and proliferation, and induce cell apoptosis, while using synthetic inhibitors may promote cell migration, invasion and proliferation, and suppress cell apoptosis. These results suggested that miR-660-5p may serve a tumor suppressive role in RCC tumorigenesis. [ABSTRACT FROM AUTHOR]

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-020-01225-2. [ABSTRACT FROM AUTHOR]

Purpose: The aims of this study were to evaluate the clinical significance and potential prognostic value of pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) in clear cell renal cell carcinoma (ccRCC) patients. Materials and Methods: The expression of PNCK mRNA was determined in 24 paired samples of ccRCCs and adjacent normal tissues using real-time RT-PCR. The expression of PNCK was determined in 248 samples of ccRCCs and 92 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between PNCK expression and the clinical features of ccRCC. Results: The mRNA level of PNCK was significantly higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). An immunohistochemical analysis of 92 paired tissue specimens showed that PNCK expression was higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). Moreover, there was a significant correlation between the PNCK expression and various clinicopathological parameters such as Fuhrman grade (p = 0.011), tumor size (p<0.001), T stage (p<0.001) and N stage (p = 0.015). Patients with higher PNCK expression had shorter overall survival time than those with lower PNCK expression (p<0.001). Multivariate analysis indicated that PNCK expression was an independent predictor for poor survival of ccRCC patients. Conclusions: To our knowledge, this is the first study that determines the relationship between PNCK and prognosis in ccRCC. We found that increased PNCK expression is associated with poor prognosis in ccRCC. PNCK may represent a novel prognostic marker for ccRCC. [ABSTRACT FROM AUTHOR]

We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ?1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the ubiquitin-mediated proteolysis pathway (UMPP), and alterations in the UMPP were significantly associated with overexpression of HIF1? and HIF2? in the tumors (P = 0.01 and 0.04, respectively). Our findings highlight the potential contribution of UMPP to ccRCC tumorigenesis through the activation of the hypoxia regulatory network. [ABSTRACT FROM AUTHOR]

Although renal cell carcinoma (RCC) is a common malignant urological cancer, its pathogenesis remains unclear. Previous studies have indicated that miR‐140‐5p acts as a tumor suppressor in various tumors, including bladder cancer, hepatocellular carcinoma, and gastric cancer, but its biological function in RCC remains unknown. In the present study, we found that miR‐140‐5p was upregulated in RCC tissues, whereas Krüppel‐like factor 9 (KLF9) was downregulated and correlated inversely with miR‐140‐5p in RCC tissues. miR‐140‐5p promoted the proliferation, migration, and invasion of RCC cells in vitro, and knockdown of miR‐140‐5p significantly suppressed tumor growth and lung metastasis in nude mouse model of RCC. We also found that miR‐140‐5p significantly suppressed the expression of KLF9 by binding to the 3ʹ‐UTR of KLF9 mRNA and that KLF9, as a transcription factor, upregulates KCNQ1 (also called Kv7.1 and KvLQT1) expression by binding to the site (−841/−827) in the KCNQ1 promoter region in RCC cells. Moreover, forced expression of KCNQ1 decreased the growth and metastasis of RCC cells. These results suggest that the miR‐140‐5p/KLF9/KCNQ1 axis functions as a key signaling pathway in RCC progression and metastasis and represents a potential target of RCC therapies. [ABSTRACT FROM AUTHOR]

Highlights • MiR-31-5p is downregulated in RCC tissues and cell lines. • miR-31-5p downregulation was associated with poor prognosis in RCC patients. • Overexpression of miR-31-5p inhibited RCC cell proliferation, migration and invasion and cell cycle. • CDK1 is the novel target gene of miR-31-5p. Abstract Background: Renal cell carcinoma (RCC) accounts for more than 90% of cancers in the kidney. RCC is often asymptomatic, as a result people with RCC generally have advanced disease by the time it is discovered and has a poor prognosis compared to other cancers. Therefore, it is necessary to explore its pathogenesis and identify some reliable prognostic biomarker of RCC. miRNAs are emerging as important players in the development and progression of RCC. miR-31-5p has been reported to act as a tumor suppressor in hepatocellular carcinoma (HCC). The aim of this study is to determine the detailed molecular mechanism of miR-31-5p in the progression of RCC and to investigate its potential clinical value. Methods: In this study, RT-qPCR, EdU assay, CCK-8 assay, wound scratch assay, transwell assay, flow cytometry assay and cell cycle assay were performed to detect miR-31-5p expression and its functions in RCC. Moreover, 42 formalin-fixed paraffin-embedded (FFPE) RCC samples were used to analyze the relationship between miR-31-5p expression and patients' overall survival. Finally, luciferase reporter assay, RT-qPCR assay and western blot were used to explore the association between miR-31-5p and its potential targets. Results: miR-31-5p was significantly down-regulated in RCC tissues and RCC cell lines compared with paired adjacent normal tissues and normal cell lines. miR-31-5p downregulation was associated with poor prognosis in RCC patients. Overexpression of miR-31-5p inhibited RCC cell proliferation, migration and invasion and cell cycle. Conversely, down-regulation of miR-31-5p promoted cell proliferation, migration and invasion. Furthermore, cyclin-dependent kinasec1 (CDK1), a key player in cell cycle regulation, was identified as a functional target of miR-31-5p. Conclusions: Our results suggest that miR-31-5p serves as a tumor suppressor in RCC and is expected to be a molecular biomarker for poor prognosis of RCC. [ABSTRACT FROM AUTHOR]

Abstract Background Renal cell carcinoma (RCC) is a most common kidney malignancy, with atypical symptoms in the early stage and poor outcome in the late stage. Recently, emerging evidence revealed that some miRNAs play an essential role in the tumorigenesis and progression of RCC. Therefore, the aim of this study is that understand the detailed molecular mechanism of miR-23a-3p in RCC and identify its potential clinical value. Methods In this study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay and flow cytometry assay were performed to detect miR-23a-3p expression and its proliferation, migration and apoptosis in RCC. The bioinformatics analysis, RT-qPCR, western blot and luciferase reporter assay were performed to discern and examine the relationship between miR-23a-3p and its potential targets. Moreover, we analyzed the relationship between miR-23a-3p expression and clinicopathological variables or overall survival (OS) from 118 formalin-fixed paraffin-embedded RCC samples. Results miR-23a-3p is significantly up-regulated in RCC tissue samples, RCC cell lines and the TCGA database. Upregulating miR-23a-3p enhances, while silencing miR-23a-3p suppresses cell viability, proliferation and mobility in ACHN and 786-O cell lines. Besides, overexpression of miR-23a-3p inhibits the cell apoptosis. Then our study further reveals that miR-23a-3p regulates tumorigenesis by targeting Proline-Rich Nuclear Receptor Coactivator 2 (PNRC2). Also, the cox proportional hazard regression analysis indicates that low expression of miR-23a-3p patients has a remarkable longer OS. Conclusions Our results reveals that miR-23a-3p may not only serve as a new biomarker for prognosis but also serve as a new therapeutic strategy in the RCC treatment. [ABSTRACT FROM AUTHOR]

Background MicroRNA(miRNA) plays a key regulatory role in various stages of tumorigenesis, including cell growth, cell cycle control, apoptosis avoidance, tissue invasion, and metastasis. Several microRNAs are involved in the development of renal cell carcinoma (RCC) and the malignant transformation process. However, the effects of miR-663a on RCC have rarely been reported. Methods In the present study, the expression of miR-663a was examined in RCC using matched normal kidney tissues and four cell lines (786-O, Caki-1, ACHN and HK-2). MicroRNA mimics were transiently transfected into RCC cells and the effects of over expression on proliferation, migration, invasion, and apoptosis was observed. In addition, the relationship between miR-663a expression in 42 formalin-fixed paraffin-embedded (FFPE) clear cell renal carcinoma (ccRCC) samples and clinical pathological variables and overall survival was investigated. We evaluated the prognostic value of miR-663a expression in ccRCC by experimental results. Results The results showed that the expression of miR-663a was up-regulated in RCC cells and tissues and miR-663a was associated with proliferation, migration, invasion, and apoptosis of RCC. Cox proportional hazard regression analysis showed that a high expression of miR-663a patients had a significantly shorter overall survival in univariate and multivariate analysis. Kaplan-Meier survival curves showed that a high expression of miR-663a patients had a significantly shorter overall survival. Conclusions These results indicate that miR-663a can be used as an independent marker for the poor prognosis of ccRCC, and may also play an important role as a tumor oncogene in the occurrence and development of RCC. [ABSTRACT FROM AUTHOR]

Background Renal cell carcinoma (RCC), a heterogeneous type of cancer originating from the nephron, occupies approximately 3.9% of new carcinomas, with an increasing incidence in the past two decades. The most common subtype of renal cell carcinoma is clear cell RCC (ccRCC). Though surgery and other treatments are applied to RCC, it has the highest recurrence rate and mortality rate among the genitourinary cancers. As the study progressed, miRNAs are found to be the biomarkers for tumor diagnosis, prognosis and the targets for tumor management. Methods In present study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay and flow cytometry assay were performed to ascertain miR-566 expression level and its proliferation, migration and apoptosis in RCC. Moreover, we analyzed the relation between miR-566 expression and clinicopathological variables or overall survival from the 42 formalin-fixed paraffin-embedded (FFPE) renal cancer samples. We further evaluate prognostic values of miR-566 expression. Results miR-566 is up-regulated in RCC tissue samples and renal carcinoma cell lines. miR-566 promotes cell proliferation, mobility and inhibits cell apoptosis in 786-O and ACHN cell lines. Cox proportional hazard regression analysis indicates that low expression of miR-566 patients have a remarkable longer overall survival in the univariate and multivariate analysis. The Kaplan–Meier survival curves show that the low expression of miR-566 patients have a remarkable longer overall survival. Conclusions The results of the current study demonstrate that oncogene miR-566 is a potential biomarker not only for diagnosis but also for prognosis for RCC. [ABSTRACT FROM AUTHOR]

Summary: Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies. [ABSTRACT FROM AUTHOR]