scholarly journals LncRNA CDKN2B-AS1 stabilized by IGF2BP3 drives the malignancy of renal clear cell carcinoma through epigenetically activating NUF2 transcription

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xina Xie ◽  
Jiatian Lin ◽  
Xiaoqin Fan ◽  
Yuantang Zhong ◽  
Yequn Chen ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Survival Data ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Binding Protein ◽  
Renal Clear Cell Carcinoma ◽  
Receiver Operating Curve ◽  
Migration And Invasion ◽  
Integrated Analysis

AbstractBecause of the lack of sensitivity to radiotherapy and chemotherapy, therapeutic options for renal clear cell carcinoma (KIRC) are scarce. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of cancer. However, their functional roles and upstream mechanisms in KIRC remain largely unknown. Exploring the functions of potential essential lncRNAs may lead to the discovery of novel targets for the diagnosis and treatment of KIRC. Here, according to the integrated analysis of RNA sequencing and survival data in TCGA-KIRC datasets, cyclin-dependent kinase inhibitor 2B antisense lncRNA (CDKN2B-AS1) was discovered to be the most upregulated among the 14 lncRNAs that were significantly overexpressed in KIRC and related to shorter survival. Functionally, CDKN2B-AS1 depletion suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, CDKN2B-AS1 exerted its oncogenic activity by recruiting the CREB-binding protein and SET and MYND domain-containing 3 epigenetic-modifying complex to the promoter region of Ndc80 kinetochore complex component (NUF2), where it epigenetically activated NUF2 transcription by augmenting local H3K27ac and H3K4me3 modifications. Moreover, we also showed that CDKN2B-AS1 interacted with and was stabilized by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal protein showing increased levels in KIRC. The Kaplan–Meier method and receiver operating curve analysis revealed that patients whose IGF2BP3, CDKN2B-AS1 and NUF2 are all elevated showed the shortest survival time, and the combined panel (containing IGF2BP3, CDKN2B-AS1, and NUF2) possessed the highest accuracy in discriminating high-risk from low-risk KIRC patients. Thus, we conclude that the stabilization of CDKN2B-AS1 by IGF2BP3 drives the malignancy of KIRC through epigenetically activating NUF2 transcription and that the IGF2BP3/CDKN2B-AS1/NUF2 axis may be an ideal prognostic and diagnostic biomarker and therapeutic target for KIRC.

scholarly journals The Clinical Relevance and Tumor Promoting Function of C19orf10 in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanxin Lu ◽  
Ximian Liao ◽  
Tongyu Wang ◽  
Xiaowei Hong ◽  
Zesong Li
Keyword(s):  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Akt Signaling ◽  
Receiver Operating Curve ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Cox Regression Analysis

Kidney renal clear cell carcinoma (KIRC) is the most common primary renal neoplasms. Currently, there are few molecular indicators and therapeutic targets that can be used in diagnostic and prognostic assessment. In this study, we identified the C19orf10 expression in KIRC specimens and explored the diagnostic and prognostic value of C19orf10 in KIRC using TCGA and CPTAC database. Loss-of- and gain-of- function of C19orf10 was performed to investigate the roles of C19orf10 on KIRC cell viability, proliferation, migration and invasion via CCK-8, Edu incorporation and Transwell assays respectively. C19orf10 was overexpressed in KIRC tissues and the elevated C19orf10 expression was closely associated with clinicopathological characteristics of KIRC including histological grade, TNM stage, metastatic status. Silencing C19orf10 significantly suppressed the viability, proliferation, migration and invasion ability, while overexpression of C19orf10 promoted the progression and malignant phenotype in KIRC cells. Furthermore, C19orf10 exerted its carcinogenic function by regulating ZO-1 and PTEN/Akt signaling pathway. Moreover, the Kaplan–Meier survival analysis, Cox regression analysis and receiver operating curve analysis showed that patients with C19orf10 overexpression have poor survival time. C19orf10 could discriminate KIRC patients with high-risk from low-risk. Taken together, C19orf10 contributes to KIRC development via ZO-1 and PTEN/Akt signaling pathway and C19orf10 could serve as a potential diagnostic and prognostic candidate and therapeutic target of KIRC.

scholarly journals Integrated analysis of the underlying immunomodulator and survival signature of STON1 gene in kidney renal clear cell carcinoma

2021 ◽  
Author(s):  
Axiu Zheng ◽  
Jianrong Bai ◽  
Yanping Ha ◽  
Bingshu Wang ◽  
Yuan Zou ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Risk Score ◽  
Immune Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Clinicopathological Characteristics ◽  
Risk Scores ◽  
Integrated Analysis

Abstract Background Stonin 1 (STON1) is an endocytic protein but its role in cancer remains unclear. Here, we investigated the role of STON1 in kidney renal clear cell carcinoma (KIRC). Methods We undertook bioinformatics analyses of a series of public databases to determine the expression and clinical significance of STON1 in KIRC and focused on STON1-related immunomodulator and survival signatures. A nomogram model integrating clinicopathological characteristics and risk scores for KIRC was established and validated. Results Through TGCA and GEO databases, STON1 mRNA was found to be significantly downregulated in KIRC compared with normal controls, and decreased STON1 was related to grade, TNM stage, distant metastasis, and vital status of KIRC. Furthermore, OncoLnc, UALCAN, Kaplan–Meier, and GEPIA2 analyses supported that KIRC patients with high STON1 expression had better overall survival. STON1 was positively associated with mismatch proteins including MLH1, PMS2, MSH2, MSH6 and EpCAM, and was negatively correlated with tumor mutational burden. Interestingly, arm-level deletion of STON1 was clearly related to the abundance of immune cells and the infiltration abundance in the majority of 26 immune cell types that were positively related to STON1 mRNA level in the TIMER database. The TISIDB database revealed 21 immunostimulators and 10 immunoinhibitors that were obviously related to STON1 in KIRC. In univariate and multivariate Cox regression analyses, CTLA4 , KDR , LAG3 , PDCD1 , HHLA2 , TNFRSF25 , and TNFSF14 were screened to establish a risk score model, and the low-risk group had a better prognosis for KIRC. Furthermore, a nomogram integrating clinicopathological characteristics and risk score had better accuracy and practicability in predicating the survival of KIRC patients. Conclusions Decreased STON1 expression in KIRC leads to clinical progression and poor survival. Mechanically, loss of STON1 is associated with the aberrant immune microenvironment in KIRC. Integrated clinicopathological characteristics and risk score derived from STON1 -related immunomodulators can aid the prediction of KIRC survival.

scholarly journals Identification of miRNA signatures for kidney renal clear cell carcinoma using the tensor-decomposition method

2019 ◽  
Author(s):  
Ka-Lok Ng ◽  
Y-h Taguchi
Keyword(s):  
Feature Extraction ◽  
Cell Carcinoma ◽  
Complex Disease ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Expression Profiles ◽  
Tensor Decomposition ◽  
Renal Clear Cell Carcinoma ◽  
Integrated Analysis ◽  
Unsupervised Feature Extraction

AbstractCancer is a highly complex disease caused by multiple genetic factors. MicroRNA (miRNA) and mRNA expression profiles are useful for identifying prognostic biomarkers for cancer. Kidney renal clear cell carcinoma (KIRC), which accounts for more than 70% of all renal malignant tumour cases, was selected for our analysis.Traditional methods of identifying cancer prognostic markers may not be accurate. Tensor decomposition (TD) is a useful method uncovering the underlying low-dimensional structures in the tensor. The TD-based unsupervised feature extraction method was applied to analyse mRNA and miRNA expression profiles. Biological annotations of the prognostic miRNAs and mRNAs were examined utilizing the pathway and oncogenic signature databases DIANA-miRPath and MSigDB.TD identified the miRNA signatures and the associated genes. These genes were found to be involved in cancer-related pathways, and 23 genes were significantly correlated with the survival of KIRC patients. We demonstrated that the results are robust and not highly dependent upon the databases we selected. Compared with traditional supervised methods tested, TD achieves much better performance in selecting prognostic miRNAs and mRNAs.These results suggest that integrated analysis using the TD-based unsupervised feature extraction technique is an effective strategy for identifying prognostic signatures in cancer studies.

Abstract 3438: Integrated analysis of germline and somatic variants in renal clear cell carcinoma

2014 ◽  
Author(s):  
Jiayin Wang ◽  
Charles Lu ◽  
Mingchao Xie ◽  
Piyush Tripathi ◽  
Michael McLellan ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Integrated Analysis

Hypoxia regulates the sperm associated antigen 4 (SPAG4) via HIF, which is expressed in renal clear cell carcinoma and promotes migration and invasion in vitro

2013 ◽  
Vol 53 (12) ◽  
pp. 970-978 ◽  
Author(s):  
Karl Xaver Knaup ◽  
Juliana Monti ◽  
Thomas Hackenbeck ◽  
Tilmann Jobst‐Schwan ◽  
Bernd Klanke ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Migration And Invasion

scholarly journals Downregulation of PPA2 expression correlates with poor prognosis of kidney renal clear cell carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12086
Author(s):  
Wenbiao Zhu ◽  
Huiming Jiang ◽  
Shoucheng Xie ◽  
Huanqin Xiao ◽  
Qinghua Liu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Survival Data ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
External Validation ◽  
Renal Clear Cell Carcinoma ◽  
Gene Set Enrichment Analysis ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis

Background Kidney renal clear cell carcinoma (KIRC) is the most common subtype of kidney cancer. Inorganic pyrophosphatase (PPA2) is an enzyme that catalyzes the hydrolysis of pyrophosphate to inorganic phosphate; few studies have reported its significance in cancers. Therefore, we aimed to explore the prognostic value of PPA2 in KIRC. Methods PPA2 expression was detected via immunohistochemistry in a tissue chip containing specimens from 150 patients with KIRC. We evaluated the correlation between PPA2 expression, clinicopathological characteristics, and survival. Data from online databases and another cohort (paraffin-embedded specimens from 10 patients with KIRC) were used for external validation. Results PPA2 expression was significantly lower in KIRC tissues than in normal renal tissues (p < 0.0001). Low expression of PPA2 was significantly associated with a high histologic grade and poor prognosis. The differential expression of PPA2 was validated at the gene and protein levels. Multivariate Cox regression analysis showed that PPA2 expression was an independent prognostic factor in patients with KIRC. Gene set enrichment analysis suggested that decreased expression of PPA2 might be related to the epithelial-mesenchymal transition in KIRC. Conclusions Our study demonstrated that PPA2 is an important energy metabolism-associated biomarker correlated with a favorable prognosis in KIRC.

scholarly journals Inhibition of KIF20A by Transcription Factor IRF6 Affects the Progression of Renal Clear Cell Carcinoma

2020 ◽  
Author(s):  
Xinwei Ma ◽  
Xiaoqi Wang ◽  
Qian Dong ◽  
Hongquan Pang ◽  
Jianming Xu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Carcinoma ◽  
Renal Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Cell Activity ◽  
Renal Clear Cell Carcinoma ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
And Migration

Abstract Background: Renal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, and its incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, but the expression of IRF6 in ccRCC has not been reported so far.Methods: The expression of IRF6 and KIF20A in ccRCC was predicted by GEPIA and HAP database. In addition, the GEPIA database predicted the relationship between the expression of IRF6 and KIF20A and the pathological staging, overall survival, and disease-free survival of ccRCC. The possible binding sites of IRF6 and KIF20A promoters were predicted by JASPAR database and verified by luciferase and ChIP experiments. The specific effects of IRF6 on proliferation invasion and apoptosis of ccRCC were subsequently examined at the cellular level. The expression of IRF6 and KIF20A in ccRCC cell lines was detected by RT-qPCR and western blot. Cell transfection techniques were used to construct IRF6 and KIF20A overexpressed or interfering plasmids. CCK-8 and clone formation assays were used to detect cell activity. Apoptosis was detected by TUNEL assay. Wound healing and Transwell assays detected the ability of cell migration and invasion, respectively.Results: The database predicted that IRF6 expression was down-regulated in renal carcinoma tissues and correlated with poor prognosis. Cell experiments showed that overexpression of IRF6 inhibited proliferation, invasion and migration of ccRCC. In addition, the database predicted that KIF20A was up-regulated in renal carcinoma tissues and associated with prognosis, and cell experiments demonstrated that interference with KIF20A inhibited proliferation, invasion, and migration of ccRCC. Finally, we confirmed that KIF20A is a functional target of IRF6, and KIF20A partially reverses the effects of IRF6 on the proliferation, invasion and migration of ccRCC.Conclusion: Inhibition of KIF20A by transcription factor IRF6 affects the cell proliferation, invasion, migration of renal clear cell carcinoma.

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