scholarly journals Cell cycle progression score predicts metastatic progression of clear cell renal cell carcinoma after resection

2015 ◽  
Vol 15 (6) ◽  
pp. 861-867 ◽  
Author(s):  
Eric J. Askeland ◽  
Vincent A. Chehval ◽  
Ryan W. Askeland ◽  
Placede G. Fosso ◽  
Zaina Sangale ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Cycle Progression ◽  
Clear Cell ◽  
Metastatic Progression ◽  
Cell Renal Cell Carcinoma ◽  
Cycle Progression

scholarly journals The role of CRP and ATG9B expression in clear cell renal cell carcinoma

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Zheng Ma ◽  
Zengguang Qi ◽  
Zhengfei Shan ◽  
Jiangsong Li ◽  
Jing Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Distant Metastasis ◽  
Renal Cell ◽  
Cell Cycle Progression ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cycle Progression ◽  
Ccrcc Cell

The purpose of the study is to investigate the correlation between the expression of C-reactive protein (CRP) and autophagy-related 9B (ATG9B) and pathological features of clear cell renal cell carcinoma (CCRCC) patients. We also intended to explore the effects of manipulated expression of CRP and ATG9B on the apoptosis and cell cycle progression of CCRCC cell line. ATG9B expression in CCRCC tissues and adjacent renal tissues was analyzed by immunohistochemistry (IHC). Gene expression was determined at transcription and translational levels using real-time quantitative PCR (RT-qPCR) and Western blot. The association between CRP/ATG9B expression and clinical-pathological parameters including age, gender, pathological grades, TNM stage and distant metastasis of the patients was assessed by correlation analysis. siRNA and overexpression plasmids construction were used to manipulate the expression of CRP in human CCRCC cell line 786-O. Cell apoptosis and cell cycle progression were determined using flow cytometry (FCM) and Hoechst 33258 staining. CRP expression correlates with ATG9B expression. The expression of CRP and ATG9B are significantly correlated with TNM staging, distant metastasis, and survival time of CCRCC patients. A high-level of CRP indicates a poor overall survival (OS). In addition, CRP expression influences cell cycle and apoptosis of CCRCC cells. The study reveals that CRP might be a CCRCC development promoter. In addition, there is a close relationship between CRP and ATG9B in CCRCC carcinogenesis.

scholarly journals LncRNA-LET inhibits cell growth of clear cell renal cell carcinoma by regulating miR-373-3p

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhuo Ye ◽  
Jiachen Duan ◽  
Lihui Wang ◽  
Yanli Ji ◽  
Baoping Qiao
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Luciferase Reporter ◽  
Cell Renal Cell Carcinoma

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with a poor prognosis. LncRNA-LET is a long non-coding RNA (lncRNA) that is down-regulated in ccRCC tissues. However, its role in ccRCC development and progress is unclear. Methods LncRNA-LET expression was detected in ccRCC tissues and ccRCC cells using quantitative real-time PCR. The overexpression and knockdown experiments were performed in ccRCC cells and xenograft mouse model to evaluate role of lncRNA-LET. Cell cycle, apoptosis and JC-1 assays were conducted via flow cytometer. The protein levels were measured through western blot analysis and the interaction between lncRNA-LET and miR-373-3p was identified via luciferase reporter assay. Results LncRNA-LET expression was lower in ccRCC tissues than that in the matched adjacent non-tumor tissues (n = 16). In vitro, lncRNA-LET overexpression induced cell cycle arrest, promoted apoptosis and impaired mitochondrial membrane potential, whereas its knockdown exerted opposite effects. Moreover, we noted that lncRNA-LET may act as a target for oncomiR miR-373-3p. In contrast to lncRNA-LET, miR-373-3p expression was higher in ccRCC tissues. The binding between lncRNA-LET and miR-373-3p was validated. Two downstream targets of miR-373-3p, Dickkopf-1 (DKK1) and tissue inhibitor of metalloproteinase-2 (TIMP2), were positively regulated by lncRNA-LET in ccRCC cells. MiR-373-3p mimics reduced lncRNA-LET-induced up-regulation of DKK1 and TIMP2 levels, and attenuated lncRNA-LET-mediated anti-tumor effects in ccRCC cells. In vivo, lncRNA-LET suppressed the growth of ccRCC xenograft tumors. Conclusion These findings indicate that lncRNA-LET plays a tumor suppressive role in ccRCC by regulating miR-373-3p.

scholarly journals Long Non-Coding RNA LUCAT1 Promotes Proliferation and Invasion in Clear Cell Renal Cell Carcinoma Through AKT/GSK-3β Signaling Pathway

2018 ◽  
Vol 48 (3) ◽  
pp. 891-904 ◽  
Author(s):  
Zaosong Zheng ◽  
Fengjin Zhao ◽  
Dingjun Zhu ◽  
Jinli Han ◽  
Haicheng Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Normal Tissues ◽  
Gsk 3Β ◽  
Proliferation And Invasion

Background/Aims: Long non-coding RNAs (lncRNAs) have emerged as new regulators and biomarkers in several cancers. However, few lncRNAs have been well characterized in clear cell renal cell carcinoma (ccRCC). Methods: We investigated the lncRNA expression profile by microarray analysis in 5 corresponding ccRCC tissues and adjacent normal tissues. Lung cancer–associated transcript 1 (LUCAT1) expression was examined in 90 paired ccRCC tissues by real-time PCR and validated by The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis was used to examine the prognostic value of LUCAT1 and CXCL2 in ccRCC patients. Loss and gain of function were performed to explore the effect of LUCAT1 on proliferation and invasion in ccRCC cells. Western blotting was performed to evaluate the underlying mechanisms of LUCAT1 in ccRCC progression. Chemokine stimulation assay was performed to investigate possible mechanisms controlling LUCAT1 expression in ccRCC cells. Enzyme-linked immunosorbent assays were performed to determine serum CXCL2 in ccRCC patients and healthy volunteers. Receiver operating characteristic curve analysis was performed to examine the clinical diagnostic value of serum CXCL2 in ccRCC. Results: We found that LUCAT1 was significantly upregulated in both clinical ccRCC tissues (n = 90) and TCGA ccRCC tissues (n = 448) compared with normal tissues. Statistical analysis revealed that the LUCAT1 expression level positively correlated with tumor T stage (P < 0.01), M stage (P < 0.01), and TNM stage (P < 0.01). Overall survival and disease-free survival time were significantly shorter in the high-LUCAT1-expression group than in the low-LUCAT1-expression group (log-rank P < 0.01). LUCAT1 knockdown inhibited ccRCC cell proliferation and colony formation, induced cell cycle arrest at G1 phase, and inhibited cell migration and invasion. Overexpression of LUCAT1 promoted proliferation, migration, and invasion of ccRCC cells. Mechanistic investigations showed that LUCAT1 induced cell cycle G1 arrest by regulating the expression of cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma transcriptional corepressor 1. Moreover, LUCAT1 promoted proliferation and invasion in ccRCC cells partly through inducing the phosphorylation of AKT and suppressing the phosphorylation of GSK-3β. We also revealed that chemokine CXCL2, upregulated in ccRCC, induced LUCAT1 expression and might be a diagnostic and prognostic biomarker in ccRCC. Conclusions: LUCAT1 was upregulated in ccRCC tissues and renal cancer cell lines, and significantly correlated with malignant stage and poor prognosis in ccRCC. LUCAT1 promoted proliferation and invasion in ccRCC cells through the AKT/GSK-3β signaling pathway. We also revealed that LUCAT1 overexpression was induced by chemokine CXCL2. These findings indicate that the CXCL2/LUCAT1/AKT/GSK-3β axis is a potential therapeutic target and molecular biomarker for ccRCC.

scholarly journals Dysregulation of the miR-25-IMPA2 axis promotes metastatic progression in clear cell renal cell carcinoma

EBioMedicine ◽  
2019 ◽  
Vol 45 ◽  
pp. 220-230 ◽  
Author(s):  
Yuh-Feng Lin ◽  
Jian-Liang Chou ◽  
Jeng-Shou Chang ◽  
I-Jen Chiu ◽  
Hui-Wen Chiu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Metastatic Progression ◽  
Cell Renal Cell Carcinoma

Cell cycle progression score to predict metastatic progression of clear cell renal cell carcinoma after resection.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 442-442
Author(s):  
Eric J. Askeland ◽  
Vincent A. Chehval ◽  
Ryan W. Askeland ◽  
Zaina Sangale ◽  
Placede Gangnang Fosso ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Size ◽  
Prognostic Value ◽  
Cell Cycle Progression ◽  
Clear Cell ◽  
Univariate Analysis ◽  
Metastatic Progression ◽  
Cell Renal Cell Carcinoma ◽  
Cycle Progression

442 Background: Clear cell renal cell carcinoma (ccRCC) is primarily treated surgically when organ confined, but requires close follow-up to evaluate for recurrence. Expression levels of cell cycle progression (CCP) genes have prognostic value in certain cancers. We evaluated the prognostic value of the CCP expression in surgically resected ccRCC. Methods: Medical records were retrospectively reviewed. Patients with metastasis or lymph node involvement at surgery were excluded. Cases developed metastasis within 5 years of resection; controls were followed for at least 4.5 years without recurrence. Specimens were re-reviewed by a single pathologist. Tumor FFPE slides were macrodissected and RNA extracted. CCP score, sex, age, T stage, Fuhrman Nuclear grade (FNG), tumor size, smoking status, lymphovascular invasion (LVI), and time to metastasis were available for analysis. Univariate and multivariate analyses were used to evaluate association with metastatic progression. Subsequently, the tumor transcriptome was interrogated for other informative biomarkers using next-generation sequencing (NGS). Funding was by Myriad Genetics. Results: Twenty-six cases and 38 controls were evaluated. Median time to metastasis was 1.68 years (IQR 1.06-3.69) for the case group. Median follow-up was 6.69 years for controls. Univariate analysis revealed that LVI (OR 4.64, p=0.005), FNG (OR 4.16, p=0.0099) and CCP score (OR 2.65, p=0.0091) were significantly associated with progression to metastasis. In multivariate analysis, age (p=0.026), tumor size (p=0.022) and CCP score (p=0.026) were statistically significant. A step-wise multivariate model including age, CCP, tumor size and LVI had an AUC of 0.84, which decreased to 0.78 if CCP score was excluded. CCP scores calculated by qPCR and NGS were correlated (rho = 0.91). However, no other genes showed a significant association with metastasis or TNM stage (after correcting for multiple testing) in univariate analysis or after adjusting for CCP score. Conclusions: The cell cycle progression score predicts metastatic progression after resection of ccRCC and appears to add significant prognostic information to standard clinical and pathological variables.

miR-206 functions as a novel cell cycle regulator and tumor suppressor in clear-cell renal cell carcinoma

2016 ◽  
Vol 374 (1) ◽  
pp. 107-116 ◽  
Author(s):  
Haibing Xiao ◽  
Wei Xiao ◽  
Jing Cao ◽  
Heng Li ◽  
Wei Guan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cell Cycle Regulator
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