PD12-01 DOES CO-MEDICATION WITH NON-ANTICANCER DRUGS AFFECT OUTCOMES IN PATIENTS WITH SURGICALLY TREATED CLEAR CELL RENAL CELL CARCINOMA ? - EVALUATION OF SURVIVAL, CELL-CYCLE ACTIVITY, AND PROLIFERATION

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.

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MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis

Oncotarget ◽

10.18632/oncotarget.3915 ◽

2015 ◽

Vol 6 (15) ◽

pp. 13201-13215 ◽

Cited By ~ 28

Author(s):

Haibing Xiao ◽

Jin Zeng ◽

Heng Li ◽

Ke Chen ◽

Gan Yu ◽

...

Keyword(s):

Cell Cycle ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Cell Cycle Regulation ◽

Clear Cell ◽

Poor Survival ◽

Cell Renal Cell Carcinoma ◽

Cycle Regulation

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

Cellular Physiology and Biochemistry ◽

10.1159/000491957 ◽

2018 ◽

Vol 48 (3) ◽

pp. 891-904 ◽

Cited By ~ 27

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.

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

Cancer Biomarkers ◽

10.3233/cbm-150530 ◽

2015 ◽

Vol 15 (6) ◽

pp. 861-867 ◽

Cited By ~ 9

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

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

Cancer Letters ◽

10.1016/j.canlet.2016.01.032 ◽

2016 ◽

Vol 374 (1) ◽

pp. 107-116 ◽

Cited By ~ 31

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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RASSF6promotes p21Cip1/Waf1-dependent cell cycle arrest and apoptosis through activation of the JNK/SAPK pathway in clear cell renal cell carcinoma

Cell Cycle ◽

10.4161/cc.28416 ◽

2014 ◽

Vol 13 (9) ◽

pp. 1440-1449 ◽

Cited By ~ 13

Author(s):

Ying-Ying Liang ◽

Li-Sheng Zheng ◽

Yuan-Zhong Wu ◽

Li-Xia Peng ◽

Yun Cao ◽

...

Keyword(s):

Cell Cycle ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Cycle Arrest ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Cycle Arrest ◽

Dependent Cell

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miR-129-5p inhibits clear cell renal cell carcinoma cell proliferation, migration and invasion by targeting SPN

Cancer Cell International ◽

10.1186/s12935-021-01820-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Bin Gao ◽

Lijuan Wang ◽

Na Zhang ◽

Miaomiao Han ◽

Yubo Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Luciferase Assay ◽

Cell Renal Cell Carcinoma ◽

Regulated Expression ◽

Ccrcc Cell

Abstract Objective Our study aims to investigate the mechanism of the miR-129-5p/SPN axis in clear cell renal cell carcinoma (ccRCC), providing a novel direction for the targeted therapy of ccRCC. Methods Bioinformatics methods were implemented to find the differentially expressed genes (DEGs) associated with ccRCC from TCGA database. qRT-PCR was performed to detect miR-129-5p and SPN mRNA expression, while western bot was carried out for the detection of protein expression of SPN. Bioinformatics analysis was used to predict the binding sites of miR-129-5p on SPN 3’UTR, while dual-luciferase assay was conducted to verify their binding relationship. CCK-8 assay, colony formation assay, wound healing assay and Transwell assay were employed to measure ccRCC cell proliferative ability, cell formation ability, cell migratory and invasive abilities. Flow cytometry was implemented to assess cell cycle and apoptosis. Results miR-129-5p exhibited a significantly down-regulated expression level in ccRCC, while SPN showed a remarkably up-regulated expression level. Overexpressed miR-129-5p inhibited ccRCC cell proliferative, invasive and migratory capacities while induced cell cycle arrest in G0/G1 phase and promoted cell apoptosis. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Moreover, overexpressed miR-129-5p remarkably reduced SPN expression in cancer cells, weakened the promoting effect of SPN on cell proliferation, migration, invasion and cell cycle progress, and led to enhanced cell apoptotic activity. Conclusions Our study proves the regulatory effect of the miR-129-5p/SPN axis in ccRCC, and provides a novel potential target for precise treatment of patients with ccRCC.

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Downregulation of the negative cell cycle regulator BTG2 is common in clear cell renal cell carcinoma

Pathology - Research and Practice ◽

10.1016/s0344-0338(04)80490-4 ◽

2004 ◽

Vol 200 (4) ◽

pp. 277

Author(s):

K. Struckmann ◽

P. Schraml ◽

R. Simon ◽

K. Elmen-Horst ◽

M. Mirlacher ◽

...

Keyword(s):

Cell Cycle ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Negative Cell ◽

Cell Cycle Regulator

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miR-129-5p inhibits clear cell renal cell carcinoma cell proliferation, migration and invasion by targeting SPN

10.21203/rs.3.rs-38613/v3 ◽

2021 ◽

Author(s):

Bin Gao ◽

Lijuan Wang ◽

Yubo Zhang ◽

Na Zhang ◽

Miaomiao Han ◽

...

Keyword(s):

Cell Cycle ◽

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Luciferase Assay ◽

Cell Renal Cell Carcinoma ◽

Regulated Expression ◽

Ccrcc Cell

Abstract Objective: Our study aims to investigate the mechanism of the miR-129-5p/SPN axis in clear cell renal cell carcinoma (ccRCC), providing a novel direction for the targeted therapy of ccRCC. Methods: Bioinformatics methods were implemented to find the differentially expressed genes (DEGs) associated with ccRCC from TCGA database. qRT-PCR was performed to detect miR-129-5p and SPN mRNA expression, while western bot was carried out for the detection of protein expression of SPN. Bioinformatics analysis was used to predict the binding sites of miR-129-5p on SPN 3’UTR, while dual-luciferase assay was conducted to verify their binding relationship. CCK-8 assay, colony formation assay, wound healing assay and Transwell assay were employed to measure ccRCC cell proliferative ability, cell formation ability, cell migratory and invasive abilities. Flow cytometry was implemented to assess cell cycle and apoptosis. Results: miR-129-5p exhibited a significantly down-regulated expression level in ccRCC, while SPN showed a remarkably up-regulated expression level. Overexpressed miR-129-5p inhibited ccRCC cell proliferative, invasive and migratory capacities while induced cell cycle arrest in G0/G1 phase and promoted cell apoptosis. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Moreover, overexpressed miR-129-5p remarkably reduced SPN expression in cancer cells, weakened the promoting effect of SPN on cell proliferation, migration, invasion and cell cycle progress, and led to enhanced cell apoptotic activity.Conclusion: Our study proves the regulatory effect of the miR-129-5p/SPN axis in ccRCC, and provides a novel potential target for precise treatment of patients with ccRCC.

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