scholarly journals SREBP1 site 1 protease inhibitor PF-429242 suppresses renal cell carcinoma cell growth

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Tong-bing Wang ◽  
Mei Geng ◽  
Hua Jin ◽  
Ai-guo Tang ◽  
Hao Sun ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Regulatory Element ◽  
Severe Combined Immunodeficiency ◽  
Migration And Invasion ◽  
Amino Terminal ◽  
Xenograft Growth

AbstractRenal cell carcinoma (RCC) cells have increased lipogenesis and cholesterol synthesis. Sterol regulatory element-binding protein-1 (SREBP1) is cleaved by site 1 protease (S1P) to release the transcriptionally active amino-terminal domain. PF-429242 is a potent and competitive S1P inhibitor. We here tested its activity in RCC cells. In established and primary human RCC cells, PF-429242 potently inhibited cell proliferation, migration, and invasion. The S1P inhibitor provoked apoptosis activation in RCC cells. Furthermore, shRNA-mediated S1P silencing or CRISPR/Cas9-induced S1P knockout led to RCC cell growth inhibition and apoptosis activation. Conversely, ectopic overexpression of SREBP1 or S1P augmented RCC cell proliferation and migration. Daily i.v. injection of a single dose of PF-429242 robustly inhibited RCC xenograft growth in severe combined immunodeficiency mice. Additionally, intratumoral injection of S1P shRNA lentivirus inhibited RCC xenograft growth in mice. SREBP1, S1P, and its target gene low density lipoprotein receptor (LDLR) were significantly elevated in human RCC tissues. These results suggest that targeting S1P by PF-429242 inhibited RCC cell growth in vitro and in vivo.

The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion

Tumor Biology ◽  
2016 ◽  
Vol 37 (9) ◽  
pp. 12823-12831 ◽  
Author(s):  
Ji-Gen Ping ◽  
Fei Wang ◽  
Jin-Xian Pu ◽  
Ping-Fu Hou ◽  
Yan-Su Chen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Cancer Cell ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation

scholarly journals CORO6 Promotes Cell Growth and Invasion of Clear Cell Renal Cell Carcinoma via Activation of WNT Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinjun Wang ◽  
Yiming Xiao ◽  
Si Li ◽  
Zhijian Yan ◽  
Guangcheng Luo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Growth ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumor Biology ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Migration And Invasion

Renal cell carcinoma (RCC) constitutes the most lethal type of genitourinary cancer. Understanding of RCC tumor biology helps to identify novel targets and develop directed treatments for patients with this type of cancer. Analysis from both The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset and our RCC samples demonstrated that the expression level of CORO6 was significantly higher in RCC patients than in normal kidney tissues, and its level was highly associated with tumor stage and grade. Importantly, CORO6 expression level was an independent predictor of tumor metastasis and overall survival in RCC patients. Our cell line data also confirmed that CORO6 knockdown could suppress RCC cell growth as well as cell migration and invasion. The depletion of CORO6 led to cell cycle arrest at the G0/G1 phase and caused cell apoptosis. Further, mechanistic dissection showed that CORO6 mediated RCC cell growth, and cell invasion relied on WNT signaling. Moreover, the in vivo data suggested that CORO6 knockdown indeed suppressed RCC tumor growth. Overall, our study defines the oncogenic role of CORO6 in RCC progression and provides a rationale for developing CORO6-targeted therapies for improved treatment of RCC patients.

scholarly journals Interleukin-33 Predicts Poor Prognosis and Promotes Renal Cell Carcinoma Cell Growth Through its Receptor ST2 and the JNK Signaling Pathway

2018 ◽  
Vol 47 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Chang-wen Wu ◽  
Yi-guo Wu ◽  
Cheng Cheng ◽  
Zheng-dong Hong ◽  
Zi-min Shi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Flow Cytometry ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cell Carcinoma ◽  
Western Blotting ◽  
Renal Cell ◽  
Jnk Signaling

Background/Aims: Renal cell carcinoma (RCC) is currently the ninth most common cancer in men. Interleukin (IL)-33 expression has previously been associated with a number of cancers; however, its biological role in RCC is poorly understood. In this study, we sought to elucidate the role of IL-33 in RCC. Methods: Serum IL-33 levels were measured by ELISA. IL-33 expression in clinical RCC samples was examined by immunocytochemistry. The proliferation and apoptosis rate of RCC were determined by CCK8 and flow cytometry. Mcl1 and Bcl-2 expression were measured by quantitative real-time PCR and western blotting. JNK expression were measured by western blotting and flow cytometry. The in vivo role of IL-33 in RCC tumorigenesis was examined by animal models. Results: We found that increased expression of IL-33 in RCC was associated with tumor-lymph node-metastasis (TNM) stage and inversely correlated with prognosis. IL-33 enhances RCC cell growth in vivo and stimulates RCC cell proliferation and prevents chemotherapy-induced tumor apoptosis in vitro. Furthermore, we demonstrated that IL-33 promotes RCC cell proliferation and chemotherapy resistance via its receptor ST2 and the JNK signaling activation in tumor cells. Conclusion: Our findings suggest that targeting IL-33/ST2 and JNK signaling may have potential value in the treatment of RCC.

scholarly journals LncRNA POU3F3 Promotes Cancer Cell Proliferation, Migration, and Invasion in Renal Cell Carcinoma by Downregulating LncRNA GAS5

2021 ◽  
pp. 1-7
Author(s):  
Lei Zhang ◽  
Cezheng Wang ◽  
Min Ma
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
In Situ Hybridization ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Tumor Tissues ◽  
Lncrna Gas5

<b><i>Background:</i></b> LncRNAs play regulatory roles in diverse nephrological disorders, including renal cancer. Overexpression of lncRNA POU3F3 (POU3F3) has only been reported in esophageal squamous-cell carcinomas, indicating POU3F3 may be an oncogene in this disease. LncRNA GAS5 (GAS5) was reported to be a suppressor in various tumors. However, the roles and underlying mechanism of POU3F3 and GAS5 involved in renal cell carcinoma (RCC) remain unknown. <b><i>Methods:</i></b> Real-time quantitative PCR and in situ hybridization were performed to determine the expression of POU3F3 and GAS5 in paired tumor and adjacent healthy tissues donated by 68 RCC patients. The prognostic values of POU3F3 and GAS5 for RCC were analyzed by performing a 5-year follow-up study. Overexpression of POU3F3 and GAS5 was achieved in RCC cells to explore the interactions between them. Transwell assay and cell proliferation assay were performed to evaluate the role of POU3F3 and GAS5 in regulating RCC cell proliferation, migration, and invasion. <b><i>Results:</i></b> In the present study, we found that POU3F3 was upregulated while GAS5 was downregulated in tumor tissues than that in adjacent healthy tissues of patients with RCC. In situ hybridization analysis showed that POU3F3 was mostly expressed in tumor tissues, while GAS5 was mostly expressed in adjacent healthy tissues. High level of POU3F3 and low level of GAS5 were closely correlated with poor prognosis of RCC patients. Expression levels of POU3F3 and GAS5 were significantly and inversely correlated in tumor tissues but not in adjacent healthy tissues of RCC patients. Overexpression of POU3F3 mediated the downregulation of GAS5 in RCC cells, while GAS5 overexpression failed to significantly affect POU3F3 expression. Overexpression of POU3F3 led to promoted, while GAS5 overexpression led to inhibited proliferation, migration, and invasion of RCC cells. In addition, GAS5 overexpression attenuated the enhancing effects of POU3F3 overexpression on cancer cell proliferation, migration, and invasion. <b><i>Conclusion:</i></b> POU3F3 promoted cell proliferation, migration, and invasion in RCC possibly by downregulating GAS5.

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

2020 ◽  
Author(s):  
Bin Gao ◽  
Lijuan Wang ◽  
Yubo Zhang ◽  
Na Zhang ◽  
Miaomiao Han ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
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. 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. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Additionally, overexpressing miR-129-5p markedly reduced SPN expression in tumor cells, and attenuated the promoting effect of SPN on cell proliferation, migration and invasion. 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.

scholarly journals Ubenimex inhibits cell proliferation, migration and invasion in renal cell carcinoma: The effect is autophagy-associated

2014 ◽  
Vol 33 (3) ◽  
pp. 1372-1380 ◽  
Author(s):  
SHUAI LIU ◽  
FANG XIE ◽  
HAFENG WANG ◽  
ZHENG LIU ◽  
XIAOWEN LIU ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Migration And Invasion
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