scholarly journals mTORC2 mediate FLCN-induced HIF2α nuclear import and proliferation of clear cell renal cell carcinoma

2020 ◽  
Author(s):  
Xuyang Zhao ◽  
Yadong Ma ◽  
Jie Cui ◽  
Haiyang Zhao ◽  
Lei Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Molecular Mechanism ◽  
Renal Cancer ◽  
Cancer Progression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
And Migration

AbstractClear cell renal cell carcinoma (ccRCC), as the most important type of renal carcinoma, has a high incidence and easy metastasis. Folliculin (FLCN) was identified as a tumor suppressor gene. Its deletions and mutations are associated with a potential risk of kidney cancer. At present, the specific molecular mechanism of FLCN-induced proliferation, invasion and migration in clear cell renal cell carcinoma remains elusive.In this study, we demonstrated that FLCN controled cell proliferation, invasion and migration through PI3K/mTORC2 pathway. FLCN combined with HIF2α in various normal and cancerous renal cells, and mTORC2 mediate FLCN effectively alleviated the deterioration of renal cancer cells by degrading HIF2α. Silencing of FLCN showed promotion of HIF2α protein expression, which in turn led to an increase in downstream target genes Cyclin D1 and MMP9. Moreover, when interfering with siFLCN, HIF2α degradation rate was delayed, and the time of entry into the nucleus was advanced. Taken together, our study illustrated that mTORC2 promoted the specific molecular mechanism of HIF2α by down-regulated FLCN, and might be a new therapeutic target against renal cancer progression.

scholarly journals Overexpression of Spondin-2 Is Associated with Recurrence-Free Survival in Patients with Localized Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Hui-Min Ma ◽  
Meng Yu ◽  
Cong Wu ◽  
Hou-Bao Huang ◽  
Ya-Wei Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Recurrence Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival ◽  
Invasion And Migration ◽  
And Migration

Background. The spondin-2 (SPON2) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in clear cell renal cell carcinoma (ccRCC) are still unclear. Methods. SPON2 expression in ccRCC was evaluated using expression data from TCGA and GEO databases, then confirmed by local patient population (94 patients). The clinical significance of SPON2 expression was evaluated. Downregulation of SPON2 was performed using small-interfering RNA (siRNA). The effects of SPON2 silencing on cell proliferation, apoptosis, invasion, and migration in vitro were investigated. Results. SPON2 was overexpressed in the majority of the ccRCC at both mRNA and protein levels. SPON2 expression was significantly correlated with stage, grade, and recurrence (all P<0.05) in patients with localized ccRCC. The receiver operating characteristic (ROC) curve showed that SPON2 expression could serve as a predictor of recurrence. SPON2 expression was significantly associated with recurrence-free survival (RFS) in patients with localized ccRCC. Knocking down SPON2 resulted in suppressed cell invasion and migration in vitro. Conclusion. SPON2 expression might function as a prognostic biomarker in patients with localized ccRCC.

Effect of EH domain containing protein 2 on the biological behavior of clear cell renal cell carcinoma

2019 ◽  
Vol 38 (8) ◽  
pp. 927-937 ◽  
Author(s):  
C Liu ◽  
S Liu ◽  
L Wang ◽  
Y Wang ◽  
Y Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Control Group ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
Eh Domain ◽  
And Migration

To investigate the effects of EH domain containing protein 2 (EHD2) on clear cell renal cell carcinoma (ccRCC) and provide new insights for the clinical treatment of rental cancer. Forty patients (26 males and 14 females, 62.4 ± 5.7 years old) with ccRCC were selected from January 2015 to December 2016 to serve as research subjects in this study. The EHD2 protein expression in the tumor tissues and adjacent healthy tissues of ccRCC patients were detected by Western Blot assay. The cells of ccRCC cell lines RLC-310 and 786-O were divided into normal control group (control), no-load control group (pLV), EHD2 overexpression group (pLV-EHD2), and EHD2 interference group (pLV-siEHD2). The expression levels of EHD2 protein in each group of cells were detected by western blot. The cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. Wound healing assay was performed to check the cell migration ability. Transwell invasion assay was used to detect the cell invasion ability. Cell apoptosis was detected by flow cytometry. The expression level of EHD2 was significantly increased in pLV-EHD2 group and decreased in pLV-siEHD2 group compared with control group and pLV-siEHD2 group, indicating the successfully established EHD2 overexpression cell line and EHD2 RNA interference cell line. EHD2 overexpression enhanced the proliferation, invasion, and migration but inhibited the apoptosis of ccRCC cells, while EHD2 interference showed opposite functions. EHD2 interference can inhibit the development of ccRCC by inhibiting the proliferation, invasion, and migration, and EHD2 can potentially serve as a molecular target for the clinical treatment of ccRCC.

scholarly journals Downregulation of miR-335 exhibited an oncogenic effect via promoting KDM3A/YAP1 networks in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Wenqiang Zhang ◽  
Ruiyu Liu ◽  
Lin Zhang ◽  
Chao Wang ◽  
Ziyan Dong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Survival Rate ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
Downstream Target ◽  
Localized Disease ◽  
And Migration

AbstractClear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer affecting many people worldwide. Although the 5-year survival rate is 65% in localized disease, after metastasis, the survival rate is <10%. Emerging evidence has shown that microRNAs (miRNAs) play a crucial regulatory role in the progression of ccRCC. Here, we show that miR-335, an anti-onco-miRNA, is downregulation in tumor tissue and inhibited ccRCC cell proliferation, invasion, and migration. Our studies further identify the H3K9me1/2 histone demethylase KDM3A as a new miR-335-regulated gene. We show that KDM3A is overexpressed in ccRCC, and its upregulation contributes to the carcinogenesis and metastasis of ccRCC. Moreover, with the overexpression of KDM3A, YAP1 was increased and identified as a direct downstream target of KDM3A. Enrichment of KDM3A demethylase on YAP1 promoter was confirmed by CHIP-qPCR and YAP1 was also found involved in the cell growth and metastasis inhibitory of miR-335. Together, our study establishes a new miR-335/KDM3A/YAP1 regulation axis, which provided new insight and potential targeting of the metastasized ccRCC.

scholarly journals Upregulation of homeobox D10 expression suppresses invasion and migration of clear cell renal cell carcinoma through targeting of E-cadherin

2021 ◽  
Author(s):  
Zongtao Ren ◽  
Yunfeng Niu ◽  
Bo Fan ◽  
Aili Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Luciferase Reporter ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
And Migration ◽  
E Cadherin

Abstract Background Clear cell renal cell carcinoma (CCRCC) is one of the most common types of renal cell carcinoma. Accumulating evidence indicates that homeobox D10 (HOXD10) acts as a tumor suppressor or oncogene in various carcinomas. However, the regulation and potential mechanisms of HOXD10 in CCRCC remain largely unknown. Purpose To explore the effect and potential mechanism of HOXD10 on the invasion and migration of CCRCC cells. Methods The expression of HOXD10, E-cadherin and other epithelial mesenchymal transition (EMT)-related proteins was assessed by reverse transcription-quantitative real-time PCR (qRT-PCR) and Western blots. A series of functional assays were performed in RCC cell lines to explore the function of HOXD10 in CCRCC progression. Bioinformatics analysis, ChIP assays, and dual luciferase reporter assays were utilized to identify the interaction between HOXD10 and E-cadherin. Results Low expression of HOXD10 and E-cadherin was observed in CCRCC tissues and ACHN and 786-O cells. Downregulation of HOXD10 expression was correlated with the TNM stage of CCRCC patients. Functional experiments demonstrated that malignant biological ability was significantly inhibited by HOXD10 overexpression in RCC cells. Moreover, E-cadherin was a potential target gene of HOXD10, as evidenced by a series of assays. In addition, overexpression of HOXD10 inhibited the progression of CCRCC by regulating the expression of E-cadherin, vimentin, and β-catenin in vitro. Conclusion HOXD10 acts as a tumor suppressor and suppresses invasion and migration of CCRCC cells by regulating E-cadherin and EMT processes. Thus, targeting HOXD10 may be a therapeutic strategy for CCRCC treatment.

scholarly journals HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Swathi Ramakrishnan ◽  
ShengYu Ku ◽  
Eric Ciamporcero ◽  
Kiersten Marie Miles ◽  
Kris Attwood ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Invasion ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
And Migration

scholarly journals MicroRNA-30e-3p inhibits cell invasion and migration in clear cell renal cell carcinoma by targeting Snail1

2017 ◽  
Vol 13 (4) ◽  
pp. 2053-2058 ◽  
Author(s):  
Daya Wang ◽  
Chao Zhu ◽  
Yifan Zhang ◽  
Yuenan Zheng ◽  
Feiju Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Invasion ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
And Migration

scholarly journals FKBP51 promotes invasion and migration by increasing the autophagic degradation of TIMP3 in clear cell renal cell carcinoma

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Shaowei Mao ◽  
Di Zhang ◽  
Luan Chen ◽  
Jie Tan ◽  
Yunpeng Chu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Cell Renal Cell Carcinoma ◽  
Invasion And Migration ◽  
Autophagic Degradation ◽  
And Migration

AbstractThe occurrence of metastasis is a serious risk for renal cell carcinoma (RCC) patients. In order to develop novel therapeutic approaches to control the progression of metastatic RCC, it is of urgent need to understand the molecular mechanisms underlying RCC metastasis and identify prognostic markers of metastatic risk. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been known to be closely associated with extracellular matrix (ECM) turnover, which plays a highly active role in tumor metastasis. Recent studies have shown that immunophilin FK-506-binding protein 51 (FKBP51) may be important for the regulation of ECM function, and exert effects on the invasion and migration of tumor cells. However, the mechanisms underlying these activities remain unclear. The present study detected the role of FKBP51 in clear cell renal cell carcinoma (ccRCC), the most common subtype of RCC, and found that FKBP51 significantly promotes ccRCC invasion and migration by binding with the TIMP3, connecting TIMP3 with Beclin1 complex and increasing autophagic degradation of TIMP3. Given the important roles that TIMPs/MMPs play in ECM regulation and remodeling, our findings will provide new perspective for future investigation of the regulation of metastasis of kidney cancer and other types of cancer.

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