Everolimus suppresses invasion and migration of renal cell carcinoma by inhibiting FAK activity and reversing epithelial to mesenchymal transition in vitro and in vivo

2017 ◽  
Vol 32 (7) ◽  
pp. 1888-1898 ◽  
Author(s):  
Sheng-Wen Wu ◽  
Pei-Ni Chen ◽  
Chin-Yin Lin ◽  
Yih-Shou Hsieh ◽  
Horng-Rong Chang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

scholarly journals Kinesin Motor Protein KIFC1 Is a Target Protein of miR-338-3p and Is Associated With Poor Prognosis and Progression of Renal Cell Carcinoma

2018 ◽  
Vol 27 (1) ◽  
pp. 125-137 ◽  
Author(s):  
Gang Li ◽  
Tie Chong ◽  
Jie Yang ◽  
Hongliang Li ◽  
Haiwen Chen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Therapeutic Target ◽  
Renal Cell ◽  
Critical Role ◽  
Survival Prognosis ◽  
Inhibition Of Proliferation ◽  
Invasion And Migration

KIFC1 (kinesin family member C1) plays a critical role in clustering of extra centrosomes in various cancer cells and thus could be considered as a promising therapeutic target. However, whether KIFC1 is involved in the procession of renal cell carcinoma (RCC) still remains unclear. In this study, we found that KIFC1 was upregulated in RCC tissues and is responsible for RCC tumorigenesis (p < 0.001). The high expression of KIFC1 correlates with aggressive clinicopathologic parameters. Kaplan‐Meier analysis suggested that KIFC1 was associated with poor survival prognosis in RCC. Silencing KIFC1 dramatically resulted in inhibition of proliferation, delayed the cell cycle at G2/M phase, and suppressed cell invasion and migration in vitro. The antiproliferative effect of KIFC1 silencing was also observed in xenografted tumors in vivo. miR-338-3p could directly bind to the 3′-untranslated region (3′-UTR) of KIFC1, and ectopic miR-338-3p expression mimicked the inhibitory functions of KIFC1 silencing on RCC cells through inactivation of the PI3K/AKT signaling pathway. Therefore, these results revealed that KIFC1 may be a novel biomarker and an effective therapeutic target for the treatment of RCC.

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.

scholarly journals Effects of HMGA2 on the Epithelial-Mesenchymal Transition-Related Genes in ACHN Renal Cell Carcinoma Cells-Derived Xenografts in Nude Mice

2020 ◽  
Author(s):  
Guangyao Lv ◽  
Lingling Song ◽  
Guanyu Gong ◽  
Qian Chen ◽  
Kai Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Nude Mice ◽  
Renal Cell ◽  
Epithelial Mesenchymal Transition ◽  
Human Renal Cell Carcinoma ◽  
Mesenchymal Transition

Abstract Background: The architectural transcriptional regulator high-mobility group AT-hook 2 (HMGA2) is an oncofetal protein which has been reported to be ectopically expressed in a variety of cancers. A high expression of HMGA2 in human renal cell carcinoma (RCC) is related with tumor invasiveness and poor prognosis. In the in vitro studies, HMGA2 knockdown was found to lead to decreased cell proliferation, decreased migration and changes in gene expression related with the epithelial-mesenchymal transition. Methods: In order to understand HMGA2’s effect in vivo , HMGA2 expression was knocked-down in ACHN cells using small hairpin RNA (shRNA). The HMGA2-deficient ACHN cells were xenografted into the BALB/c nude mice. The tumor growth was monitored and the expression of EMT-related genes was analyzed. Results: HMGA2 expression was confirmed to be knocked-down in the cultured and xenografted ACHN cells. The xenograft tumor of HMGA2-deficient cells demonstrated a retarded growth pattern compared with control. The expression of E-cadherin was increased, whereas N-cadherin and Snail were decreased in the HMGA2-deficient xenograft tumors. Conclusions: The present study suggested that the epigenetic regulation of EMT-related gene expression by HMGA2 exists both in the in vitro and in vivo conditions. It is likely that through this mechanism, HMGA2 regulates the cell growth in renal cell carcinoma.

scholarly journals MEDAG enhances breast cancer progression and reduces epirubicin sensitivity through the AKT/AMPK/mTOR pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhiyu Li ◽  
Chenyuan Li ◽  
Qi Wu ◽  
Yi Tu ◽  
Changhua Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Clinicopathological Characteristics ◽  
Mtor Pathway ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

AbstractBreast cancer (BC) is the most common malignancy among women. Mesenteric estrogen-dependent adipogenesis gene (MEDAG) was first reported as a novel adipogenic gene, and its involvement and mechanism in visceral adiposity were analyzed. However, the role of MEDAG in BC is unclear. The biological roles and corresponding mechanisms were investigated in vitro and in vivo. We found that MEDAG was highly expressed in BC samples and that a high MEDAG expression was correlated with clinicopathological characteristics and poor survival in BC patients. MEDAG knockdown inhibited cell proliferation, invasion, and migration; triggered epithelial-to-mesenchymal transition (EMT); and enhanced epirubicin sensitivity in vitro. The opposite results were observed in MEDAG-overexpressing cells. The inhibition of MEDAG suppressed tumor growth and metastasis in vivo. Mechanistically, MEDAG knockdown led to decreased phosphorylation levels of AKT, increased levels of p-AMPK, and reduced levels of p-mTOR, while the overexpression of MEDAG had the opposite effects. Moreover, the activation of p-AKT and inhibition of p-AMPK restored the effect of MEDAG on EMT and chemosensitivity in BC cell lines, indicating that MEDAG functions as an oncogene by regulating the AKT/AMPK/mTOR pathway. MEDAG regulates BC progression and EMT via the AKT/AMPK/mTOR pathway and reduces chemosensitivity in BC cells. Therefore, MEDAG is a promising target for BC.

scholarly journals SNU-333 Cells as an Appropriate Cell Line for the Orthotopic Renal Cell Carcinoma Model

2021 ◽  
Vol 20 ◽  
pp. 153303382110384
Author(s):  
Inyoub Chang ◽  
Takbum Ohn ◽  
Daeun Moon ◽  
Young Hee Maeng ◽  
Bo Gun Jang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Renal Cell ◽  
Epithelial Mesenchymal Transition ◽  
Stem Cell Markers ◽  
Mesenchymal Transition ◽  
Cancer Stem Cell Markers

Objective: To investigate a feasible candidate for an appropriate cell line for the orthotopic renal cell carcinoma (RCC) model. Methods: Normal human proximal tubule cells (HK-2) and RCC cells were used for MTT assay, Western blotting, sphere-forming assay, and orthotopic injection of BALB/c-nude mice. Immunohistochemistry was adopted in tissue arrays and orthotopic tumors. Results: Primary RCC cells showed resistance to a GPX4 inhibitor compared to HK-2 and to metastatic RCC cells, Caki-1. Caki-2 and SNU-333 cells showed resistance to ferroptosis via increased GPX4 and FTH1, respectively. RCC cells showed increased αSMA, in which Caki-2 and SNU-333 cells exhibited different epithelial–mesenchymal transition and cancer stem cell markers. Caki-1 and SNU-333 cells formed spheres in vitro and orthotopic tumor masses in vivo. The injected SNU-333 tumor only showed high intensities of CD10 and PAX8, markers of renal origin. Conclusion: SNU-333 cell line exhibited resistance via iron metabolism and stemness, and had tumor-initiating capacities in vitro and in vivo. These results suggest that among the cells tested, SNU-333 cells were the most promising for the establishment of an orthotopic RCC model for further researches.

scholarly journals METTL13 Inhibits Progression of Clear Cell Renal Cell Carcinoma with Repression on PI3K/AKT/mTOR/HIF-1α Pathway and c-Myc Expression

2021 ◽  
Author(s):  
Zhuonan Liu ◽  
Tianshui Sun ◽  
Chiyuan Piao ◽  
Zhe Zhang ◽  
Chuize Kong
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cell Renal Cell Carcinoma ◽  
Mesenchymal Transition

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of renal malignancy. Methyltransferase like 13 (METTL13) functions as an oncogene in most of human cancers, but its function and mechanism in ccRCC remain unreported. Methods: qRT-PCR, western blot and immunohistochemistry were used to detect METTL13’s expressions in tissues. The effects of METTL13 on ccRCC cells’ growth and metastasis were determined by both functional experiments and animal experiments. Weighted gene co-expression network analysis (WGCNA) was performed to annotate METTL13’s functions and co-immunoprecipitation (co-IP) was used to determine the interaction between two proteins. Results: METTL13 was lowly expressed in ccRCC tissues compared to normal kidney tissues and its low expression predicted poor prognosis for ccRCC patients. In vitro study indicated METTL13’s inhibition on ccRCC cells’ proliferation, viability, migratory ability and invasiveness as well as epithelial-mesenchymal transition (EMT). Bioinformatic analyses showed various biological functions and pathways METTL13 was involved in. In ccRCC cells, we observed that METTL13 could negatively regulate PI3K/AKT/mTOR/HIF-1α pathway and that it combined to c-Myc and inhibited c-Myc expression. In vivo experiment confirmed that METTL13 inhibited ccRCC cell growth and metastasis. Conclusions: In general, our finding suggests that associated with favorable prognosis of ccRCC patients, METTL13 can inhibit growth and metastasis of ccRCC cells with multiple potential molecular mechanisms. Therefore, it’s likely for METTL13 to serve as a new diagnostic and therapeutic target for ccRCC in the future.

scholarly journals METTL13 inhibits progression of clear cell renal cell carcinoma with repression on PI3K/AKT/mTOR/HIF-1α pathway and c-Myc expression

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhuonan Liu ◽  
Tianshui Sun ◽  
Chiyuan Piao ◽  
Zhe Zhang ◽  
Chuize Kong
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cell Renal Cell Carcinoma ◽  
Mesenchymal Transition

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of renal malignancy. Methyltransferase like 13 (METTL13) functions as an oncogene in most of human cancers, but its function and mechanism in ccRCC remains unreported. Methods qRT-PCR, western blotting and immunohistochemistry were used to detect METTL13’s expression in tissues. The effects of METTL13 on ccRCC cells’ growth and metastasis were determined by both functional experiments and animal experiments. Weighted gene co-expression network analysis (WGCNA) was performed to annotate METTL13’s functions and co-immunoprecipitation (co-IP) was used to determine the interaction between METTL13 and c-Myc. Results METTL13 was underexpressed in ccRCC tissues compared to normal kidney tissues and its low expression predicted poor prognosis for ccRCC patients. The in vitro studies showed that knockdown and overexpression of METTL13 respectively led to increase and decrease in ccRCC cells’ proliferation, viability, migratory ability and invasiveness as well as epithelial-mesenchymal transition (EMT). The in vivo experiment demonstrated the inhibitory effect that METTL13 had on ccRCC cells’ growth and metastasis. Bioinformatic analyses showed various biological functions and pathways METTL13 was involved in. In ccRCC cells, we observed that METTL13 could negatively regulate PI3K/AKT/mTOR/HIF-1α pathway and that it combined to c-Myc and inhibited c-Myc protein expression. Conclusions In general, our finding suggests that high expression of METTL13 is associated with favorable prognosis of ccRCC patients. Meanwhile, METTL13 can inhibit growth and metastasis of ccRCC cells with participation in multiple potential molecular mechanisms. Therefore, we suggest METTL13 can be a new diagnostic and therapeutic target for ccRCC in the future.

scholarly journals Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Junjie Cen ◽  
Yanping Liang ◽  
Yong Huang ◽  
Yihui Pan ◽  
Guannan Shu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Expression Patterns ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Proliferation And Metastasis

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

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