scholarly journals Overexpression of SOX4 promotes cell migration and invasion of renal cell carcinoma by inducing epithelial-mesenchymal transition

2017 ◽  
Vol 51 (1) ◽  
pp. 336-346 ◽  
Author(s):  
Hailong Ruan ◽  
Hongmei Yang ◽  
Haibin Wei ◽  
Wen Xiao ◽  
Ning Lou ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

scholarly journals Elevated MTA1 induced the migration and invasion of renal cell carcinoma through the NF-κB pathway

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Cai Lv ◽  
Yuan Huang ◽  
Qingqing Lei ◽  
Zhenxiang Liu ◽  
Shixing Shen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Normal Tissue ◽  
Negative Control ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Interfering Rna ◽  
E Cadherin

Abstract Background The metastasis-associated gene 1 (MTA1) has been extensively reported as a crucial oncogene, and its abnormal expression has been associated with the progression of numerous cancers. However, the role of MTA1 in renal cell carcinoma (RCC) progression and metastasis remains unclear. Herein, we investigated the expression of MTA1 and its role in RCC. Methods 109 matched clear cell RCCs (ccRCCs) and corresponding normal tissue samples were analyzed via immunohistochemistry to test the expression of MTA1. Human A498 cell lines were transfected with pcDNA3.1-Flag (control) or Flag-MTA1 to overexpress MTA1 or with specific interfering RNA (si-MTA1) or specific interfering negative control to knockdown MTA1 expression. Transfected cells were used in wound healing and transwell invasion assay. Quantitative real time polymerase chain reaction was used to assess the effect of MTA1 on MMP2/MMP9 and E-cadherin gene expression. Western blot was used to qualify the phosphorylation of p65. Results Herein, we found a significantly increased expression of MTA1 in 109 ccRCCs, compared to the corresponding normal tissue. In addition, the overexpression of MTA1 in A498 cells facilitated cell migration and invasion, while the down-regulation of MTA1 expression using specific interfering RNA sequences could decrease cell migration and invasion. Furthermore, we showed that MTA1 is up-regulated in ccRCCs, which contributes to the migration and invasion of human kidney cancer cells by mediating the expression of MMP2 and MMP9 through the NF-κB signaling pathway. Similarly, we found that MTA1 could regulate E-cadherin expression in RCCs. Conclusions MTA1 is overexpressed in RCC and is involved in the progression of RCC through NF-κB.

scholarly journals Upregulated circPDK1 Promotes RCC Cell Migration and Invasion by Regulating the miR-377-3P-NOTCH1 Axis in Renal Cell Carcinoma

2020 ◽  
Vol Volume 13 ◽  
pp. 11237-11252
Author(s):  
Zhenlin Huang ◽  
Yinghui Ding ◽  
Lu Zhang ◽  
Siyuan He ◽  
Zhankui Jia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

scholarly journals Regulation of Oncogenic Targets by the Tumor-Suppressive miR-139 Duplex (miR-139-5p and miR-139-3p) in Renal Cell Carcinoma

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 599
Author(s):  
Reona Okada ◽  
Yusuke Goto ◽  
Yasutaka Yamada ◽  
Mayuko Kato ◽  
Shunichi Asai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Molecular Pathogenesis ◽  
Molecular Networks ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Passenger Strand

We previously found that both the guide and passenger strands of the miR-139 duplex (miR-139-5p and miR-139-3p, respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of miR-139-5p (p < 0.0001) and miR-139-3p (p < 0.0001) was closely associated with 5-year survival rates of patients with renal cell carcinoma (RCC). Ectopic expression assays showed that miR-139-5p and miR-139-3p acted as tumor-suppressive miRNAs in RCC cells. Here, 19 and 22 genes were identified as putative targets of miR-139-5p and miR-139-3p in RCC cells, respectively. Among these genes, high expression of PLXDC1, TET3, PXN, ARHGEF19, ELK1, DCBLD1, IKBKB, and CSF1 significantly predicted shorter survival in RCC patients according to TCGA analyses (p < 0.05). Importantly, the expression levels of four of these genes, PXN, ARHGEF19, ELK1, and IKBKB, were independent prognostic factors for patient survival (p < 0.05). We focused on PXN (paxillin) and investigated its potential oncogenic role in RCC cells. PXN knockdown significantly inhibited cancer cell migration and invasion, possibly by regulating epithelial–mesenchymal transition. Involvement of the miR-139-3p passenger strand in RCC molecular pathogenesis is a new concept. Analyses of tumor-suppressive-miRNA-mediated molecular networks provide important insights into the molecular pathogenesis of RCC.

scholarly journals The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Solange Rivas ◽  
Patricio Silva ◽  
Montserrat Reyes ◽  
Hugo Sepúlveda ◽  
Luis Solano ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Proximal Promoter ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tumor Cell Migration ◽  
Rab Protein

AbstractTumor hypoxia and the hypoxia inducible factor-1, HIF-1, play critical roles in cancer progression and metastasis. We previously showed that hypoxia activates the endosomal GTPase Rab5, leading to tumor cell migration and invasion, and that these events do not involve changes in Rab protein expression, suggesting the participation of intermediate activators. Here, we identified ALS2, a guanine nucleotide exchange factor that is upregulated in cancer, as responsible for increased Rab5-GTP loading, cell migration and metastasis in hypoxia. Specifically, hypoxia augmented ALS2 mRNA and protein levels, and these events involved HIF-1α-dependent transcription, as shown by RNAi, pharmacological inhibition, chromatin immunoprecipitation and bioinformatics analyses, which identified a functional HIF-1α-binding site in the proximal promoter region of ALS2. Moreover, ALS2 and Rab5 activity were elevated both in a model of endogenous HIF-1α stabilization (renal cell carcinoma) and by following expression of stable non-hydroxylatable HIF-1α. Strikingly, ALS2 upregulation in hypoxia was required for Rab5 activation, tumor cell migration and invasion, as well as experimental metastasis in C57BL/6 mice. Finally, immunohistochemical analyses in patient biopsies with renal cell carcinoma showed that elevated HIF-1α correlates with increased ALS2 expression. Hence, this study identifies ALS2 as a novel hypoxia-inducible gene associated with tumor progression and metastasis.

scholarly journals Tumor suppressive microRNA-138 contributes to cell migration and invasion through its targeting of vimentin in renal cell carcinoma

2012 ◽  
Vol 41 (3) ◽  
pp. 805-817 ◽  
Author(s):  
TAKESHI YAMASAKI ◽  
NAOHIKO SEKI ◽  
YASUTOSHI YAMADA ◽  
HIROFUMI YOSHINO ◽  
HIDEO HIDAKA ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

scholarly journals MicroRNA-138 suppresses epithelial–mesenchymal transition in squamous cell carcinoma cell lines

2011 ◽  
Vol 440 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Xiqiang Liu ◽  
Cheng Wang ◽  
Zujian Chen ◽  
Yi Jin ◽  
Yun Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Direct Targeting

Down-regulation of miR-138 (microRNA-138) has been frequently observed in various cancers, including HNSCC (head and neck squamous cell carcinoma). Our previous studies suggest that down-regulation of miR-138 is associated with mesenchymal-like cell morphology and enhanced cell migration and invasion. In the present study, we demonstrated that these miR-138-induced changes were accompanied by marked reduction in E-cad (E-cadherin) expression and enhanced Vim (vimentin) expression, characteristics of EMT (epithelial–mesenchymal transition). On the basis of a combined experimental and bioinformatics analysis, we identified a number of miR-138 target genes that are associated with EMT, including VIM, ZEB2 (zinc finger E-box-binding homeobox 2) and EZH2 (enhancer of zeste homologue 2). Direct targeting of miR-138 to specific sequences located in the mRNAs of the VIM, ZEB2 and EZH2 genes was confirmed using luciferase reporter gene assays. Our functional analyses (knock-in and knock-down) demonstrated that miR-138 regulates the EMT via three distinct pathways: (i) direct targeting of VIM mRNA and controlling the expression of VIM at a post-transcriptional level, (ii) targeting the transcriptional repressors (ZEB2) which in turn regulating the transcription activity of the E-cad gene, and (iii) targeting the epigenetic regulator EZH2 which in turn modulates its gene silencing effects on the downstream genes including E-cad. These results, together with our previously observed miR-138 effects on cell migration and invasion through targeting RhoC (Rho-related GTP-binding protein C) and ROCK2 (Rho-associated, coiled-coil-containing protein kinase 2) concurrently, suggest that miR-138 is a multi-functional molecular regulator and plays major roles in EMT and in HNSCC progression.

scholarly journals Tumour-suppressivemicroRNA-29sdirectly regulateLOXL2expression and inhibit cancer cell migration and invasion in renal cell carcinoma

FEBS Letters ◽  
2015 ◽  
Vol 589 (16) ◽  
pp. 2136-2145 ◽  
Author(s):  
Rika Nishikawa ◽  
Takeshi Chiyomaru ◽  
Hideki Enokida ◽  
Satoru Inoguchi ◽  
Tomoaki Ishihara ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Cancer Cell ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion
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