HNF‑4α downregulation promotes tumor migration and invasion by regulating E‑cadherin in renal cell carcinoma

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.

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Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis

Cellular Physiology and Biochemistry ◽

10.1159/000489658 ◽

2018 ◽

Vol 46 (6) ◽

pp. 2517-2531 ◽

Cited By ~ 6

Author(s):

Xiaobing Liu ◽

Dangling Zhang ◽

Yaxing Hao ◽

Qian Liu ◽

Yuqi Wu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Western Blot ◽

Cell Carcinoma ◽

Renal Cell ◽

The Cancer Genome Atlas ◽

Cell Counting ◽

Migration And Invasion ◽

Rna Seq ◽

Rt Pcr ◽

E Cadherin

Background/Aims: Cyanidin is an anthocyanin found in many foods. Although its variable antioxidant levels are well-documented, little is known about its effects on renal cell carcinoma (RCC) tumorigenesis. This study, therefore, investigated the effects of cyanidin on the proliferation, migration, and invasion of renal cell carcinoma lines and demonstrated, for the first time, significant inhibitory effects of cyanidin on RCC tumorigenesis. Methods: RCC cells were treated with different doses of cyanidin and the effects were tested by Cell Counting Kit-8 reagent, clone formation assay, transwell assay, and flow cytometry. Moreover, the cyanidin-mediated mechanism that curtailed tumorigenesis was analyzed by RNA sequencing (RNA-seq). Sequencing data from The Cancer Genome Atlas (TCGA) were used to compare the expression of both early growth response protein 1 (EGR1) and selenoprotein W (SEPW1) in RCC and tumor-free adjacent normal tissue samples. Real-time PCR (RT-PCR) and/or western blot were used to assess the expression of E-cadherin, cleaved-caspase3, Bcl2, p62, and ATG4. Results: We found significantly greater induction of cell-cycle arrest, apoptosis, and suppression of RCC cell invasion and migration at concentrations of 25 µM and 100 µM than at a concentration of 50 µM. It was also discovered, first through RNA-seq then confirmed by RT-PCR, that cyanidin (100 µM) inhibited RCC carcinogenesis through EGR1 and SEPW1. TCGA data indicated that the expression level of EGR1 was lower and that of SEPW1 was higher in RCC tumor tissue than in normal tissues. Moreover, western blot and/or RT-PCR indicated that cleaved-caspase3 was enhanced and E-cadherin was inhibited by cyanidin treatment. Furthermore, western blot and RT-PCR also showed regulation of p62 and ATG4, which are associated with autophagy. Cyanidin in vivo significantly inhibited the growth of xenografts in nude mice. Conclusions: The results of this study showed the therapeutic potential of cyanidin for the treatment of RCC and the prevention of recurrence and metastasis.

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Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals

Molecular Cancer ◽

10.1186/s12943-019-1072-5 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 29

Author(s):

Dingwei Xue ◽

Huan Wang ◽

Yuanlei Chen ◽

Danyang Shen ◽

Jieyang Lu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Cell Renal Cell Carcinoma ◽

E Cadherin

Abstract Background Circular RNA (circRNA) is a type of circular endogenous RNA produced by special selective splicing and participates in progression of diverse diseases. However, the role of circRNA in clear cell renal cell carcinoma (ccRCC) is still rarely reported. Methods We detected lower circ-AKT3 expression in ccRCC using the circular RNA microarray. Then, qPCR array was applied to verify the expression of circ-AKT3 in between 60 ccRCC tissues and adjacent normal tissues, as well as ccRCC cell lines and human normal kidney cell (HK-2). We investigated the function of circ-AKT3 in ccRCC in vitro and in vivo and detected underlying mechanisms by Western blotting, bioinformatic analysis, RNA pull-down assay and luciferase reporter assay. Results Circ-AKT3 was verified significantly downregulated in ccRCC. Knockdown of circ-AKT3 promoted ccRCC migration and invasion, while overexpression of circ-AKT3 suppressed ccRCC metastasis. Further, circ-AKT3/miR-296-3p/E-cadherin axis was shown responsible for circ-AKT3 inhibiting ccRCC metastasis. Conclusion Circ-AKT3 suppresses ccRCC metastasis by enforcing E-cadherin expression through competitively binding miR-296-3p. Circ-AKT3 may therefore serve as a novel therapeutic to better suppress ccRCC metastasis.

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Enhancer of zeste homolog 2 (EZH2) promotes tumour cell migration and invasion via epigenetic repression of E-cadherin in renal cell carcinoma

BJU International ◽

10.1111/bju.12702 ◽

2015 ◽

Vol 117 (2) ◽

pp. 351-362 ◽

Cited By ~ 51

Author(s):

Li Liu ◽

Zhibing Xu ◽

Lei Zhong ◽

Hang Wang ◽

Shuai Jiang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Migration ◽

Cell Carcinoma ◽

Tumour Cell ◽

Renal Cell ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Enhancer Of Zeste ◽

Epigenetic Repression ◽

E Cadherin

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Positive feedback regulation of lncRNA PVT1 and HIF2α contributes to clear cell renal cell carcinoma tumorigenesis and metastasis

Oncogene ◽

10.1038/s41388-021-01971-7 ◽

2021 ◽

Author(s):

Ming-xiao Zhang ◽

Li-zhen Zhang ◽

Liang-min Fu ◽

Hao-hua Yao ◽

Lei Tan ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Positive Feedback ◽

Renal Cell ◽

Clear Cell ◽

Biological Significance ◽

Specific Inhibitor ◽

Migration And Invasion ◽

Loss Of Function ◽

Cell Renal Cell Carcinoma

AbstractLong noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.

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Re: Tumour-Suppressive MicroRNA-29s Directly Regulate LOXL2 Expression and Inhibit Cancer Cell Migration and Invasion in Renal Cell Carcinoma

The Journal of Urology ◽

10.1016/j.juro.2016.02.003 ◽

2016 ◽

Vol 195 (5) ◽

pp. 1622-1622

Author(s):

Anthony Atala

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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Resveratrol inhibits proliferation, migration and invasion via Akt and ERK1/2 signaling pathways in renal cell carcinoma cells

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2017.12.029 ◽

2018 ◽

Vol 98 ◽

pp. 36-44 ◽

Cited By ~ 22

Author(s):

Yuwan Zhao ◽

Huancheng Tang ◽

Xin Zeng ◽

Dongcai Ye ◽

Jianjun Liu

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathways ◽

Renal Cell ◽

Carcinoma Cells ◽

Migration And Invasion

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CpG methylation of promoter region inactivates E-cadherin gene in renal cell carcinoma

Molecular Carcinogenesis ◽

10.1002/mc.1060 ◽

2001 ◽

Vol 32 (1) ◽

pp. 19-27 ◽

Cited By ~ 44

Author(s):

Dana Nojima ◽

Koichi Nakajima ◽

Long-Cheng Li ◽

Joseph Franks ◽

Leopoldo Ribeiro-Filho ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Promoter Region ◽

Cpg Methylation ◽

E Cadherin

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IgG is involved in the migration and invasion of clear cell renal cell carcinoma

Journal of Clinical Pathology ◽

10.1136/jclinpath-2015-202881 ◽

2015 ◽

Vol 69 (6) ◽

pp. 497-504 ◽

Cited By ~ 7

Author(s):

Zhengzuo Sheng ◽

Yang Liu ◽

Caipeng Qin ◽

Zhenhua Liu ◽

Yeqing Yuan ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Western Blot ◽

Cell Carcinoma ◽

Cell Lines ◽

Renal Cell ◽

Clear Cell ◽

Migration And Invasion ◽

Cancer Therapies ◽

Normal Kidney ◽

Cell Renal Cell Carcinoma

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

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