The Gut Microbiota Activates AhR Through the Tryptophan Metabolite Kyn to Mediate Renal Cell Carcinoma Metastasis

Background: The incidence of renal cell carcinoma (RCC) is increasing year by year. It is difficult to have complete treatment so far. Studies have shown that tryptophan metabolite Kynurenine (Kyn) affects cell proliferation, migration, apoptosis, adhesion, and differentiation. Our aim is to explore whether Kyn activates aromatic hydrocarbon receptor (AhR) to mediate RCC metastasis.Methods: We collected RCC tissues and feces from RCC patients. 16S rRNA technology was performed to analyze the gut microbial composition of RCC patients. LC-MS/MS was used to analyze the gut microbial metabolites. The AhR was inhibited and treated with Kyn. Immunofluorescence was used to measure the degree of AhR activation. The migration and invasion ability of 786-O cells was tested by Transwell assay. Flow cytometry and cell cycle assay were utilized to observe the apoptosis and cycle of 786-O cells. CCK-8 assay was used to detect 786-O cells proliferation. qRT-PCR and Western blot were used to detect AhR and EMT-related genes expression level.Results: AhR expression was up-regulated in RCC tissues. RCC gut microbiota was disordered. The proportion of Kyn was increased in RCC. After being treated with Kyn, the migration, invasion, and proliferation ability of 786-O cells were decreased. Furthermore, the expression of EMT-related protein E-cadherin decreased, and the expression of N-cadherin and Vimentin increased. The proportion of 786-O cells in the S phase increased. The apoptosis rate of 786-O cells was inhibited.Conclusion: The tryptophan metabolite Kyn could activate AhR. Kyn could promote 786-O cells migration and invasion. Gut microbiota could activate AhR through its tryptophan metabolite Kyn to mediate RCC metastasis.

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PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression

Cell Death Discovery ◽

10.1038/s41420-021-00725-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Lifeng Ding ◽

Ruyue Wang ◽

Wanjiang Xu ◽

Danyang Shen ◽

Sheng Cheng ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Migration And Invasion ◽

Erk Pathway ◽

Cell Renal Cell Carcinoma ◽

Metastasis Model ◽

Renal Cell Carcinoma Metastasis

AbstractClear-cell renal cell carcinoma is one of the most common tumors disagnosed, with nearly one third of patients diagnosed with metastatic ccRCC. Although an increasing number of studies has revealed that piwi-interacting RNAs are aberrantly expressed in diverse types of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particularly in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC were selected by using piRNA-sequencing combined with TCGA data analysis, and piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could potentially reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further study revealed that piR-57125 modulated ccRCC metastasis through the AKT/ERK pathway. These data indicate that piR-57125 restrains ccRCC metastasis by directly targeting CCL3 and inhibiting the AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.

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Renal cell carcinoma metastasis to thyroid tumor: a case report

Endocrine Abstracts ◽

10.1530/endoabs.49.gp239 ◽

2017 ◽

Author(s):

Carolina Faria ◽

David Barbosa ◽

Ana Sofia Osorio ◽

Ema Nobre ◽

Maria Joao Bugalho

Keyword(s):

Renal Cell Carcinoma ◽

Case Report ◽

Cell Carcinoma ◽

Renal Cell ◽

Thyroid Tumor ◽

Renal Cell Carcinoma Metastasis ◽

Carcinoma Metastasis

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Significant association of interleukin 10 receptor mRNA levels with renal cell carcinoma metastasis

Biomedical Research ◽

10.2220/biomedres.29.19 ◽

2008 ◽

Vol 29 (1) ◽

pp. 19-25 ◽

Cited By ~ 5

Author(s):

Hideyuki ABE ◽

Tomonori YAMANISHI ◽

Tomoko MASHIDORI ◽

Kyoko ARAI ◽

Takao KAMAI

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Interleukin 10 ◽

Mrna Levels ◽

Receptor Mrna ◽

Renal Cell Carcinoma Metastasis ◽

Carcinoma Metastasis

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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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Renal cell carcinoma metastasis to the parathyroid gland: A very rare occurrence

International Journal of Surgery Case Reports ◽

10.1016/j.ijscr.2014.04.010 ◽

2014 ◽

Vol 5 (7) ◽

pp. 378-380 ◽

Cited By ~ 4

Author(s):

Enyinnaya Ofo ◽

Rishi Mandavia ◽

Jean-Pierre Jeannon ◽

Edward Odell ◽

Ricard Simo

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Parathyroid Gland ◽

Renal Cell ◽

Rare Occurrence ◽

Renal Cell Carcinoma Metastasis ◽

Carcinoma Metastasis

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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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