Transcription factors NF-kB, HIF-1, HIF-2, growth factor VEGF, VEGFR2 and carboanhydrase IX mRNA and protein level in the development of kidney cancer metastasis

Спирина, Л. В.; Usynin, Y. A.; Yurmazov, Z. A.; Slonimskaya, Е. М.; Колегова, Е. С.; Kondakova, I. V.

doi:10.1134/s0026893317020194

Cited by 13 publications

(9 citation statements)

References 14 publications

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“…Previous studies have reported that VEGF, VEGFR2, and carbonic anhydrase IX regulated by HIF-1α are important biomarkers for ccRCC. 13,14 C-reactive protein (CRP) is known to participate in systemic inflammation in renal cell carcinoma, and its levels can be considered biomarkers for ccRCC. 15 Although some progress has been made in the search for biomarkers for renal tumors, most of which are based on clinical tissue or cellular levels, invasive surgery or puncture is inevitable.…”

Section: Discussionmentioning

confidence: 99%

“…Thus far, establishment of noninvasive biomarkers for the early diagnosis and follow‐up of renal cell carcinoma has received increasing attention and has been challenging. Previous studies have reported that VEGF, VEGFR2, and carbonic anhydrase IX regulated by HIF‐1α are important biomarkers for ccRCC . C‐reactive protein (CRP) is known to participate in systemic inflammation in renal cell carcinoma, and its levels can be considered biomarkers for ccRCC .…”

Section: Discussionmentioning

confidence: 99%

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Serum exosomal miR‐210 as a potential biomarker for clear cell renal cell carcinoma

Wang

Chen

et al. 2018

J of Cellular Biochemistry

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Exosomal microRNAs (miRNAs) are suggested to reflect molecular changes occurring in their cells of origin and are potential indicators in the early detection of cancers. This study aimed to determine whether certain exosomal miRNAs from tumor tissue can be used as noninvasive biomarkers for clear cell renal cell carcinoma (ccRCC). Based on ccRCC miRNA expression profiles and the literature, we selected six miRNAs (miR‐210, miR‐224, miR‐452, miR‐155, miR‐21, and miR‐34a) and analyzed their expression in tissues, sera, and serum exosomes through quantitative real‐time polymerase chain reaction in hypoxia‐induced (with CoCl2) renal cell lines. miR‐210, miR‐224, miR‐452, miR‐155, and miR‐21 were upregulated in tumor tissues compared with normal tissues. Serum miR‐210 and miR‐155 levels were higher in patients with ccRCC than in healthy controls (HCs). Furthermore, only exosomal miR‐210 was significantly upregulated in patients with ccRCC than in HCs. Moreover, receiver operating characteristic (ROC) curve analysis revealed an area under the ROC curve of 0.8779 (95% confidence interval, 0.7987‐0.9571) and a sensitivity and specificity of 82.5% and 80.0%, respectively. Moreover, exosomal miR‐210 was upregulated at an advanced stage, and Fuhrman grade and metastasis decreased significantly one month after surgery. Acute hypoxia exposure activates miR‐210 and release of exosomes with upregulated miR‐210 in both normal and tumor RCC cell lines and interferes with vacuole membrane protein 1 mRNA expression, especially in the metastatic ccRCC cell line. In conclusion, Serum exosomal miR‐210 originating from tumor tissue has potential as a novel noninvasive biomarker for the detection and prognosis of ccRCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serum exosomal miR‐210 as a potential biomarker for clear cell renal cell carcinoma

Wang

Chen

et al. 2018

J of Cellular Biochemistry

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“…Notch pathway controls the activation of NF-κB pathway by activating CSL protein in the side effector cells 31. An important downstream target gene of NF-κB pathway is VEGF, which is closely related to the invasion and metastasis of cervical cancer32. In this study, our observation proved that curcumin-PDT can block Notch signaling pathway and tune down the expression of key factors such as Notch-1 and NF-κB, thus inhibiting tumor growth.…”

Section: Discussionmentioning

confidence: 55%

Effects of Notch Signaling Pathway in Cervical Cancer by Curcumin Mediated Photodynamic Therapy and Its Possible Mechanisms in Vitro and in Vivo

He¹,

Mu²,

Yuan³

et al. 2019

J. Cancer

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Curcumin, as a high effect and low toxicity anti-cancer drug and photosensitiser, has synergistic and complementary effects with photodynamic therapy (PDT). However, due to its unclear mechanism, PDT's application and efficacy were limited. Notch signaling pathway, which is highly correlates with carcinogenesis and development of cervical cancer, could be a potential therapeutic targets to improve the effectiveness of PDT. Therefore, in this study, we explored the effects of Notch signaling pathway in cervical cancer by curcumin mediated PDT with/without Notch receptor blocker (DAPT), and hope to elucidate its mechanism. Firstly, the effect on the proliferation of cervical cancer Me180 cells were detected with MTT assay, and apoptosis were detected with Annexin V-FITC/PI combined with flow cytometry. Secondly, after establishment of nude mice model, dividing the experimental animals into model group, curcumin PDT group, simple DAPT group, and curcumin-PDT+DAPT group, and analyzing tumor volume changes as well as HE staining in each group. mRNA and protein expression of gene Notch-1 and its downstream NF-κB and VEGF were observed with RT-PCR, immunohistochemical staining and Western-blot with/without inhibition of Notch signaling pathway by DAPT, both in vivo and in vitro experiments. We found both DAPT and curcumin-PDT can inhibit the proliferation and induce apoptosis of cervical cancer cell. The two have synergistic effect in vitro and in vivo. This effect can effectively block the conduction of Notch signaling pathway, which is associated with down-regulation of the expression of Notch1 and NF-κB. Notch signaling pathway could be one of the targets of curcumin-PDT photodynamic therapy.

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“…PTEN deficiency contributes to the development and progression of ccRCC. Shorter overall survival in ccRCC patients is correlated with low PTEN expression [12,24].…”

Section: Discussionmentioning

confidence: 99%

Molecular Protein and Expression Profile in the Primary Tumors of Clear Cell Renal Carcinoma and Metastases

Спирина

Yurmazov

Gorbunov

et al. 2020

Cells

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Metastasis involves the spread of cancer cells from the primary tumor to surrounding tissues and distant organs and is the primary cause of cancer morbidity and mortality. The aim of the study was the determination of change in molecular factors expression in primary kidney cancers (ccRCC) and metastatic sites. In total, 62 patients with RCC were enrolled in the study. The mRNA levels of molecular markers were studied by real-time PCR, and the content of the studied parameters was determined by Western blotting and ELISA. The features in the intracellular signal metabolites in the series of normal renal parenchyma, tumor tissue of localized, disseminated kidney cancer and metastatic tissue were studied. A decrease in some indicators in the tissue of the metastatic lesion was noted. Protein products of transcription factors HIF-1, CAIX, PTEN and activated AKT kinase, as well as expression of the VEGFR2 receptor and m-TOR protein kinase were revealed to be reduced in the metastatic sites. In addition, some indicators increased in metastasis: the protein levels of NF-κB p 50, NF-κB p 65, HIF-2, VEGF, VEGFR2, m-TOR and mRNA of HIF-1, CAIX, PTEN and PDK. There were indicators with multidirectional changes. HIF-1, CAIX, PTEN, VEGFR2 and m-TOR mRNA: VEGFR2, m-TOR, HIF-1, CAIX, PTEN and PDK had an opposite change in protein content and mRNA level. PTEN loss resulted in the downstream activation of AKT/mTOR signaling in secondary cancer lesions and determined the overall ccRCC patient’s survival. The AKT/mTOR signaling cascade activation was found in the primary kidney tumors. The PTEN content and mRNA level were correlated with total AKT, GSK-3β, the 70S 6 kinases and AKT expression.

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Transcription factors NF-kB, HIF-1, HIF-2, growth factor VEGF, VEGFR2 and carboanhydrase IX mRNA and protein level in the development of kidney cancer metastasis

Cited by 13 publications

References 14 publications

Serum exosomal miR‐210 as a potential biomarker for clear cell renal cell carcinoma

Serum exosomal miR‐210 as a potential biomarker for clear cell renal cell carcinoma

Effects of Notch Signaling Pathway in Cervical Cancer by Curcumin Mediated Photodynamic Therapy and Its Possible Mechanisms in Vitro and in Vivo

Molecular Protein and Expression Profile in the Primary Tumors of Clear Cell Renal Carcinoma and Metastases

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