VHL, BAP1, PBRM1, SETD2 Expression in Clear Cell Renal Carcinoma, Association With PD-1, PD-L1, PD-L2 mRNA Level

Novel mechanism of ccRCC progression is essential, including PBRM1, BAP1, and SETD2 in histone-modifying and chromatin remodeling genes. The study aimed to investigate VHL, PD-1, PD-L1, PD-L2. BAP1, PBRM1, SETD2 expression in ccRCC primary cancers and metastatic tissues associated with the cancer dissemination. A total of 62 patients with RCC were enrolled in the study. Investigation of mRNA level of VHL, PD-1, PD-L1, PD-L2. PCR in real-time performed BAP1, PBRM1, SETD2 with the previous RNA isolation. Western Blotting analysis was used for detecting the p-VHL protein content in tissues. The VHL expression and p-VHL content determined the aggressive cancer behavior and elevated in disseminated tumors. The cancer dissemination was accompanied by an increase in both mRNA and VHL content. The PD-L2 prevalence in metastatic cancers is crucial in tumor progression. ccRCC progression in VHL overexpression is associated with the decrease in BAP1 gene expression. It is revealed the heterogeneity in molecular markers in primary tumors and metastases. The low mRNA level of BAP1, PBRM1, SETD2, PD-1, PD-L1, PD-L2 in metastases compared with primary tumors were found. We show a novel mechanism for VHL tumor progression and present a new instrument and factor targeting tumor-related pathologies with p-VHL/HIF altered function.

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Regulation of Immunity in Clear Cell Renal Carcinoma: Role of PD-1, PD-L1, and PD-L2

Current Issues in Molecular Biology ◽

10.3390/cimb43020076 ◽

2021 ◽

Vol 43 (2) ◽

pp. 1072-1080

Author(s):

Liudmila Spirina ◽

Zahar Yurmazov ◽

Evgeny Usynin ◽

Irina Kondakova ◽

Ekaterine Ladutko ◽

...

Keyword(s):

Growth Factors ◽

Cancer Progression ◽

Clear Cell ◽

Mrna Level ◽

Aggressive Cancer ◽

New Instrument ◽

Cell Renal Carcinoma ◽

Vhl Protein ◽

Cancer Dissemination ◽

Mtor Modulation

Regulation of immunity is a unique oncogenic mechanism that differs in different cancers. VHL deficient clear cell renal cell carcinomas (ccRCC) trigger the immune response resulting in cancer progression. This study aimed to investigate PD-1, PD-L1, and PD-L2 expression in ccRCC primary cancers and metastatic tissues associated with the p-VHL content, transcriptional, and growth factors expression. Methods: A total of 62 patients with RCC were enrolled in the study. Investigation of mRNA level was performed by PCR in real-time. Western blotting analysis was used for detecting the p-VHL protein content in tissues. Results: The PD-L2 prevalence in metastatic cancers is crucial in tumor progression. The VHL expression and p-VHL content determined the aggressive cancer behavior and elevated in disseminated tumors. The cancer dissemination was accompanied by an increase in both mRNA and VHL content. Conclusion: We present a new instrument targeting pathologies with p-VHL/HIF altered function that impact the PD-L2 expression through the change in transcriptional, growth factors, and AKT/mTOR modulation.

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Conventional (clear cell) renal carcinoma metastases have greater bcl-2 expression than high-risk primary tumors

Urologic Oncology Seminars and Original Investigations ◽

10.1016/s1078-1439(02)00236-3 ◽

2003 ◽

Vol 21 (3) ◽

pp. 179-184 ◽

Cited By ~ 24

Author(s):

Cheryl T. Lee ◽

Elizabeth M. Genega ◽

Brian Hutchinson ◽

Paul A. Fearn ◽

Michael W. Kattan ◽

...

Keyword(s):

High Risk ◽

Renal Carcinoma ◽

Clear Cell ◽

Clear Cell Renal Carcinoma ◽

Primary Tumors ◽

Cell Renal Carcinoma

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GYS1 induces glycogen accumulation and promotes tumor progression via the NF-κB pathway in Clear Cell Renal Carcinoma

Theranostics ◽

10.7150/thno.46825 ◽

2020 ◽

Vol 10 (20) ◽

pp. 9186-9199

Author(s):

Shi-lu Chen ◽

Qun-sheng Huang ◽

Yu-hua Huang ◽

Xia Yang ◽

Ming-ming Yang ◽

...

Keyword(s):

Tumor Progression ◽

Renal Carcinoma ◽

Clear Cell ◽

Clear Cell Renal Carcinoma ◽

Glycogen Accumulation ◽

Cell Renal Carcinoma

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1651: Molecular Prognostic Modeling Using Protein Expression Profile in Clear Cell Renal Carcinoma

The Journal of Urology ◽

10.1016/s0022-5347(18)38859-1 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 436-436 ◽

Cited By ~ 3

Author(s):

Hyung L. Kim ◽

David B. Seligson ◽

Nicolette Janzen ◽

Matthew H. Bui ◽

Robert A. Figlin ◽

...

Keyword(s):

Protein Expression ◽

Expression Profile ◽

Renal Carcinoma ◽

Clear Cell ◽

Clear Cell Renal Carcinoma ◽

Protein Expression Profile ◽

Cell Renal Carcinoma ◽

Prognostic Modeling

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Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer

Cancers ◽

10.3390/cancers13081839 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1839

Author(s):

Karolina Seborova ◽

Radka Vaclavikova ◽

Lukas Rob ◽

Pavel Soucek ◽

Pavel Vodicka

Keyword(s):

Ovarian Cancer ◽

Tumor Progression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Distant Metastases ◽

Regulatory Elements ◽

Metastatic Spread ◽

Response To Treatment ◽

Primary Tumors ◽

Non Coding Rnas

Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.

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The VHL tumor suppressor inhibits expression of the IGF1R and its loss induces IGF1R upregulation in human clear cell renal carcinoma

Oncogene ◽

10.1038/sj.onc.1210474 ◽

2007 ◽

Vol 26 (45) ◽

pp. 6499-6508 ◽

Cited By ~ 68

Author(s):

J S P Yuen ◽

M E Cockman ◽

M Sullivan ◽

A Protheroe ◽

G D H Turner ◽

...

Keyword(s):

Tumor Suppressor ◽

Renal Carcinoma ◽

Clear Cell ◽

Clear Cell Renal Carcinoma ◽

Cell Renal Carcinoma

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The Influence of the Extremely Low Frequency Electromagnetic Field on Clear Cell Renal Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms22031342 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1342

Author(s):

Aleksandra Cios ◽

Martyna Ciepielak ◽

Wanda Stankiewicz ◽

Łukasz Szymański

Keyword(s):

Electromagnetic Field ◽

Cancer Cells ◽

Cell Lines ◽

Renal Carcinoma ◽

Clear Cell ◽

Low Frequency ◽

Inhibitory Effect ◽

Hek293 Cells ◽

Clear Cell Renal Carcinoma ◽

Cell Renal Carcinoma

The development of new technologies and industry is conducive to the increase in the number and variety of electromagnetic field (EMF) sources in our environment. The main sources of EMF are high-voltage lines, household appliances, audio/video devices, mobile phones, radio stations, and radar devices. In the growing use of electronic devices, scientists are increasingly interested in the effects of EMF on human health. Even though many studies on the effects of EMF have already been carried out, none of them has shown a significant effect on mammals, including humans. Moreover, it is not entirely clear how EMF influences cell behavior. The International Agency for Research on Cancer on 31 May 2011, classified PEM as a possible carcinogenic factor. This study aimed to investigate the effect of the electromagnetic field on morphological and functional changes in clear cell renal carcinoma. The research was carried out on in vitro cultures of four cell lines: HEK293, 786-O 769-P, and Caki1. The results of the research showed that the EMF of low frequency had a slight effect on the viability of cells. EMF, which induced cell arrest in the G1 phase, increased the number of early apoptotic cells and decreased the number of viable cells in the 786-O line. EMF did not affect the proliferation and viability of HEK293 cells. Extreme low-frequency EMF (ELF-EMF) also showed an inhibitory effect on the migration and metastatic properties of clear cell kidney cancer cells. Moreover, shortly after the end of ELF-EMF exposure, significant increases in ROS levels were observed in all tested cell lines. As part of the work, it was shown that low-frequency EMF shows an inhibitory effect on the proliferation of primary cancer cells, diminishing their migratory, invasive, and metastatic abilities. It also increases the apoptosis of cancer cells and the amount of reactive oxygen species. Based on the results of our research, we want to point up that the effect of ELF-EMF depends on a specific metabolic state or at a specific stage in the cell cycle of the cells under study.

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