Bartlomiej E Krazinski1, Jolanta Kiewisz2, Agnieszka Sliwinska-Jewsiewicka2, Anna E Kowalczyk2, Jedrzej Grzegrzolka3, Janusz Godlewski2, Przemyslaw Kwiatkowski2, Piotr Dziegiel3,4, Zbigniew Kmiec2,5. 1. Department of Human Histology and Embryology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland bartlomiej.krazinski@uwm.edu.pl. 2. Department of Human Histology and Embryology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland. 3. Department of Human Morphology and Embryology, Division of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland. 4. Department of Physiotherapy, Wroclaw University School of Physical Education, Wroclaw, Poland. 5. Department of Histology, Medical University of Gdansk, Gdansk, Poland.
Abstract
BACKGROUND/AIM: Accumulating evidence suggests that discoidin domain receptor tyrosine kinase 1 (DDR1) has an oncogenic role. Therefore, the aim of this study was to evaluate the potential utility of DDR1 and its post-transcriptional repressors, miR-199a-5p and miR-199b-5p, as prognostic factors in clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: The expression of DDR1 in tumor and normal renal tissues of 56 patients with ccRCC was assessed by reverse transcription quantitative polymerase chain reaction, western blotting and immunohistochemistry. Renal cancer cells were transfected with specific RNA sequences to validate DDR1 as a putative miR-199a/b-5p target. RESULTS: Decreased DDR1 mRNA and protein, as well as miR-199a/b-5p levels were found in ccRCC. Low DDR1 protein was associated with higher nuclear grade and shorter overall survival. DDR1 immunoreactivity was elevated in the nuclei and unchanged in the membrane/cytoplasmic compartment of tumor cells. DDR1 levels correlated with those of miR-199a/b-5p. In addition, we validated DDR1 as a target gene for miR-199a/b-5p in renal cancer cell lines. CONCLUSION: DDR1 expression is altered in ccRCC, but our findings do not support its oncogenic role. In-depth investigation will be necessary to elucidate the exact role and potential utility of miR-199a/b-5p in ccRCC. Copyright
BACKGROUND/AIM: Accumulating evidence suggests that discoidin domain receptor tyrosine kinase 1 (DDR1) has an oncogenic role. Therefore, the aim of this study was to evaluate the potential utility of DDR1 and its post-transcriptional repressors, miR-199a-5p and miR-199b-5p, as prognostic factors in clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: The expression of DDR1 in tumor and normal renal tissues of 56 patients with ccRCC was assessed by reverse transcription quantitative polymerase chain reaction, western blotting and immunohistochemistry. Renal cancer cells were transfected with specific RNA sequences to validate DDR1 as a putative miR-199a/b-5p target. RESULTS: Decreased DDR1 mRNA and protein, as well as miR-199a/b-5p levels were found in ccRCC. Low DDR1 protein was associated with higher nuclear grade and shorter overall survival. DDR1 immunoreactivity was elevated in the nuclei and unchanged in the membrane/cytoplasmic compartment of tumor cells. DDR1 levels correlated with those of miR-199a/b-5p. In addition, we validated DDR1 as a target gene for miR-199a/b-5p in renal cancer cell lines. CONCLUSION:DDR1 expression is altered in ccRCC, but our findings do not support its oncogenic role. In-depth investigation will be necessary to elucidate the exact role and potential utility of miR-199a/b-5p in ccRCC. Copyright
Authors: Dong Won Baek; Gyeonghwa Kim; Byung Woog Kang; Hye Jin Kim; Su Yeon Park; Jun Seok Park; Gyu-Seog Choi; Min Kyu Kang; Keun Hur; Jong Gwang Kim Journal: J Cancer Res Clin Oncol Date: 2019-11-28 Impact factor: 4.553