Rola Saleeb1, Sung Sun Kim2, Qiang Ding3, Andreas Scorilas4, Sicheng Lin1, Heba Wz Khella1, Carl Boulos5, Gena Ibrahim1, George M Yousef6. 1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. 2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada; Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea. 3. Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada. 4. Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece. 5. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada. 6. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada. Electronic address: George.yousef@sickkids.ca.
Abstract
OBJECTIVES: microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by mRNA cleavage or translational repression. The miR-200 family is involved in the regulation of various tumor biologic processes including apoptosis, proliferation, invasion, and metastasis. They function mainly as tumor suppressors. In this study, we aim to validate the prognostic significance of miR-200 family using large cohort of primary clear cell renal cell carcinoma (ccRCC) and matched normal tissue and to explore the role of miR-200 family in RCC pathogenesis and progression. MATERIALS AND METHODS: We analyzed the expression of 3 members of the miR-200 family; miR-141, miR-200b, and miR-200c, between primary ccRCC, matched normal renal tissues, and nonmatched metastatic RCC. We compared clinicopathologic parameter including disease-free survival to miR-200 family expression. Additionally, we validated our results using The Cancer Genome Atlas dataset. We explored functional role of these miRNAs by bioinformatics analyses. RESULTS AND CONCLUSIONS: Expression of miR-200 family significantly decreased in cancer compared to non-neoplastic tissues. miR-141 and miR-200b were significantly down-regulated in metastatic than primary tumors. There was statistically significant negative association between all 3 miRNAs and tumor size and stage. As binary variables, univariate analyses revealed that miR-141, miR-200b, and miR-200c-positive ccRCC patients have a statistically significant lower chance of disease-recurrence or relapse and multivariate analyses showed miR-200b and miR-200c-positive patients have longer disease-free survival. We could predict disease-free survival better when 2 or more miRNAs were used as a combination. Overall survival analysis using The Cancer Genome Atlas data revealed that miR-200b-positive patients have significantly better survival. These results suggest that miR-141, miR-200b, and miR-200c are independent prognostic markers for ccRCC. Targets of these miRNAs are associated with pathways related to cancer invasion and metastasis, including TRAIL pathway, VEGF and VEGFR signaling network, and epithelial-mesenchymal transition.
OBJECTIVES: microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by mRNA cleavage or translational repression. The miR-200 family is involved in the regulation of various tumor biologic processes including apoptosis, proliferation, invasion, and metastasis. They function mainly as tumor suppressors. In this study, we aim to validate the prognostic significance of miR-200 family using large cohort of primary clear cell renal cell carcinoma (ccRCC) and matched normal tissue and to explore the role of miR-200 family in RCC pathogenesis and progression. MATERIALS AND METHODS: We analyzed the expression of 3 members of the miR-200 family; miR-141, miR-200b, and miR-200c, between primary ccRCC, matched normal renal tissues, and nonmatched metastatic RCC. We compared clinicopathologic parameter including disease-free survival to miR-200 family expression. Additionally, we validated our results using The Cancer Genome Atlas dataset. We explored functional role of these miRNAs by bioinformatics analyses. RESULTS AND CONCLUSIONS: Expression of miR-200 family significantly decreased in cancer compared to non-neoplastic tissues. miR-141 and miR-200b were significantly down-regulated in metastatic than primary tumors. There was statistically significant negative association between all 3 miRNAs and tumor size and stage. As binary variables, univariate analyses revealed that miR-141, miR-200b, and miR-200c-positive ccRCCpatients have a statistically significant lower chance of disease-recurrence or relapse and multivariate analyses showed miR-200b and miR-200c-positive patients have longer disease-free survival. We could predict disease-free survival better when 2 or more miRNAs were used as a combination. Overall survival analysis using The Cancer Genome Atlas data revealed that miR-200b-positive patients have significantly better survival. These results suggest that miR-141, miR-200b, and miR-200c are independent prognostic markers for ccRCC. Targets of these miRNAs are associated with pathways related to cancer invasion and metastasis, including TRAIL pathway, VEGF and VEGFR signaling network, and epithelial-mesenchymal transition.
Authors: Sergio Romera-Giner; Zoraida Andreu Martínez; Francisco García-García; Marta R Hidalgo Journal: Biol Direct Date: 2021-05-26 Impact factor: 4.540
Authors: Przemysław A Stempor; Dror Avni; Raya Leibowitz; Yechezkel Sidi; Maria Stępień; Tomasz Dzieciątkowski; Paula Dobosz Journal: Int J Mol Sci Date: 2021-03-04 Impact factor: 5.923