The association between miR-34 dysregulation and distant metastases formation in lung adenocarcinoma
Autor: | Alice Knudsen, Henrik Hager, Lise Lotte Hansen, Iben Daugaard, Tina E Kjeldsen |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Lung Neoplasms Clinical Biochemistry Adenocarcinoma of Lung Biology Adenocarcinoma Pathology and Forensic Medicine Metastasis 03 medical and health sciences 0302 clinical medicine microRNA medicine Journal Article Humans Neoplasm Metastasis Lung cancer Promoter Regions Genetic Molecular Biology Lung Research Support Non-U.S. Gov't Promoter Methylation DNA Methylation medicine.disease Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis DNA methylation Cancer research |
Zdroj: | Daugaard, I, Knudsen, A, Kjeldsen, T E, Hager, H & Hansen, L L 2017, ' The association between miR-34 dysregulation and distant metastases formation in lung adenocarcinoma ', Experimental and Molecular Pathology, vol. 102, no. 3, pp. 484-491 . https://doi.org/10.1016/j.yexmp.2017.05.012 |
ISSN: | 1096-0945 |
DOI: | 10.1016/j.yexmp.2017.05.012 |
Popis: | Lung cancer has the highest mortality rate amongst human cancers and the majority of deaths can be attributed to metastatic spread. The miR-34 family includes three tumor suppressive miRs: miR-34a, miR-34b and miR-34c. miR-34 downregulation is a frequent observation in human malignancies and is often attributed to hypermethylation of the miR-34a and miR-34b/c promoters. Here, the potential association between aberrant miR-34 expression and promoter methylation and distant metastases formation in lung adenocarcinoma (LAC) is investigated. The expression levels of miR-34a, miR-34b and miR-34c, as well as the methylation status of the miR-34a and miR-34b/c promoters were determined in a LAC patient cohort comprising 26 non-metastasizing and 26 metastasizing primary LACs, as well as 24 paired distant metastases and 25 tumor-adjacent normal lung samples using RT-qPCR and Methylation-Sensitive High Resolution Melting (MS-HRM) analysis. No difference in expression was observed for miR-34a when comparing metastasizing and non-metastasizing LACs (p=0.793). For both miR-34b and miR-34c, a significantly lower expression level was determined in metastasizing LACs compared to non-metastasizing LACs (p=0.0005 and p=0.002) with similarly decreased expression levels observed in the paired distant metastases. Hypermethylation was detected in 35/51 LACs compared to 0/25 tumor-adjacent normal lungs for the miR-34a promoter (p |
Databáze: | OpenAIRE |
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