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
Rok vydání: 2017
Předmět:
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