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MiR-34a and miR-34b/c have distinct effects on the suppression of lung adenocarcinomas

Title
MiR-34a and miR-34b/c have distinct effects on the suppression of lung adenocarcinomas
Authors
Kim, Jeong SeonKim, Eun JuLee, SieunTan, XiaochaoLiu, XinPark, SanghuiKang, KeunsooYoon, Jung-SookKo, Yoon HoKurie, Jonathan M.Ahn, Young-Ho
Ewha Authors
박상희안영호
SCOPUS Author ID
박상희scopus; 안영호scopus
Issue Date
2019
Journal Title
EXPERIMENTAL AND MOLECULAR MEDICINE
ISSN
1226-3613JCR Link

2092-6413JCR Link
Citation
EXPERIMENTAL AND MOLECULAR MEDICINE vol. 51
Publisher
NATURE PUBLISHING GROUP
Indexed
SCIE; SCOPUS; KCI WOS scopus
Document Type
Article
Abstract
Three miR-34 family members (miR-34a, miR-34b, and miR-34c) are clustered on two different chromosomal loci, Mir34a and Mir34b/c. These miRNAs have identical seed sequences, which are predicted to target the same set of genes. However, miR-34a and miR-34c have different sets of negatively correlated genes in lung adenocarcinoma data from The Cancer Genome Atlas. Therefore, we hypothesized that the individual miR-34 family members, which are tumor suppressive miRNAs, would have varying effects on lung tumorigenesis. To show this, we overexpressed each miR-34 cluster in murine lung cancer cells. MiR-34b/c enhanced cancer cell attachment and suppressed cell growth and invasion compared with miR-34a. In a syngeneic mouse model, both miR-34a and miR-34b/c blocked lung metastasis. However, miR-34b/c suppressed tumor growth more than miR-34a. MiR-34b/c also decreased the expression of mesenchymal markers (Cdh2 and Fn1) and increased the expression of epithelial markers (Cldn3, Dsp, and miR-200) to a greater degree than miR-34a. These results imply that miR-34b and miR-34c inhibit epithelial-to-mesenchymal transition. Furthermore, knockout of all three miR-34 members promoted mutant Kras-driven lung tumor progression in mice. Similarly, lung adenocarcinoma patients with higher miR-34a/b/c levels had better survival rates than did those with lower levels. In summary, we suggest that miR-34b and miR-34c are more effective tumor suppressors than miR-34a.
DOI
10.1038/s12276-018-0203-1
Appears in Collections:
의과대학 > 의학과 > Journal papers
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