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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 Seon; Kim, Eun Ju; Lee, Sieun; Tan, Xiaochao; Liu, Xin; Park, Sanghui; Kang, Keunsoo; Yoon, Jung-Sook; Ko, Yoon Ho; Kurie, Jonathan M.; Ahn, Young-Ho
- Ewha Authors
- 박상희; 안영호
- SCOPUS Author ID
- 박상희; 안영호
- Issue Date
- 2019
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- ISSN
- 1226-3613
2092-6413
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE vol. 51
- Publisher
- NATURE PUBLISHING GROUP
- Indexed
- SCIE; SCOPUS; KCI
- 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
- Files in This Item:
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