MiR-34a and miR-34b/c have distinct effects on the suppression of lung adenocarcinomas
- 주제(기타) Biochemistry & Molecular Biology; Medicine, Research & Experimental
- 설명문(일반) [Kim, Jeong Seon; Kim, Eun Ju; Lee, Sieun; Ahn, Young-Ho] Ewha Womans Univ, Dept Mol Med, Coll Med, Seoul 07985, South Korea; [Kim, Jeong Seon; Kim, Eun Ju; Lee, Sieun; Ahn, Young-Ho] Ewha Womans Univ, Coll Med, Tissue Injury Def Res Ctr, Seoul 07985, South Korea; [Tan, Xiaochao; Liu, Xin] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA; [Park, Sanghui] Ewha Womans Univ, Coll Med, Dept Pathol, Seoul 07985, South Korea; [Kang, Keunsoo] Dankook Univ, Dept Microbiol, Coll Nat Sci, Cheonan 31116, Chungnam, South Korea; [Yoon, Jung-Sook; Ko, Yoon Ho] Catholic Univ Korea, Div Oncol, Dept Internal Med, Coll Med, Seoul 06591, South Korea
- OA유형 Green Published, gold
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160275
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s12276-018-0203-1
- PubMed https://pubmed.ncbi.nlm.nih.gov/30700696
초록/요약
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.
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