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

Jeong Seon Kim, Eun Ju Kim, Sieun Lee, Xiaochao Tan, Xin Liu, Sanghui Park, Keunsoo Kang, Jung Sook Yoon, Yoon Ho Ko, Jonathan M. Kurie, Young Ho Ahn

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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.

Original languageEnglish
Article number9
JournalExperimental and Molecular Medicine
Volume51
Issue number1
DOIs
StatePublished - 1 Jan 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

Fingerprint

Dive into the research topics of 'MiR-34a and miR-34b/c have distinct effects on the suppression of lung adenocarcinomas'. Together they form a unique fingerprint.

Cite this