| First Author | Dimitrova N | Year | 2016 |
| Journal | Cancer Discov | Volume | 6 |
| Issue | 2 | Pages | 188-201 |
| PubMed ID | 26586766 | Mgi Jnum | J:229235 |
| Mgi Id | MGI:5751308 | Doi | 10.1158/2159-8290.CD-15-0854 |
| Citation | Dimitrova N, et al. (2016) Stromal Expression of miR-143/145 Promotes Neoangiogenesis in Lung Cancer Development. Cancer Discov 6(2):188-201 |
| abstractText | The two unrelated miRNAs miR-143 and miR-145, coexpressed from the miR-143/145 cluster, have been proposed to act as tumor suppressors in human cancer, and therapeutic benefits of delivering miR-143 and miR-145 to tumors have been reported. In contrast, we found that tumor-specific deletion of miR-143/145 in an autochthonous mouse model of lung adenocarcinoma did not affect tumor development. This was consistent with the lack of endogenous miR-143/145 expression in normal and transformed lung epithelium. Surprisingly, miR-143/145 in the tumor microenvironment dramatically promoted tumor growth by stimulating the proliferation of endothelial cells. Loss of miR-143/145 in vivo led to derepression of the miR-145 target CAMK1D, an inhibitory kinase, which when overexpressed prevents mitotic entry of endothelial cells. As a consequence, tumors in miR-143/145-deficient animals exhibited diminished neoangiogenesis, increased apoptosis, and their expansion was limited by the tumor's ability to co-opt the alveolar vasculature. These findings demonstrate that stromal miR-143/145 promotes tumorigenesis and caution against the use of these miRNAs as agents in cancer therapeutics. SIGNIFICANCE: This study shows that miR-143/145 expressed from the tumor microenvironment stimulates neoangiogenesis and supports tumor expansion in the lung, demonstrating a surprising role for the putative tumor suppressor miRNA cluster in promoting tumorigenesis. We propose inhibition of miR-143/145 as a therapeutic avenue to modulate tumor neoangiogenesis. Cancer Discov; 6(2); 188-201. (c)2015 AACR.This article is highlighted in the In This Issue feature, p. 109. |
