MicroRNA-99b acts as a tumor suppressor in non-small cell lung cancer by directly targeting fibroblast growth factor receptor 3

Department of Pharmacology, College of Medicine
Experimental and therapeutic medicine (Impact Factor: 0.94). 01/2012; 3(1):149-153. DOI: 10.3892/etm.2011.366
Source: PubMed

ABSTRACT microRNAs (miRNAs) play a significant role in cancer development and progression by regulating the expression of proto-oncogenes or tumor suppressor genes. Our previous study using microarrays demonstrated that miR-99b was downregulated in patients with lung cancer. To assess whether or not miR-99b has a functional role in lung cancer, we determined the expression of miR-99b and fibroblast growth factor receptor 3 (FGFR3), which is a predicted target of miR-99b in public algorithms in human lung cancer tissues. miR-99b was downregulated and FGFR3 was upregulated in lung cancer patients. We demonstrated that the overexpression of miR-99b induced a reduction in FGFR3 expression and confirmed the target specificity between miR-99b and the FGFR3 3'-untranslated region by luciferase reporter assay. In addition, the growth rate in miR-99b precursor-treated cells was lower compared to the negative controls. Taken together, these results suggest that miR-99b may be a tumor suppressor through the downregulation of FGFR3. miR-99b may be a potent tumor suppressor and may be a potential therapeutic tool for patients with lung cancer.

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    • "Additional therapeutic targets that were indicated by TCGA study are the fibroblast growth factor receptors (FGFRs). While FGFRs were not highlighted by our analyses, we note that the miRNA that we observed to have undergone the largest fold changes in expression was somewhat enriched for miR-99 family members and that a direct association between hsa-miR-99b [ENSG0000007550], acting as a tumor suppressor in non–small cell lung cancer, and FGFR3 [ENSG00000068078] has been observed [86]. A study of 183 lung adenocarcinomas that reported the findings of genome and exome sequencing data analysis was also published [91]. "
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