Kang Jaeku, Lee Soo Young, Lee Sun Young, Kim Young Jin, Park Jae Yong, Kwon Sun Jung, Na Moon Jun, Lee Eun Jin, Jeon Hyo Sung, Son Ji Woong
Department of Pharmacology, College of Medicine;
Exp Ther Med. 2012 Jan;3(1):149-153. doi: 10.3892/etm.2011.366. Epub 2011 Oct 14.
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.
微小RNA（miRNA）通过调节原癌基因或肿瘤抑制基因的表达，在癌症的发生和发展中发挥重要作用。我们之前使用微阵列进行的研究表明，miR-99b在肺癌患者中表达下调。为了评估miR-99b在肺癌中是否具有功能作用，我们检测了人肺癌组织中miR-99b和成纤维细胞生长因子受体3（FGFR3）的表达，FGFR3是公共算法中miR-99b的预测靶点。在肺癌患者中，miR-99b表达下调，FGFR3表达上调。我们证明miR-99b的过表达导致FGFR3表达降低，并通过荧光素酶报告基因检测证实了miR-99b与FGFR3 3'-非翻译区之间的靶标特异性。此外，与阴性对照相比，用miR-99b前体处理的细胞生长速率较低。综上所述，这些结果表明miR-99b可能通过下调FGFR3而成为一种肿瘤抑制因子。miR-99b可能是一种有效的肿瘤抑制因子，可能成为肺癌患者的潜在治疗工具。
