MicroRNA-222 regulates cell invasion by targeting matrix metalloproteinase 1 (MMP1) and manganese superoxide dismutase 2 (SOD2) in tongue squamous cell carcinoma cell lines.
MicroRNA-222 regulates cell invasion by targeting matrix metalloproteinase 1 (MMP1) and manganese superoxide dismutase 2 (SOD2) in tongue squamous cell carcinoma cell lines.
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发表时间：
2009-05
影响因子：
2.5
通讯作者：
Xiqiang Liu;Jinsheng Yu;Lu Jiang;Anxun Wang;Fei Shi;Hui Ye;Xiaofeng Zhou
中科院分区：
文献类型：
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作者：
Xiqiang Liu;Jinsheng Yu;Lu Jiang;Anxun Wang;Fei Shi;Hui Ye;Xiaofeng Zhou
MicroRNA失调参与肿瘤的发生和发展。本研究的目的是鉴定和验证有助于口腔舌鳞癌（OTSCC）转移的候选microRNA。利用微阵列技术，在具有不同转移潜力的配对OTSCC细胞系中鉴定了一组差异表达的microrna。选择的候选microRNA（包括hsa-miR-222）使用定量PCR方法进一步验证。功能分析表明，hsa-miR-222抑制OTSCC细胞侵袭。异位转染hsa-miR-222可降低OTSCC细胞系中MMP1和SOD2的表达。利用荧光素酶报告基因检测证实了hsa-miR-222直接靶向位于MMP1和SOD2 mrna 3'-非翻译区域的特定序列。此外，siRNA敲低SOD2可导致MMP1表达下调。综上所述，这些结果表明hsa-miR-222通过直接顺式调控机制（靶向MMP1 mRNA）和间接反式调控机制（通过靶向SOD2间接控制MMP1基因表达）调控MMP1的表达。我们的研究结果表明，hsa-miR-222在OTSCC侵袭中起着重要作用，可能成为有转移性疾病风险的OTSCC患者的新治疗靶点。
MicroRNA deregulation is involved in tumor initiation and progression. The aim of this study was to identify and validate the microRNA candidates that contribute to the metastasis of oral tongue squamous cell carcinoma (OTSCC). Using microarrays, a panel of differentially expressed microRNAs was identified in paired OTSCC cell lines with different metastatic potential. Selected microRNA candidates (including hsa-miR-222) were further validated using quantitative PCR approach. Functional analysis indicated that hsa-miR-222 inhibits OTSCC cell invasion. Ectopic transfection of hsa-miR-222 reduced the expression of MMP1 and SOD2 in OTSCC cell lines. Direct targeting of hsa-miR-222 to specific sequences located in the 3'-untranslated regions of both MMP1 and SOD2 mRNAs were confirmed using luciferase reporter gene assays. Furthermore, SOD2 knockdown by siRNA led to the downregulation of MMP1 expression. Taken together, these results suggested that hsa-miR-222 regulates the MMP1 expression through both direct cis-regulatory mechanism (targeting MMP1 mRNA) and indirect trans-regulatory mechanism (indirect controlling of MMP1 gene expression by targeting SOD2). Our results indicate that hsa-miR-222 plays an important role in OTSCC invasion, and may serve as a novel therapeutic target for OTSCC patients at risk of metastatic disease.