| Summary: | 碩士 === 國立成功大學 === 口腔醫學研究所 === 97 === MicroRNAs (miRNAs) are endogenous small noncoding RNAs that reduce the translation of mRNAs or cause mRNA degradation by targeting mRNAs. Recent evidences have shown that a number of miRNAs are differentially expressed in various tumors vs. normal tissues and associated with cancer development. MiRNAs change in the amounts of these RNAs can be tumorigenic or tumor suppressive if they target mRNAs for either a tumor suppressor or an oncogene. In the previous study, we found that the expression of miR-320 was lower in oral cancer cells (OC2) than in normal human oral keratinocytes by microarray analyses. In the analysis of clinical OSCC match-pair tissues, we also found that miR-320 were significantly down-regulated in oral cancer specimens. By using the bioinformatic tools at the miRNA target database, neuropilin 1 (NRP1) was predicted to be a target of miR-320. NRP1 plays a central role in neuronal and blood vessel development as a receptor for two ligand types, the semaphorin family of axon guidance modulators and the VEGF family of angiogenesis stimulators. Several studies showed that NRP1 promoted tumor angiogenesis, vascular endothelial cells migration, and tumor metastasis. In this study, we found that miR-320 regulates the expression of NRP1 at a posttranscriptional level by transfecting miR-320 precursor or antagomiR-320 in human umbilical vein endothelial cells (HUVECs). Using luciferase reporter assays we confirmed that miR-320 could reduce luciferase expression by binding 3’ UTR of NRP1. MiR-320 reduced HUVECs migration and adhesion by decreasing expression of NRP1. Furthermore, we found that hypoxia-nutrients deprivation reduced expression of miR-320 and increase NRP1 level in HUVECs. Clinical specimens’ examination by in situ hybridization and immunohistochemistry analyses also showed that miR-320 expression was down-regulated and inversely correlated with NRP1 expression status in the blood vessels of OSCC tissues. Taken together, our present study revealed that miR-320 was down-regulated in cancer-associated vascular endothelial cells and might modulate tumor angiogenesis.
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