The Study Of Glioma MiRNA Profile And The Role Of MiR-31on Glioma

Glioma is the most common and aggressive primary brain tumor and the first cancer studied by The Cancer Genome Atlas (TCGA). The annual incidence of malignant gliomas is approximately5cases per100,000people. Despite with aggressive surgery, radiation, and chemotherapy, the median survival is only12to15months for glioblastomas. miRNAs are a novel group of short RNAs, about20～22nucleotide in length, that regulate gene expression in a posttranscriptional manner by affecting the stability or translation of mRNAs. It is becoming increasingly clear that altered miRNA expression correlates with the pathogenesis of glioma.In the first section, we use deep sequencing to explore the profiling of glioblastomas and normal brain tissue. We find778and743known miRNA/miRNA*in glioblastomas and normal brain tissue, respectively. The abundance of miRNAs varies from several to hundreds of thousands and more than50%of them are in a low abundance with counts less than10TPM.44miRNA/miRNA*are differentially expressed.20of them are up-regulated in glioma including miR-21which is well known as oncomiR, while24of them are down-regulated. Using miR-10b, miR-31and miR-92b as examples, we utilized QRT-PCR method to verify the sequencing results in another7normal brain tissues and10glioma samples. The QRT-PCR results indicated good consistency with the results of sequencing method. In addition, we also find21novel miRNA and20miRNA*form of known miRNA in glioma and normal brain tissue. Most of the miRNA have several isomiRs.In the second section, we studied the role and mechanism of miR-31in glioblastomas. miR-31locates in9p21.3in human genome. It had been reported that miR-31is dysregulated in several types of cancer including colon, breast, prostate, gastric and lung cancers. It has both positive and negative effects on cancer depending on the organ. In breast cancer, miR-31could inhibit metastasis by targeting ITGAR, RDX and RhoA. But in lung cancer, it acted as an oncogenic miRNA by repressing tumor suppressors (LATS2and PPP2R2A). In colon carcinoma cells, miR-31 expression is regulated by TGF-beta and it targets TIAM1to regulate migration and invasion. In order to study the role of miR-31in glioma, we ectopically expressed miR-31in U251glioma cell to produce U251-Mir-31cell. Functional study showed miR-31could inhibit U251in migration and invasion, but not in proliferation. We also verified that RDX is a direct target of miR-31in glioma. Microarray data showed that miR-31could regulate many metastasis related genes.