Oncogenetic natural antisense transcript, PTB-AS, promotes glioma cancer by elevating the expression of PTB

• 1、State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
• 2、Department of Neurosurgery, Beijing Tiantan Hospital, Beijing 100050, China

Abstract：Glioma is the most common primary malignancy in the brain, which has the high recurrence and lethality rate, and it's imminent to explore the molecular mechanism of this incurable disease. Poly-pyrimidine tract binding protein (PTB, also known as PTBP1) is a kind of RNA-binding protein with various molecular functions and plays an indispensable role in glioma. Since research about the regulation of PTB is limited in microRNAs and transcription factors, here we want to explore the new lncRNA regulators of PTB in order to consummate the principle of controlling the PTB expression and further reveal the molecular mechanism of accommodating glioma tumorigenesis. We identify a novel natural antisense transcript of PTB named PTB-AS and find that the expression of PTB-AS in glioma is significantly directly correlated with PTB-mRNA. Naturally, knocking down the abundance of PTB-AS in glioma can remarkably reduce the expression of PTB mRNA and protein. Then we validate the important function of PTB-AS in glioma for the first time and discover the original fact that PTB-AS influence the stability of PTB-mRNA by directly binding to PTB-3'UTR, what's more, it's the latest finding to demonstrate that miR-9 can negatively regulate PTB in human cancer and in practice PTB-AS could elevate the expression of PTB by masking the binding site of miR-9 in PTB-3'UTR so as to maintain the high expression level of PTB, miR-9 and itself in glioma.

keywords： Natural antisense transcript (NAT), PTB, miR-9, glioma, post-transcriptional regulation, LncRNAs.

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