Long noncoding RNA TPT1-AS1 downregulates the microRNA-770-5p expression to inhibit glioma cell autophagy and promote proliferation through STMN1 upregulation |
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Authors: | Lei Jia Yuwen Song Luyan Mu Qingla Li Jiabin Tang Zhao Yang Wenjuan Meng |
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Affiliation: | 1. Department of Neurosurgery, The 4th Affiliated Hospital of Harbin Medical University, Harbin, China;2. Department of Minimally Invasive Neurosurgery, The 4th Affiliated Hospital of Harbin Medical University, Harbin, China;3. Department of Comprehensive Archives, The 1st Affiliated Hospital of Harbin Medical University, Harbin, China |
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Abstract: | Through the microarray analysis, long noncoding RNA TPT1-AS1 (TPT1-AS1) was identified in the development of glioma. However, the specific effect of TPT1-AS1 on glioma autophagy in the recent years has not fully been investigated. Therefore, the purpose of our present study is to investigate the function of TPT1-AS1 on affecting autophagy of glioma cells through regulation of microRNA-770-5p (miR-770-5p)-mediated stathmin 1 (STMN1). Initially, the expression of TPT1-AS1, miR-770-5p, and STMN1 were determined in glioma cell lines, followed by the prediction and validation of their interaction. After that, the effects of TPT1-AS1, miR-770-5p, and STMN1 on the in vitro glioma cell proliferation and autophagy were assessed using EdU assay and macrophage-derived chemokine (MDC) and on the in vivo tumor development and autophagy were evaluated using a nude mouse xenograft tumor assay and immunofluorescence assay. In comparison with the normal cells, the glioma cells displayed upregulated expression of TPT1-AS1 and STMN1, but a downregulated miR-770-5p expression. miR-770-5p, which directly targeted STMN1, could be downregulated by TPT1-AS1. Subsequently, in glioma cells, TPT1-AS1 can function to competitively bind to miR-770-5p, thus regulatEing STMN1 expression. Moreover, glioma cell proliferation and autophagy could be mediated through the TPT1-AS1/miR-770-5p/STMN1 axis. From our data we conclude an inhibitory function of TPT1-AS1 in glioma cell autophagy by downregulating miR-770-5p and upregulating STMN1, which may be instrumental for the therapeutic targeting and clinical management of glioma. |
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Keywords: | autophagy glioma long noncoding RNA TPT1-AS1 microRNA-770-5p proliferation stathmin 1 |
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