Details

Autor(en) / Beteiligte

• Jia, Lei
• Song, Yuwen
• Mu, Luyan
• Li, Qingla
• Tang, Jiabin
• Yang, Zhao
• Meng, Wenjuan

Titel

Long noncoding RNA TPT1‐AS1 downregulates the microRNA‐770‐5p expression to inhibit glioma cell autophagy and promote proliferation through STMN1 upregulation

Ist Teil von

• Journal of cellular physiology, 2020-04, Vol.235 (4), p.3679-3689

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. A schematic diagram depicts molecular mechanism of TPT1‐AS1/miR‐770‐5p/STMN1 axis regulating glioma proliferation and autophagy. TPT1‐AS1 acts to decrease microRNA‐770‐5p (miR‐770‐5p) expression and then promotes the expression of stathmin 1 (STMN1), ultimately inhibiting autophagy but promoting proliferation of glioma.