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Lnc-THOR silencing inhibits human glioma cell survival by activating MAGEA6-AMPK signaling

Authors :
Bomin Sun
Qingfang Sun
Liang-Yun Hu
Si-Jian Pan
Shan Zhong
Jun Xue
Source :
Cell Death & Disease, Cell Death and Disease, Vol 10, Iss 11, Pp 1-13 (2019)
Publication Year :
2019
Publisher :
Springer Science and Business Media LLC, 2019.

Abstract

Long non-coding RNA THOR (Lnc-THOR) binds to IGF2BP1, essential for its function. We here show that Lnc-THOR is expressed in human glioma tissues and cells. Its expression is extremely low or even undetected in normal brain tissues, as well as in human neuronal cells and astrocytes. We show that Lnc-THOR directly binds to IGF2BP1 in established and primary human glioma cells. shRNA-mediated Lnc-THOR knockdown or CRISPR/Cas9-induced Lnc-THOR knockout potently inhibited cell survival and proliferation, while provoking glioma cell apoptosis. Contrarily, forced overexpression of Lnc-THOR promoted glioma cell growth and migration. Importantly, Lnc-THOR shRNA or knockout activated MAGEA6-AMPK signaling in glioma cells. AMPK inactivation, by AMPKα1 shRNA, knockout, or dominant-negative mutation (T172A), attenuated Lnc-THOR shRNA-induced A172 glioma cell apoptosis. Moreover, CRISPR/Cas9-induced IGF2BP1 knockout activated MAGEA6-AMPK signaling as well, causing A172 glioma cell apoptosis. Significantly, Lnc-THOR shRNA was ineffective in IGF2BP1 KO A172 cells. In vivo, Lnc-THOR silencing or knockout potently inhibited subcutaneous A172 xenograft tumor growth in mice. MAGEA6 downregulation and AMPK activation were detected in Lnc-THOR-silenced/-KO A172 tumor tissues. Taken together, Lnc-THOR depletion inhibits human glioma cell survival possibly by activating MAGEA6-AMPK signaling.

Details

ISSN :
20414889
Volume :
10
Database :
OpenAIRE
Journal :
Cell Death & Disease
Accession number :
edsair.doi.dedup.....193f675b0c107ea7ea6f9d3a73f02b0a