MEG3 affects the progression and chemoresistance of T‐cell lymphoblastic lymphoma by suppressing epithelial‐mesenchymal transition via the PI3K/mTOR pathway

Autor: Rui Deng, Fang Liu, Fangyi Fan, Guang-Cui He, Hao-Ping Sun, Yi Su, Hai Yi
Rok vydání: 2018
Předmět:
Zdroj: Journal of Cellular Biochemistry. 120:8144-8153
ISSN: 1097-4644
0730-2312
Popis: Long noncoding RNAs (lncRNA) are emerging as integral functional and regulatory components in the development of different diseases including cancer. Maternally expressed gene 3 (MEG3), is a lncRNA, that has a depressed expression in multiple tumor types, including T-cell lymphoblastic lymphoma (T-LBL). However, the molecular mechanisms that regulate the tumorigenic functions of MEG3 in T-LBL remain largely unknown. In this study, we aimed to discover and identify the function of MEG3 in T-LBL tumorigenesis, epithelial-mesenchymal transition (EMT) and drug resistance, and explore their mechanisms of action. Knockdown MEG3 promoted the proliferation, migration, invasion, and drug resistance of T-LBL cells while overexpression of MEG3 gets the opposite results. The mechanism study showed that decreased MEG3 expression in T-LBL cells could activate PI3K/mTOR signaling pathways, increase the expression of p-glycoprotein and affect the expression of EMT markers for transforming to mesenchymal cells in vitro and in vivo. Together, these results indicate that MEG3 could inhibit the migration, invasion, and drug resistance in T-LBL cells by suppression of the PI3K/mTOR pathway. MEG3 might be a potential target, through which poor prognosis with high recurrence and drug resistance of T-LBL in a clinical setting could be reversed.
Databáze: OpenAIRE
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