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

• Published in: Journal of cellular biochemistry 2019-05, Vol.120 (5), p.8144-8153
• Main Authors: Deng, Rui, Fan, Fang‐Yi, Yi, Hai, Liu, Fang, He, Guang‐Cui, Sun, Hao‐Ping, Su, Yi
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Cancer; Cell proliferation; Chemoresistance; Drug resistance; epithelial‐mesenchymal transition; Gene expression; Glycoproteins; invasion; long noncoding RNA; Lymphoma; maternally expressed gene 3; Mesenchyme; migration; Molecular modelling; TOR protein; Tumorigenesis; T‐cell lymphoblastic lymphoma
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28093

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. Long noncoding RNAs (lncRNAs) 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 and drug resistance, and explore their mechanisms of action.