title: FBXL10 contributes to the progression of nasopharyngeal carcinoma via involving in PI3K/mTOR pathway.
abstract: Our study aimed to investigate whether F-box and leucine-rich repeat protein 10 (FBXL10) may play a pivotal role in nasopharyngeal carcinoma (NPC) development via involving in PI3K/mTOR pathway. We .constructed an FBXL10 expression vector (pcDNA3.1-FBXL10). Then pcDNA3.1-FBXL10 and FBXL10-specific siRNA (siFBXL10) were transfected into human NPC cell line CNE1 and SUNE1 with Lipofectamine ® 2000. Moreover, cells were treated with PI3K inhibitor BEZ235. Besides, MTT assay and flow cytometry were respectively used to explore cell proliferation and apoptosis in vitro. Finally, the expression of key proteins involved in PI3K/AKT/mTOR pathway, such as P-AKT, AKT, P-P70, P70, P-Myc and Myc, were determined by western blot. Western blot analysis displayed that FBXL10 was overexpressed and suppressed after transfected by pcDNA3.1-FBXL10 and siFBXL10, respectively. Moreover, cell proliferation in FBXL10 overexpression group gradually increased compared with control group while obviously decreased in siFBXL10 group. Moreover, volume of apoptotic cells significantly increased with knockdown of FBXL10, which was similar with BEZ235 treatment. Besides, knockdown of FBXL10 decreased the expression levels of PI3K/mTOR pathway-related proteins, which was also similar with BEZ235 treatment. Notably, BEZ235 and siFBXL10 treatment induced significant increase of cell apoptosis and decrease of the expression levels of PI3K/mTOR pathway-related proteins than that only treated with siFBXL10. These findings indicate that FBXL10 may play a pivotal role in promoting cell proliferation and inhibiting cell apoptosis in NPC cells via targeting or functioning synergistically with PI3K/mTOR pathway. Knockdown of FBXL10 may be a novel therapeutic strategy for the treatment of NPC.
authors.forename: Y
authors.initials: Y
authors.lastname: Ren
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: M
authors.initials: M
authors.lastname: Zhang
keywords: BEZ235; F-box and leucine-rich repeat protein 10; PI3K/mTOR pathway.; nasopharyngeal carcinoma