%0 Journal Article
%T Molecular mechanism of FBXW7-mediated ubiquitination modification in nasopharyngeal carcinoma cell proliferation in vitro and in vivo.
%A Zhong Q
%A Wang Z
%A Kang H
%A Wu R
%J Pathol Res Pract
%V 244
%N 0
%D Apr 2023
%M 36989847
%F 3.309
%R 10.1016/j.prp.2022.154056
%X <B>OBJECTIVE: </B>Nasopharyngeal carcinoma (NPC) is a type of keratinizing squamous cell malignancy. Ubiquitination, a common protein posttranslational modification, participates in cancer development. This study sought to investigate the mechanism of F-box and WD repeat domain containing 7 (FBXW7) in NPC cell proliferation in vivo and in vitro.<BR><B>METHODS: </B>FBXW7, Homeobox A10 (HOXA10), and bone morphogenetic protein-2 (BMP2) expression levels in NPC tissues and cells were detected by RT-qPCR and Western blotting. Cell proliferation was assessed by cell counting kit-8 and colony formation assays. The binding of FBXW7 to HOXA10 and HOXA10 ubiquitination level were detected via co-immunoprecipitation and ubiquitination assay. Cells were treated with MG132 (the proteasome inhibitor), followed by the determination of HOXA10 ubiquitination and protein levels. The binding of HOXA10 to BMP2 was testified via dual-luciferase and chromatin immunoprecipitation assays. Collaborative experiments were performed to confirm the role of HOXA10 or BMP2 in FBXW7-mediated NPC cell proliferation. Xenograft tumor assay was performed to confirm the role of FBXW7/HOXA10/BMP2 in vivo.<BR><B>RESULTS: </B>FBXW7 was under-expressed, while HOXA10 and BMP2 were up-expressed in NPC tissues and cells. FBXW7 overexpression restricted NPC cell proliferation. Mechanically, FBXW7 bound to HOXA10 to promote ubiquitination-based degradation of HOXA10 and further reduced the binding of HOXA10 to the BMP2 promoter and inhibited BMP2 transcription. Overexpression of HOXA10 or BMP2 attenuated the role of FBXW7 overexpression in inhibiting NPC cell proliferation. FBXW7 overexpression reduced Ki67 positive rate and repressed tumor growth.<BR><B>CONCLUSIONS: </B>FBXW7 overexpression promoted HOXA10 ubiquitination-based degradation and further inhibited BMP2 transcription, consequently restricting NPC cell proliferation in vitro and in vivo.