DLX5 promotes osteosarcoma progression via activation of the NOTCH signaling pathway

Am J Cancer Res. 2021 Jun 15;11(6):3354-3374. eCollection 2021.ABSTRACTThe distal-less (dlx) homeobox transcription factors have been implicated roles in bone development. DLX5, in particular, was shown to play essential roles in osteoblast differentiation by targeting RUNX2, a master transcription factor for bone development. Interestingly, DLX5 has also been shown to play an oncogenic role in lung and other cancers, possibly via regulation of MYC expression. Given its dual roles in bone and cancer, this study aimed to investigate the effect of DLX5 on progression of osteosarcoma (OS), the primary bone cancer that is characterized by abnormal bone formation and osteoblast activity. Expression of DLX5 in OS cell lines was detected by quantitative real-time PCR (qRT-PCR) and western blot (WB). In vitro and in vivo assays were performed to investigate the oncogenic function of DLX5 in OS cells and xenograft models. Luciferase reporter assay was performed to determine the underlying mechanism of DLX5-mediated OS aggressiveness. The results showed that DLX5 was differentially expressed in OS cell lines, with significantly upregulated levels in HOS and MG-63 and relatively low levels in U2OS and 143B cell lines, compared with the normal bone cell line. DLX5 knockdown in HOS and MG-63 cell lines by siRNA inhibited OS cell growth and progression, and induced cell apoptosis and cell cycle changes both in vitro and in vivo. Meanwhile, DLX5 overexpression had the opposite effect on U2O...
Source: Cell Research - Category: Cytology Authors: Source Type: research