The expression of RNA helicase DDX5 is transcriptionally upregulated by calcitriol through a vitamin D response element in the proximal promoter in SiHa cervical cells

Abstract

The DEAD box RNA helicase DDX5 is a multifunctional protein involved in the regulatory events of gene expression. Herein, we presented evidence indicating that DDX5 is transcriptionally upregulated by calcitriol, the hormonal form of vitamin D3. In silico analysis revealed the presence of two putative vitamin D response elements (VDREs) in the DDX5 promoter region. Using luciferase reporter assays, we demonstrated that the DDX5 promoter containing these putative VDREs significantly increased the luciferase activity in vitamin D receptor (VDR)-positive SiHa cells upon calcitriol treatment. Electrophoretic mobility shift assays showed the ability of VDR and retinoid X receptor to interact only with the most proximal VDRE, while chromatin immunoprecipitation analysis confirmed the occupancy of this VDRE by the VDR. Finally, we demonstrated that calcitriol significantly increased both DDX5 mRNA and protein in SiHa cells. In summary, this study shows that DDX5 gene is transcriptionally upregulated by calcitriol through a VDRE located in its proximal promoter. Given the importance of DDX5 as a master regulator of differentiation programs, our study suggests that the pro-differentiating properties of calcitriol may be related with the induction of DDX5.

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

“…61 p68 is upregulated in SiHa cervical carcinoma cells in response to treatment with calcitriol (vitamin D3). 62 p68 overexpression may enhance β-catenin and androgen receptor signaling to promote cell proliferation in prostate and non-small-cell lung cancer cells. 63,64 p68 acts as a co-activator of p53 and upregulates the expression of the oncogenic protein kinase, polo-like kinase 1 (PLK1) in the absence of functional p53, which in turn promotes mitosis in various cancers.…”

25-Hydroxycholecalciferol Inhibits Cell Growth and Induces Apoptosis in SiHa Cervical Cells via Autocrine Vitamin D Metabolism

“…A balance favouring pro-apoptotic protein synthesis and activation may mediate our observed finding of intrinsic apoptosis in SiHa 25(OH)D3-treated cells. Other regulatory molecular mechanisms contributing to the anticancer action of 1,25(OH)D3′s in cervical cancer cells include the downregulation of oncogenic voltage channels [ 52 ], upregulation of DDX5 RNA helicase action [ 58 ], and increased biogenesis of microRNAs regulating cancer pathways [ 59 ]. Collectively, these studies support the potential therapeutic application of precursor vitamin D metabolites (cholecalciferol, 25(OH)D3) and 1,25(OH)D3) in the clinical management of cervical cancer by targeting induction of apoptosis and other antitumorigenic mechanisms.…”

Transcriptome profiling of human oocytes experiencing recurrent total fertilization failure

“…Furthermore, during oocyte maturation, it also needs to accumulate sufficient maternal RNA to ensure oocyte maturation, fertilization and subsequently embryo development until the embryonic genome is activated 40 . So certain RNA processing genes identified in Poly-PN zygotes, such as those encoding splicing factor genes THOC1 41 , SF3B1 42 , LOC645691 , exon junction complex core component related gene ( MAGOHB ) 43 , PHD finger-like domain-containing protein 5 A ( PHF5A ) 44 , some pre-mRNA processing factor 18 related gene ( PRPF18 ) 45 and RNA helicases related genes ( DDX5 and BAT1 ) 46,47 , are involved in regulating RNA secondary structure and pre-mRNA splicing, which might be responsible for RNA maturation during oocyte meiosis.…”