Knockdown of DEAD-box RNA helicase 52 (DDX52) suppresses the proliferation of melanoma cells in vitro and of nude mouse xenografts by targeting c-Myc

Abstract

The ATP-dependent protein DEAD-box RNA helicase 52 (DDX52) is an important regulator in RNA biology and has been implicated in the development of prostate and lung cancer. However, its biological functions and clinical importance in malignant melanoma (MM) are still unclear. Understanding the potential mechanism underlying the regulation of MM progression by DDX52 might lead to novel therapeutic strategies. The aim of the present study was to investigate the role of DDX52 in the regulation of MM progression and its clinical relevance. DDX52 expression in normal and MM tissues was evaluated by GEO analysis and immunohistochemistry. The effects of DDX52 on cell growth were evaluated in MM cells with downregulated DDX52 expression. In this study, we found that DDX52 was markedly overexpressed in MM tissues compared with nontumor tissues and was associated with shorter overall survival in patients; therefore, DDX52 might be a prognostic marker in MM. Downregulation of DDX52 expression in the MM cell lines A2058 and MV3 markedly inhibited cell proliferation and colony formation. Additionally, knockdown of DDX52 in MM cells caused significant regression of established tumors in nude mice and delayed the onset time. Moreover, downregulation of DDX52 markedly suppressed c-Myc mRNA and protein expression, and an RNA immunoprecipitation assay confirmed the association between DDX52 and c-Myc. Restoration of c-Myc expression partly rescued the effects of DDX52 deficiency in MM cells. In conclusion, our study found that DDX52 mediated oncogenesis by promoting the transcriptional activity of c-Myc and could be a therapeutic target in MM.

TRIP13/FLNA Complex Promotes Tumor Progression and Is Associated with Unfavorable Outcomes in Melanoma

“…Western blotting was performed as previously described [ 16 ]. Briefly, melanoma cells were lysed, and 30 μ g protein from each sample was separated by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis and transferred to a polyvinylidene difluoride membrane that was blocked with 5% bovine serum albumin and incubated with primary antibodies against glyceraldehyde 3-phosphate dehydrogenase (GAPDH; #5174, 1 : 1000), protein kinase B (AKT; #4685, 1 : 1000), and phosphorylated (p-)AKT (#4060S, 1 : 1000) (all from Cell Signaling Technology, Danvers, MA, USA); TRIP13 (sc-514314, 1 : 1000), E-cadherin (sc-8426, 1 : 1000), and FLNA (sc-17749, 1 : 1000) (all from Santa Cruz Biotechnology); and N-cadherin (ab18203, 1 μ g/ml; Abcam).…”

Protein tyrosine phosphatase 1B(PTP1B) promotes melanoma cells progression through Src activation

“…The tissue microarray was obtained from Xi’an Alenabio.com (China), and detailed information on this microarray has been previously described [ 24 ].…”

Fermitin family homolog 2 (Kindlin-2) affects vascularization during the wound healing process by regulating the Wnt/β-catenin signaling pathway in vascular endothelial cells

“…The mouse wound tissues were weighed and lysed in RIPA buffer with inhibitors and quantified by BAC as previously described [ 20 ]. Then, the lysates were subjected to SDS-PAGE followed by transfer onto a PVDF membrane.…”