DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA.

BACKGROUND: The DEAD-box family is essential for tumorigenesis and embryogenesis. Previously, we linked the malfunction of DDX (DEAD-box RNA helicase)-24 to a special type of vascular malformation. Here, we aim to investigate the function of DDX24 in vascular smooth muscle cells (VSMCs) and embryonic vascular development. METHODS: Cardiomyocyte (CMC) and VSMC-specific Ddx24 knockout mice were generated by crossing Tagln-Cre mice with Ddx24flox/flox transgenic mice. The development of blood vessels was explored by stereomicroscope photography and immunofluorescence staining. Flow cytometry and cell proliferation assays were used to verify the regulation of DDX24 on the function of VSMCs. RNA sequencing and RNA immunoprecipitation coupled with quantitative real-time polymerase chain reaction were combined to investigate DDX24 downstream regulatory molecules. RNA pull-down and RNA stability experiments were performed to explore the regulation mechanism of DDX24. RESULTS: CMC/VSMC-specific Ddx24 knockout mice died before embryonic day 13.5 with defects in vessel formation and abnormal vascular remodeling in extraembryonic tissues. Ddx24 knockdown suppressed VSMC proliferation via cell cycle arrest, likely due to increased DNA damage. DDX24 protein bound to and stabilized the mRNA of FANCA (FA complementation group A) that responded to DNA damage. Consistent with the function of DDX24, depletion of FANCA also impacted cell cycle and DNA repair of VSMCs. Overexpression of FANCA was able to rescue the alterations caused by DDX24 deficiency. CONCLUSIONS: Our study unveiled a critical role of DDX24 in VSMC-mediated vascular development, highlighting a potential therapeutic target for VSMC-related pathological conditions.

RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression.

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Elucidating the underlying mechanisms of this disease could provide new therapeutic strategies for treating HCC. Here, we identified a novel role of DEAD-box helicase 24 (DDX24), a member of the DEAD-box protein family, in promoting HCC progression. DDX24 levels were significantly elevated in HCC tissues and were associated with poor prognosis of HCC. Overexpression of DDX24 promoted HCC migration and proliferation in vitro and in vivo, whereas suppression of DDX24 inhibited both functions. Mechanistically, DDX24 bound the mRNA618-624nt of laminin subunit beta 1 (LAMB1) and increased its stability in a manner dependent upon the interaction between nucleolin and the C-terminal region of DDX24. Moreover, regulatory factor X8 (RFX8) was identified as a DDX24 promoter-binding protein that transcriptionally upregulated DDX24 expression. Collectively, these findings demonstrate that the RFX8/DDX24/LAMB1 axis promotes HCC progression, providing potential therapeutic targets for HCC. SIGNIFICANCE: The identification of a tumor-promoting role of DDX24 and the elucidation of the underlying regulatory mechanism provide potential prognostic indicators and therapeutic approaches to help improve the outcome of patients with hepatocellular carcinoma.

Identification of post traumatic stress disorder and risk factors in military first responders 6 months after Wen Chuan earthquake in China.

BACKGROUND: Military personnel commonly serve as first responders to natural disasters. Our aim is to identify Post-Traumatic Stress Disorder (PTSD) and determine risk in military responders to the Wen Chuan earthquake. METHODS: Analyses were carried out on 1056 of the 1125 soldiers enrolled. In addition to social demographic characteristics, the Davidson Trauma Scale (DTS) and an Earthquake exposure screening scale were administered. RESULTS: PTSD prevalence was 6.53% (69 cases). Logistic regression indicated that intensity of traumatic exposure (odds ratio 6.46, 95% CI 4.47-9.32, p<0.001), not having received psychological counseling (odds ratio 3.28, 95% CI 1.31-8.20, p<0.02) and regular drinking (odds ratio 2.42, 95% CI 1.04-5.62, p<0.05) were significant predictors of PTSD. Being a single-child, not being raised by both parents and regular smoking also independently predicted PTSD if intensity of earthquake traumatic exposure was not included in the model. LIMITATIONS: The self-rated DTS was used to classify PTSD in this study and psychiatric co-morbidity outside of PTSD was not assessed in this sample. CONCLUSION: PTSD is a concern for Military disaster responders; to identify those with high risk of developing PTSD would be important and beneficial.