RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression

Shan, Hong; Liu, Tianze; Gan, Hairun; He, Simeng; Deng, Jia; Hu, Xinyan; Li, Luting; Cai, Li; He, Jianzhong; Long, Haoyu; Cai, Jianxun; Li, Hanjie; Zhang, Qianqian; Wang, Lijie; Chen, Fangbin; Chen, Yuming; Zhang, Haopei; Li, Jian; Yang, Lukun; Liu, Ye; Yang, Jianhua; Kuang, Dong-Ming; Pang, Pengfei; He, Huanhuan

doi:10.1158/0008-5472.can-21-3748

Cited by 13 publications

(8 citation statements)

References 43 publications

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“…To identify the region of binding on FANCA mRNA, we used the RSAT (Regulatory Sequence Analysis Tools) website tool (http://rsat.sb-roscoff.fr/matrix-scan.cgi) to scan FANCA mRNA sequence with the motif we reported previously. 29 We identified 6 putative binding sites and constructed 5 corresponding probes for RNA pull-down assay (Figure 5F). The results revealed that the region 1721 to 2845 nucleotide (including site 3) in FANCA mRNA was critical for DDX24 binding (Figure 5G).…”

Section: Resultsmentioning

confidence: 99%

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

Gong

Liang

Liu

et al. 2023

ATVB

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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: CMC/VSMC-specific Ddx24 knockout mice were generated by crossing Tagln -Cre mice with Ddx24 flox/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 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.

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Section: Resultsmentioning

confidence: 99%

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

Gong

Liang

Liu

et al. 2023

ATVB

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“…It is known that among the DEAD-box RNA helicases, DDX6 is involved in a wide range of RNA life processes: translation inhibition, mRNA degradation, transport and storage, translation activation, and nuclear export [ 45 ]. For DDX24, a correlation has been shown between its elevated levels in hepatocellular carcinoma tissues and poor prognosis of this disease [ 47 ]. Interestingly, DDX24 is necessary for the organization of muscle fibers and specification of the anterior pole, which is important for regenerating the head in planarians [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

Insights into the Cellular Localization and Functional Properties of TSPYL5 Protein

Silonov,

Smirnov,

Shmidt

et al. 2023

IJMS

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In recent years, the role of liquid–liquid phase separation (LLPS) and intrinsically disordered proteins (IDPs) in cellular molecular processes has received increasing attention from researchers. One such intrinsically disordered protein is TSPYL5, considered both as a marker and a potential therapeutic target for various oncological diseases. However, the role of TSPYL5 in intracellular processes remains unknown, and there is no clarity even in its intracellular localization. In this study, we characterized the intracellular localization and exchange dynamics with intracellular contents of TSPYL5 and its parts, utilizing TSPYL5 fusion proteins with EGFP. Our findings reveal that TSPYL5 can be localized in both the cytoplasm and nucleoplasm, including the nucleolus. The nuclear (nucleolar) localization of TSPYL5 is mediated by the nuclear/nucleolar localization sequences (NLS/NoLS) identified in the N-terminal intrinsically disordered region (4–27 aa), while its cytoplasmic localization is regulated by the ordered NAP-like domain (198–382 aa). Furthermore, our results underscore the significant role of the TSPYL5 N-terminal disordered region (1–198 aa) in the exchange dynamics with the nucleoplasm and its potential ability for phase separation. Bioinformatics analysis of the TSPYL5 interactome indicates its potential function as a histone and ribosomal protein chaperone. Taken together, these findings suggest a significant contribution of liquid–liquid phase separation to the processes involving TSPYL5, providing new insights into the role of this protein in the cell’s molecular life.

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“…In HCC, ADAM9 is known to be overexpressed and is responsible for inducing ROS generation, which in turn promotes HCC cell invasion ( 34 ). Additionally, LAMB1 has been shown to be regulated by the RNA helicase DDX24, which contributes to the malignant progression of HCC ( 35 ). However, the role of SPON2 in HCC is still a matter of debate.…”

Section: Discussionmentioning

confidence: 99%

Combining WGCNA and machine learning to construct basement membrane-related gene index helps to predict the prognosis and tumor microenvironment of HCC patients and verifies the carcinogenesis of key gene CTSA

Sun

Wang

et al. 2023

Front. Immunol.

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Hepatocellular carcinoma (HCC) is a malignant tumor with high recurrence and metastasis rates and poor prognosis. Basement membrane is a ubiquitous extracellular matrix and is a key physical factor in cancer metastasis. Therefore, basement membrane-related genes may be new targets for the diagnosis and treatment of HCC. We systematically analyzed the expression pattern and prognostic value of basement membrane-related genes in HCC using the TCGA-HCC dataset, and constructed a new BMRGI based on WGCNA and machine learning. We used the HCC single-cell RNA-sequencing data in GSE146115 to describe the single-cell map of HCC, analyzed the interaction between different cell types, and explored the expression of model genes in different cell types. BMRGI can accurately predict the prognosis of HCC patients and was validated in the ICGC cohort. In addition, we also explored the underlying molecular mechanisms and tumor immune infiltration in different BMRGI subgroups, and confirmed the differences in response to immunotherapy in different BMRGI subgroups based on the TIDE algorithm. Then, we assessed the sensitivity of HCC patients to common drugs. In conclusion, our study provides a theoretical basis for the selection of immunotherapy and sensitive drugs in HCC patients. Finally, we also considered CTSA as the most critical basement membrane-related gene affecting HCC progression. In vitro experiments showed that the proliferation, migration and invasion abilities of HCC cells were significantly impaired when CTSA was knocked down.

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RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression

Cited by 13 publications

References 43 publications

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

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

Insights into the Cellular Localization and Functional Properties of TSPYL5 Protein

Combining WGCNA and machine learning to construct basement membrane-related gene index helps to predict the prognosis and tumor microenvironment of HCC patients and verifies the carcinogenesis of key gene CTSA

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