DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective

Secchi, Massimiliano; Lodola, Camilla; Garbelli, Anna; Bione, Silvia; Maga, Giovanni

doi:10.3390/cancers14153820

Cited by 12 publications

(9 citation statements)

References 172 publications

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“…On the other hand, RBPs can also regulate the expression of lncRNAs at the transcriptional level. DDX3X, one of the members of the DEAD‐box helicase family, is able to control most stages of RNA metabolism from transcription, splicing, RNA export to translation 29,30 . DDX3X can bind to lncRNA TUG1 and increases the stabilization of Bcl‐2‐associated athanogene 5 31 .…”

Section: Discussionmentioning

confidence: 99%

“…DDX3X, one of the members of the DEAD‐box helicase family, is able to control most stages of RNA metabolism from transcription, splicing, RNA export to translation. 29 , 30 DDX3X can bind to lncRNA TUG1 and increases the stabilization of Bcl‐2‐associated athanogene 5. 31 LncRNA Rncr4 (retinal noncoding RNA 4) regulates the inhibitory function of DDX3X to mouse retina architecture.…”

Section: Discussionmentioning

confidence: 99%

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LINC02323 facilitates development of lung squamous cell carcinoma by miRNA sponge and RBP dysregulation and links to poor prognosis

Tsai

Huang

et al. 2022

Thoracic Cancer

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Background The poor outcome of patients with lung squamous cell carcinoma (LUSC) highlights the importance of the identification of novel effective prognostic markers and therapeutic targets. Long noncoding RNAs (lncRNAs) have generally been considered to serve important roles in tumorigenesis and the development of various types of cancer, including LUSC. Methods Here, we aimed to investigate the role of LINC02323 in LUSC and its potential mechanisms by performing comprehensive bioinformatic analyses. Results LINC02323 was elevated and positively associated with unfavorable prognosis of LUSC patients. LINC02323 exerted oncogenic function by competitively binding to miR‐1343‐3p and miR‐6783‐3p, thereby upregulating L1CAM expression. Indeed, we also determined that LINC02323 could interact with the RNA‐binding protein DDX3X, which regulates various stages of RNA expression and processing. Conclusion Taken together, we identified that LINC02323 and its indirect target L1CAM can act as novel biomarkers for determining the prognosis of patients with LUSC and thus deserves further study.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LINC02323 facilitates development of lung squamous cell carcinoma by miRNA sponge and RBP dysregulation and links to poor prognosis

Tsai

Huang

et al. 2022

Thoracic Cancer

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“…The DDX3X gene is one of the most frequently mutated in c-MYC translocated pediatric BL after TP53, ID3 and TCF3 in this study (122)(123)(124)(125), but also in others. While the role and mechanistic consequences of loss-of-function (LOF) mutations in TP53, ID3 and TCF3 have been clarified to a large part, it remains unclear why mutation in the DDX3X gene are selected in BL and the question remains whether this protein is indeed a tumor suppressor or not, or whether it exerts both roles in a context-dependent manner (126).…”

Section: Ddx3x Mutations In Burkitt Lymphoma and Diffuse Large B-cell...mentioning

confidence: 99%

The RNA helicase DDX3 and its role in c-MYC driven germinal center-derived B-cell lymphoma

et al. 2023

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DDX3X is an RNA helicase with many functions in RNA metabolism such as mRNA translation, alternative pre-mRNA splicing and mRNA stability, but also plays a role as a regulator of transcription as well as in the Wnt/beta-catenin- and Nf-κB signaling pathways. The gene encoding DDX3X is located on the X-chromosome, but escapes X-inactivation. Hence females have two active copies and males only one. However, the Y chromosome contains the gene for the male DDX3 homologue, called DDX3Y, which has a very high sequence similarity and functional redundancy with DDX3X, but shows a more restricted protein expression pattern than DDX3X. High throughput sequencing of germinal center (GC)-derived B-cell malignancies such as Burkitt Lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL) samples showed a high frequency of loss-of-function (LOF) mutations in the DDX3X gene revealing several features that distinguish this gene from others. First, DDX3X mutations occur with high frequency particularly in those GC-derived B-cell lymphomas that also show translocations of the c-MYC proto-oncogene, which occurs in almost all BL and a subset of DLBCL. Second, DDX3X LOF mutations occur almost exclusively in males and is very rarely found in females. Third, mutations in the male homologue DDX3Y have never been found in any type of malignancy. Studies with human primary GC B cells from male donors showed that a loss of DDX3X function helps the initial process of B-cell lymphomagenesis by buffering the proteotoxic stress induced by c-MYC activation. However, full lymphomagenesis requires DDX3 activity since an upregulation of DDX3Y expression is invariably found in GC derived B-cell lymphoma with DDX3X LOF mutation. Other studies with male transgenic mice that lack Ddx3x, but constitutively express activated c-Myc transgenes in B cells and are therefore prone to develop B-cell malignancies, also showed upregulation of the DDX3Y protein expression during the process of lymphomagenesis. Since DDX3Y is not expressed in normal human cells, these data suggest that DDX3Y may represent a new cancer cell specific target to develop adjuvant therapies for male patients with BL and DLBCL and LOF mutations in the DDX3X gene.

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“…DDX5 is a multifunctional protein and participates in numerous cellular processes, including mRNA splicing, mRNA export and translation, and ribosome and miRNA bioDDX5sis [5]. The current literature underscores the oncogenic role DDX5 plays in almost all types of cancers, including lung, colon, and breast cancers [6][7][8]. DDX5 plays important roles in maintaining genome stability [9], especially in the context of DNA damage response.…”

Section: Introductionmentioning

confidence: 99%

DDX5 Functions as a Tumor Suppressor in Tongue Cancer

Liu,

Sun,

Long

et al. 2023

Cancers

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DEAD-box polypeptide 5 (DDX5), a DEAD-box RNA helicase, is a multifunctional protein that plays important roles in many physiological and pathological processes. Contrary to its documented oncogenic role in a wide array of cancers, we herein demonstrate that DDX5 serves as a tumor suppressor in tongue cancer. The high expression of DDX5 is correlated with better prognosis for clinical tongue cancer patients. DDX5 downregulates the genes associated with tongue cancer progression. The knockdown of DDX5 promotes, while the overexpression of DDX5 inhibits, tongue cancer proliferation, development, and cisplatin resistance. Furthermore, the expression of DDX5 in tongue cancer is associated with immune cell infiltration in the tumor microenvironment. Specifically, the expression of DDX5 is associated with the reduced infiltration of M2 macrophages and increased infiltration of T cell clusters, which may contribute to anticancer effects in the tumor microenvironment. In this study, we establish DDX5 as a valuable prognostic biomarker and an important tumor suppressor in tongue cancer.

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DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective

Cited by 12 publications

References 172 publications

LINC02323 facilitates development of lung squamous cell carcinoma by miRNA sponge and RBP dysregulation and links to poor prognosis

LINC02323 facilitates development of lung squamous cell carcinoma by miRNA sponge and RBP dysregulation and links to poor prognosis

The RNA helicase DDX3 and its role in c-MYC driven germinal center-derived B-cell lymphoma

DDX5 Functions as a Tumor Suppressor in Tongue Cancer

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