Downregulation of DEAD-box helicase 21 (DDX21) inhibits proliferation, cell cycle, and tumor growth in colorectal cancer via targeting cell division cycle 5-like (CDC5L)

Wang, Kai; Li, Baosong; Peng, Fan; Ren, Xiang; Jiang, Hong

doi:10.1080/21655979.2021.2011636

Cited by 13 publications

(7 citation statements)

References 32 publications

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“…Survival analysis showed that DDX56 was strongly associated with poor prognosis and that DDX56 was overexpressed in most tumor types. 61,62 We then focused on the significance of DDX56 at LIHC and further confirmed the high expression of DDX56 in 2 independent datasets and obtained consistent results at the protein level. Several studies have indicated that DDX56 interacts with the mitotic regulator serine/threonine phosphoprotein phosphatase (PP) 1 and the oncoprotein DEK to regulate tumor progression, and its high expression has been reported in breast and colorectal cancers.…”

supporting

confidence: 54%

Identification and Validation in a Novel Classification of Helicase Patterns for the Prediction of Tumor Proliferation and Prognosis

Yin¹,

Xu²,

Liu³

et al. 2022

JHC

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Background Helicases have been classified as a class of enzymes that determine the stability of the cellular genome. There is growing evidence that helicases can help tumor cells resist drug killing by repairing Deoxyribose Nucleic Acid (DNA) or stabilizing transcription, which may contribute to the understanding of drug resistance. Currently, identifying cancer biomarkers among helicases and stratifying patients according to helicase activity will be able to guide treatment well. Methods We clustered 371 hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas (TCGA) by consensus clustering based on helicase expression profiles to identify potential molecular subtypes. The Multiscale Embedded Gene Co-Expression Network Analysis (MEGENA) algorithm was used to find core differential gene modules between different molecular subtypes, and single-cell analysis was utlized to explore the potential function of hub gene. Immunohistochemical (IHC) staining was used to verify the diagnostic value of DDX56 and its ability to reflect the proliferation efficiency of cancer cells. Results We identified two subtypes associated with helicase. High helicase subtype was associated with poor clinical outcome, massive M0 macrophage infiltration, and highly active cell proliferation features. In addition, we identified a new biomarker, DDX56 , which has not been reported in HCC, was highly expressed in HCC tissues, associated with poor prognosis, and was also shown to be associated with high cell proliferative activity. Conclusion In conclusion, based on helicase expression profiles, we have developed a new classification system for HCC, which is a proliferation-related system, and has clinical significance in evaluating prognosis and treating HCC patients, including immunotherapy and chemotherapy. In addition, we identified a new biomarker, DDX 56 , which is overexpressed in HCC tissues, predicts a poor prognosis and is a validated index of tumor cell proliferation.

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supporting

confidence: 54%

Identification and Validation in a Novel Classification of Helicase Patterns for the Prediction of Tumor Proliferation and Prognosis

Yin¹,

Xu²,

Liu³

et al. 2022

JHC

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“…1K , S1K, L ). Previous results showed that loss of DDX21 expression suppressed the CRC cell proliferation, cell cycle and tumor growth [ 29 , 30 ], suggesting that DDX21 may play an important role in the tumorigenesis of CRC. We also validated the pro-proliferation effect of DDX21 in CRC (Fig.…”

Section: Resultsmentioning

confidence: 99%

Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway

et al. 2023

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RNA binding proteins (RBPs) contributes to cancer progression, but the underlying mechanism reminds unclear. Here, we find that DDX21, a representative RBP, is highly expressed in colorectal cancer (CRC), which leads to CRC cell migration and invasion in vitro, and CRC to liver metastasis and lung metastasis in vivo. This effect of DDX21 on CRC metastasis is correlated to the activation of Epithelial-mesenchymal transition (EMT) pathway. Moreover, we reveal that DDX21 protein is phase separated in vitro and in CRC cells, which controls CRC metastasis. Phase-separated DDX21 highly binds on MCM5 gene locus, which is markedly reduced when phase separation is disrupted by mutations on its intrinsically disordered region (IDR). The impaired metastatic ability of CRC upon DDX21 loss is restored by ectopic expression of MCM5, indicating MCM5 is a key downstream target of DDX21 for CRC metastasis. Furthermore, co-higher expressions of DDX21 and MCM5 is significantly correlated with poor survival outcomes of stage III and IV CRC patients, indicating the importance of this mechanism in CRC late and metastatic stage. Altogether, our results elucidate a new model of DDX21 in regulating CRC metastasis via phase separation.

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“…DDX21 was highly expressed in human CRC (37)(38)(39)(132)(133)(134). Its expression was associated with CRC cancer stages (133).…”

Section: Ddx21mentioning

confidence: 99%

Role and therapeutic potential of DEAD-box RNA helicase family in colorectal cancer

Zheng,

Chen,

Ling

et al. 2023

Front. Oncol.

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Colorectal cancer (CRC) is the third most commonly diagnosed and the second cancer-related death worldwide, leading to more than 0.9 million deaths every year. Unfortunately, this disease is changing rapidly to a younger age, and in a more advanced stage when diagnosed. The DEAD-box RNA helicase proteins are the largest family of RNA helicases so far. They regulate almost every aspect of RNA physiological processes, including RNA transcription, editing, splicing and transport. Aberrant expression and critical roles of the DEAD-box RNA helicase proteins have been found in CRC. In this review, we first summarize the protein structure, cellular distribution, and diverse biological functions of DEAD-box RNA helicases. Then, we discuss the distinct roles of DEAD-box RNA helicase family in CRC and describe the cellular mechanism of actions based on recent studies, with an aim to provide future strategies for the treatment of CRC.

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Downregulation of DEAD-box helicase 21 (DDX21) inhibits proliferation, cell cycle, and tumor growth in colorectal cancer via targeting cell division cycle 5-like (CDC5L)

Cited by 13 publications

References 32 publications

Identification and Validation in a Novel Classification of Helicase Patterns for the Prediction of Tumor Proliferation and Prognosis

Identification and Validation in a Novel Classification of Helicase Patterns for the Prediction of Tumor Proliferation and Prognosis

Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway

Role and therapeutic potential of DEAD-box RNA helicase family in colorectal cancer

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