Long non-coding RNA ZFAS1 promotes colorectal cancer tumorigenesis and development through DDX21-POLR1B regulatory axis

Wang, Xiufang; Wu, Zhuona; Qin, Wenyan; Lu, Senxu; Li, Yalun; Wang, Yuanhe; Hu, Xiaoyun; Xu, Dong-ping; Wu, Yutong; Chen, Qiuchen; Yao, Weifan; Liu, Mingyan; Wu, Huizhe

doi:10.18632/aging.103875

Cited by 27 publications

(13 citation statements)

References 27 publications

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“…The current investigation found that DDX21 was dramatically overexpressed in certain CRC cells, but the role and special mechanism of DDX21 in CRC are not reported yet [ 28 ]. Thus, we firstly assessed the role of DDX21 both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

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

Peng

et al. 2021

Bioengineered

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Identification of novel anti-tumor target is crucial for cancer diagnosis, prognosis, and therapeutic strategy. The study aimed to explore the roles and interaction of DEAD-box helicase 21 (DDX21) and cell division cycle 5-like (CDC5L) in colorectal cancer (CRC) progression. Levels of DDX21 and CDC5L were detected in colorectal cancer cell lines by RT-qPCR and Western blot assay. The role of DDX21 and CDC5L on the cell proliferation, cell cycle and tumor growth were evaluated both in vitro and in vivo . The interaction of DDX21 and CDC5L was predicted by The STRING publicly available data and verified by immunoprecipitation. The results showed that DDX21 was dramatically upregulated in colorectal cancer cells. In vivo and in vitro experiments revealed that downregulation of DDX21 suppressed colorectal cancer cell proliferation, colony formation, cell cycle development, and tumor growth, while overexpression of CDC5L reversed the suppressive effects of DDX21 silencing. Furthermore, DDX21 interacted with CDC5L to exert the tumor-promoting effects in CRC. In summary, the data indicate a novel role for DDX21/CDC5L in the development of CRC, which enrich the therapeutic strategy for CRC.

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Section: Discussionmentioning

confidence: 99%

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

Peng

et al. 2021

Bioengineered

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“…DDX21 is a transcriptional activator of c-Jun via their direct interaction to regulate mRNA expression of the downstream target genes, including EGFR and cyclin D1 [ 65 ]. DDX21 is dysregulated in colon cancer, lymphomas, neuroblastoma, and some breast cancers ( Table 1 ) [ 17 , 66 , 67 , 68 ]. Upregulation of DDX21 promotes breast cancer cell proliferation by activation of the transcription factor AP-1 to regulate the transcription of cyclin D1 and rRNA processing, resulting in the increase of cells in the S phase ( Figure 3 ) [ 65 , 69 ].…”

Section: The Role Of Rna Helicases In Regulation Of Cell Cycle Progressionmentioning

confidence: 99%

DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

Zhang

2021

Cells

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Cell cycle is regulated through numerous signaling pathways that determine whether cells will proliferate, remain quiescent, arrest, or undergo apoptosis. Abnormal cell cycle regulation has been linked to many diseases. Thus, there is an urgent need to understand the diverse molecular mechanisms of how the cell cycle is controlled. RNA helicases constitute a large family of proteins with functions in all aspects of RNA metabolism, including unwinding or annealing of RNA molecules to regulate pre-mRNA, rRNA and miRNA processing, clamping protein complexes on RNA, or remodeling ribonucleoprotein complexes, to regulate gene expression. RNA helicases also regulate the activity of specific proteins through direct interaction. Abnormal expression of RNA helicases has been associated with different diseases, including cancer, neurological disorders, aging, and autosomal dominant polycystic kidney disease (ADPKD) via regulation of a diverse range of cellular processes such as cell proliferation, cell cycle arrest, and apoptosis. Recent studies showed that RNA helicases participate in the regulation of the cell cycle progression at each cell cycle phase, including G1-S transition, S phase, G2-M transition, mitosis, and cytokinesis. In this review, we discuss the essential roles and mechanisms of RNA helicases in the regulation of the cell cycle at different phases. For that, RNA helicases provide a rich source of targets for the development of therapeutic or prophylactic drugs. We also discuss the different targeting strategies against RNA helicases, the different types of compounds explored, the proposed inhibitory mechanisms of the compounds on specific RNA helicases, and the therapeutic potential of these compounds in the treatment of various disorders.

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“…The ZFAS1/DDX21/POLR1B signaling regulation axis may also be a new biomarker for targeted CRC treatment, where ZFAS1 knockdown dramatically reduced cancer cell properties and increase apoptosis. This inhibitory effect could be reversed by DDX21 overexpression 39 . Expanding future studies to include the effects of snoRNAs in CRC is also relevant.…”

Section: Discussionmentioning

confidence: 95%

Integrated whole transcriptome and small RNA analysis revealed multiple regulatory networks in colorectal cancer

Shaath

Toor

Nada

et al. 2021

Sci Rep

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Colorectal cancer (CRC) remains a global disease burden and a leading cause of cancer related deaths worldwide. The identification of aberrantly expressed messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), and the resulting molecular interactions and signaling networks is essential for better understanding of CRC, identification of novel diagnostic biomarkers and potential development of therapeutic interventions. Herein, we performed microRNA (miRNA) sequencing on fifteen CRC and their non-tumor adjacent tissues and whole transcriptome RNA-Seq on six paired samples from the same cohort and identified alterations in miRNA, mRNA, and lncRNA expression. Computational analyses using Ingenuity Pathway Analysis (IPA) identified multiple activated signaling networks in CRC, including ERBB2, RABL6, FOXM1, and NFKB networks, while functional annotation highlighted activation of cell proliferation and migration as the hallmark of CRC. IPA in combination with in silico prediction algorithms and experimentally validated databases gave insight into the complex associations and interactions between downregulated miRNAs and upregulated mRNAs in CRC and vice versa. Additionally, potential interaction between differentially expressed lncRNAs such as H19, SNHG5, and GATA2-AS1 with multiple miRNAs has been revealed. Taken together, our data provides thorough analysis of dysregulated protein-coding and non-coding RNAs in CRC highlighting numerous associations and regulatory networks thus providing better understanding of CRC.

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Long non-coding RNA ZFAS1 promotes colorectal cancer tumorigenesis and development through DDX21-POLR1B regulatory axis

Cited by 27 publications

References 27 publications

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)

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)

DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

Integrated whole transcriptome and small RNA analysis revealed multiple regulatory networks in colorectal cancer

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