NSD2 circular RNA promotes metastasis of colorectal cancer by targeting miR‐199b‐5p‐mediated DDR1 and JAG1 signalling

Chen, Liang‐Yan; Zheng, Zhi-Ming; Wang, Lian; Zhao, Yuanyuan; Deng, Min; Liu, Yuhong; Yan, Qin; Tian, Mengmeng; Liu, Yao; Shen, Tong; Sun, Lina; Li, Jianming

doi:10.1002/path.5238

Cited by 73 publications

(66 citation statements)

References 37 publications

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“…DDR1 upregulation has been linked to oncogenic activation, such as KRAS mutations (44), a collagen-dependent amplification loop mechanism, and epigenetic mechanisms. Although all these mechanisms may contribute to DDR1 aberrant expression in CRC, a miRNAdependent epigenetic mechanism was recently documented in this cancer (41,45).…”

Section: Ddr1 In Crc Metastasesmentioning

confidence: 99%

Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer

2020

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Colorectal cancer (CRC) is one of the leading causes of tumor-related death worldwide. While surgery can cure patients with early stage CRC, the 5-year survival rate is only 10% for patients with metastatic disease. Therefore, new anti-metastatic therapies are needed for this cancer. Metastatic spread defines the dissemination of cancer cells with tumor-initiating capacities from the primary tumor and their colonization of distinct organs, mainly the liver, for secondary tumor formation. Although the underlying mechanisms are not fully understood, components of the tumor microenvironment have gained strong interest. Among the known metastatic-promoting factors, collagens are extracellular matrix components that are deposited within the tumor, the tumor microenvironment, and at metastatic site(s), and are recognized to play essential roles during metastasis development. Here, we review recent findings on the metastatic role of the collagen receptors Discoidin Domain Receptors 1 and 2 (DDR1 and DDR2) in CRC and discuss the therapeutic value of targeting these receptor tyrosine kinases in this cancer.

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Section: Ddr1 In Crc Metastasesmentioning

confidence: 99%

Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer

2020

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“…Studies have shown that circPPP1R12A is directly transcribed by PPP1R12A-C peptide participating in YAP signaling transduction [23]. Circ-NSD2 is involved in the occurrence of liver metastasis through the formation of circ-NSD2/miR-199b-5p/DDR1/JAG1 axis [24]. Liver metastasis of colorectal cancer has been regarded as a relatively simple biological event in current studies.…”

Section: Discussionmentioning

confidence: 96%

CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer

Tang

Feng

Huang

et al. 2020

Preprint

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Background Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. Methods The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). The gain- and loss-of-function experiments was conducted in CRC cell lines and animal models. The RNA pull-down, RNA immunoprecipitation n was further employed in exploring the detailed mechanism of circRNA and associated target genes. Results We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly corrected with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. Conclusions The circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.

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“…As is widely recognized, circRNAs could interact with miRNAs to modulate mRNA [32][33][34]. Thus, in this manuscript, we further explored whether circVAPA could exert its role in CRC through regulating the miRNA/mRNA axis.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circVAPA knockdown suppresses colorectal cancer cell growth process by regulating miR-125a/CREB5 axis

Zhang

Yamagata

et al. 2020

Cancer Cell Int

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Background: Colorectal cancer (CRC) is a malignant tumor, and the overall prognosis of patients with advanced CRC is still unsatisfactory. Circular RNAs (circRNAs) vesicle-associated membrane protein-associated protein A (circVAPA) could act as an underlying biomarker in CRC. This study aimed to explore the mechanism of circVAPA in the regulation of CRC growth. Methods: CircVAPA level was measured in CRC tumor tissues. The expression levels of circVAPA, VAPA mRNA, micro-RNA-125a (miR-125a), and cAMP response element binding 5 (CREB5) in CRC cells were detected by RT-qPCR. Cell cycle progression, migration and invasion, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by flow cytometry, transwell assays and Seahorse XF96 Glycolysis Analyzer, severally. The levels of glucose uptake, lactate and ATP production were examined by Glucose Uptake Colorimetric Assay kit, Lactate Assay kit and ATP Colorimetric Assay kit, respectively. The interaction between miR-125a and circVAPA or CREB5 was predicted by Starbase or DIANA TOOL, and verified by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Results: CircVAPA level was up-regulated in CRC tumor tissues. Expression levels of circVAPA and CREB5 were increased, and miR-125a was decreased in CRC cells. CircVAPA knockdown repressed CRC cells cycle progression, migration, invasion and glycolysis. CircVAPA acted as a miR-125a sponge to regulate CREB5 expression. Rescue assay confirmed that miR-125a deletion or CREB5 overexpression weakened the inhibitory effect of circVAPA knockdown on CRC growth. Conclusion: Our studies disclosed that circVAPA knockdown suppressed CRC cells cycle progression, migration, invasion and glycolysis partly by modulating miR-125a/CREB5 axis, suggesting a potential therapeutic strategy for CRC treatment.

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NSD2 circular RNA promotes metastasis of colorectal cancer by targeting miR‐199b‐5p‐mediated DDR1 and JAG1 signalling

Cited by 73 publications

References 37 publications

Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer

Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer

CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer

Circular RNA circVAPA knockdown suppresses colorectal cancer cell growth process by regulating miR-125a/CREB5 axis

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