Neuralized-2: Expression in human and rodents and interaction with Delta-like ligands

Rullinkov, Grete; Tamme, Richard; Sarapuu, Anzelika; Laurén, Juha; Sepp, Mari; Palm, Kaia; Timmusk, Tõnis

doi:10.1016/j.bbrc.2009.08.147

Cited by 13 publications

(25 citation statements)

References 28 publications

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“…There are 3 crucial domains in the NEURL1B protein, including the RING Zn-finger (RZD) domain and two Neuralized Homology Repeat (NHR) domains [ 26 ]. It was confirmed that NEURL1B was mainly localized in cytoplasm and peak expression was focusd in embryogenesis [ 26 ]. In our present study, a new characteristic of tumor suppressor gene for NEURL1B was shown in CC.…”

Section: Discussionmentioning

confidence: 99%

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Liu

Zhang

et al. 2020

Cancer Cell Int

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Background Aberrant methylation and miRNA-target-gene regulation function as important mechanisms for gene inactivation in colon carcinogenesis. Although a serious of molecular events (such as aberrant alterations of genomics and epigenetics) have been identified to be related to prognostic in colon cancer (CC) patients, beneficial biomarkers for early diagnosis and prognostic evaluation remain largely unknown. Methods In our study, the role of NEURL1B, including gene expression analysis, methylation characteristic, miRNA-target regulation, diagnostic and prognostic significance, were evaculated using multiple bioinformatic tools based on TCGA database and clinical samples. Results Our data showed that NEURL1B was aberrantly downregulated in CC, regardless of the mRNA level or protein level. Moreover, ROC curve and multivariate Cox regression analysis demonstrated that NEURL1B was a diagnostic and independent prognostic facter for CC patients. Of interest, methylation of NEURL1B was also high and closely associated with poor survival in CC. In addition, multiple NEURL1B-target miRNAs were found to be overexpressed in CC tissues. Thus, our findings suggested that NEURL1B participated in the pathological processes of CC as a tumor suppressor gene. Double management, including DNA methylation modification and miRNA-target regulation, were considered to be related to the downregulation of NEURL1B. Importantly, there existing be an significant intersection between miRNAs-target pathways and NEURL1B-target pathways, suggesting that miR-17 and miR-27a might promote tumor cell malignant property by targeting NEURL1B degradation via the activation of PI3K/AKT signaling pathway. Conclusions Taking together, the first investigation of NEURL1B in CC provide us a strong evidences that it might be served as a potential biomarkers for early diagnosis and prognostic evaluation in CC.

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Section: Discussionmentioning

confidence: 99%

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Liu

Zhang

et al. 2020

Cancer Cell Int

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“…Several putative genes reported to be involved in tumorigenesis of various cancers were demonstrated in our study. For example, Neuralized-1B is the E3 ubiquitin ligase that is required for endocytosis regulating both the receptor and ligand side in Notch signaling (37,38). Relatively frequent deregulation of the Notch pathway and Notch ligand Jagged2/miR-200-dependent pathway in NSCLC indicates the significance and mechanisms underpinning Notch pathway activation in lung cancer (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Genomic copy number alterations associated with the early brain metastasis of non-small cell lung cancer

Lee

Seol

Choi

et al. 2012

International Journal of Oncology

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Frequent early development of systemic metastasis leads to unfavourable clinical prognosis of non-small cell lung cancer (NSCLC). Although brain metastasis (BM) contributes significantly to morbidity and mortality of NSCLC, relevant driver mechanisms are largely unknown. To elucidate genetic alterations associated with early BM of NSCLC, we retrospectively collected 18 NSCLC cases with BM [12 adenocarcinomas (ADC) and 6 squamous cell carcinomas (SQCC)] whose surgical tissues of both primary and brain metastatic tumors were preserved as formaldehyde-fixed and paraffin-embedded (FFPE) pathological samples. When chromosomal copy number alterations (CNA) of those FFPE samples were analysed by the Molecular Inversion Probe (MIP) technology, the most frequent CNAs detected in primary lung ADCs were gains of 3q, 5p, 5q, 6p, 8q, 9p, 11p, 15q, 17q and losses of 10q and 22q whereas primary lung SQCCs revealed gains in 4q and 12q and loss in 9q. In particular, when comparative MIP was performed in primary 12 ADCs depending on the pattern of BM to uncover predetermining signatures that can predict the risk of BM, selectively amplified regions of primary lung ADCs (5q35, 10q23 and 17q23-24) were identified as significantly associated with the development of early BM within 3 months after first diagnosis of primary tumors. Those regions harbour several candidate genes including NeurL1B, ACTA2, FAS and ICAM2. Although more validation is needed, the genetic signatures elucidated in this study help to identify useful molecular markers deﬁning an NSCLC patient subgroup at risk of early BM, guiding therapeutic decisions.

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“…Using the DAVID functional annotation clustering tool, the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO), we predicted the genes linked to ubiquitin-mediated proteolysis as the miR-221-5p targets (Supplemental Figure 13A). Neurl1a and Neurl1b, 2 adaptor components of the E3 ubiquitin ligase complex (29)(30)(31), were thereby identified as potential targets ( Figure 6A). Human HEK293 cells that expressed luciferase constructs containing Neurl1a and Neurl1b 3′-UTR-binding sites were used to determine the role of miR-221-5p in Neurl1a and Neurl1b expression.…”

Section: Resultsmentioning

confidence: 99%

CB1 agonism prolongs therapeutic window for hormone replacement in ovariectomized mice

Kun¹,

Yang²,

Yang³

et al. 2019

Journal of Clinical Investigation

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Neuralized-2: Expression in human and rodents and interaction with Delta-like ligands

Cited by 13 publications

References 28 publications

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Genomic copy number alterations associated with the early brain metastasis of non-small cell lung cancer

CB1 agonism prolongs therapeutic window for hormone replacement in ovariectomized mice

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