Copy number variation, increased gene expression, and molecular mechanisms of neurofascin in lung cancer

Erdem, Johanna Samulin; Arnoldussen, Yke Jildouw; Skaug, Vidar; Haugen, Aage; Zienolddiny, Shanbeh

doi:10.1002/mc.22664

Cited by 19 publications

(10 citation statements)

References 35 publications

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“…Overexpression of NAFSC could partially counteracted the inhibitory effect of miR-3650 in HCC metastasis and EMT. Actually, Samulin Erdem et al showed that knockdown of NFASC could decrease the migration of non-small cell lung cancer cells, rearrange the actin cytoskeleton and inhibit F-actin networks [27], which was consistent with our current results. This implying that miR-3650 inhibit the migration and EMT abilities of HCC cells at least in part by directly binding and inhibiting NFASC expression (Fig.…”

Section: Discussionsupporting

confidence: 92%

Tumor-suppressive miR-3650 inhibits tumor metastasis by directly targeting NFASC in hepatocellular carcinoma

Huang

et al. 2019

Aging

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In recent years, a growing body of evidence has provided support for the important role of microRNAs (miRNAs) in the progression of human cancers. A recent study showed that a novel miRNA miR-3650 expression was significantly decreased in hepatocellular carcinoma (HCC). However, the precise role of miR-3650 in HCC have remained poorly understood. In this study, we found that miR-3650 expression was frequently decreased in HCC tissues. Low expression of miR-3650 is positively associated with tumor metastasis and poor survival of HCC patients. Forced expression of miR-3650 significantly inhibited the migration and epithelial-mesenchymal transition (EMT) of HCC cells. Through bioinformatic analysis and luciferase assays, we confirmed that neurofascin (NFASC) is a directly target mRNA of miR-3650. Rescue experiment demonstrated that NAFSC overexpression could partially counteracted the inhibitory effect of miR-3650 in HCC metastasis and EMT. In conclusion, our findings are the first time to demonstrate that reduced expression of miR-3650 in HCC was correlated with tumor metastasis and poor survival. MiR-3650 repressed HCC migration and EMT by directly targeting NFASC. Our findings suggested that miR-3650 may serve as a potential prognostic marker and promising application in HCC therapy.

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Section: Discussionsupporting

confidence: 92%

Tumor-suppressive miR-3650 inhibits tumor metastasis by directly targeting NFASC in hepatocellular carcinoma

Huang

et al. 2019

Aging

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“…Publicly available databases like TCGA, METABRIC, or GEO, which are common in the cancer research community, help better understand tumor heterogeneity, detect biomarker genes, and define hidden molecular mechanisms in multi-omics research (Xia Q. et al, 2019). Moreover, lines of previous evidence indicate notable relationships between CNA and mRNA, such as there is a high association of CNA with the development and progression of cancers by regulating gene expression level (Huang et al, 2017;Samulin Erdem et al, 2017;Zhou et al, 2017;Gut et al, 2018), as well as the similar regulatory associations between MET and mRNA (Herman and Baylin, 2003;Shen and Laird, 2013). Even a poor grasp of the additional biological complexity of breast tumors neglected at the expression level can be revealed at the DNA methylation level, possibly resulting in finer subgroups with clinical meaning (Rønneberg et al, 2011).…”

Section: Conclusion and Discussionmentioning

confidence: 99%

Multi-Omics Analysis Detects Novel Prognostic Subgroups of Breast Cancer

Nguyen¹,

Nguyen

et al. 2020

Front. Genet.

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The unprecedented proliferation of recent large-scale and multi-omics databases of cancers has given us many new insights into genomic and epigenomic deregulation in cancer discovery in general. However, we wonder whether or not there exists a systematic connection between copy number aberrations (CNA) and methylation (MET)? If so, what is the role of this connection in breast cancer (BRCA) tumorigenesis and progression? At the same time, the PAM50 intrinsic subtypes of BRCA have gained the most attention from BRCA experts. However, this classification system manifests its weaknesses including low accuracy as well as a possible lack of association with biological phenotypes, and even further investigations on their clinical utility were still needed. In this study, we performed an integrative analysis of three-omics profiles, CNA, MET, and mRNA expression, in two BRCA patient cohorts (one for discovery and another for validation)-to elucidate those complicated relationships. To this purpose, we first established a set of CNAcor and METcor genes, which had CNA and MET levels significantly correlated (and anti-correlated) with their corresponding expression levels, respectively. Next, to revisit the current classification of BRCA, we performed single and integrated clustering analyses using our clustering method PINSPlus. We then discovered two biologically distinct subgroups that could be an improved and refined classification system for breast cancer patients, which can be validated by a third-party data. Further studies were then performed and realized each-subgroup-specific genes and different interactions between each of the two identified subgroups with the age factor. These findings can show promise as diagnostic and prognostic values in BRCA, and a potential alternative to the PAM50 intrinsic subtypes in the future.

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“…It is generally accepted that somatic CNV is highly associated with the development and progression of numerous cancers by impacting gene expression level [9–19]. Samulin Erdem et al [13] found that Neurofascin (NFASC) gene is significantly amplified and overexpressed in non-small cell lung cancer (NSCLC) patients and the novel role of NFASC is identified in the regulation of cell motility and NSCLC migration. Dong et al [16] analyzed the copy number alterations and differentially transcribed genes in esophageal cancer and observed a noteworthy association between CNV and differential gene expression for FAM60A, TFDP1, CDC25B and MCM2.…”

Section: Introductionmentioning

confidence: 99%

Copy number variation is highly correlated with differential gene expression: a pan-cancer study

et al. 2019

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BackgroundCancer is a heterogeneous disease with many genetic variations. Lines of evidence have shown copy number variations (CNVs) of certain genes are involved in development and progression of many cancers through the alterations of their gene expression levels on individual or several cancer types. However, it is not quite clear whether the correlation will be a general phenomenon across multiple cancer types.MethodsIn this study we applied a bioinformatics approach integrating CNV and differential gene expression mathematically across 1025 cell lines and 9159 patient samples to detect their potential relationship.ResultsOur results showed there is a close correlation between CNV and differential gene expression and the copy number displayed a positive linear influence on gene expression for the majority of genes, indicating that genetic variation generated a direct effect on gene transcriptional level. Another independent dataset is utilized to revalidate the relationship between copy number and expression level. Further analysis show genes with general positive linear influence on gene expression are clustered in certain disease-related pathways, which suggests the involvement of CNV in pathophysiology of diseases.ConclusionsThis study shows the close correlation between CNV and differential gene expression revealing the qualitative relationship between genetic variation and its downstream effect, especially for oncogenes and tumor suppressor genes. It is of a critical importance to elucidate the relationship between copy number variation and gene expression for prevention, diagnosis and treatment of cancer.

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Copy number variation, increased gene expression, and molecular mechanisms of neurofascin in lung cancer

Cited by 19 publications

References 35 publications

Tumor-suppressive miR-3650 inhibits tumor metastasis by directly targeting NFASC in hepatocellular carcinoma

Tumor-suppressive miR-3650 inhibits tumor metastasis by directly targeting NFASC in hepatocellular carcinoma

Multi-Omics Analysis Detects Novel Prognostic Subgroups of Breast Cancer

Copy number variation is highly correlated with differential gene expression: a pan-cancer study

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