Characterization of NOL7 Gene Point Mutations, Promoter Methylation, and Protein Expression in Cervical Cancer

Doçi, Colleen L.; Mankame, Tanmayi P.; Langerman, Alexander; Ostler, Kelly R.; Kanteti, Rajani; Best, Timothy; Onel, Kenan; Godley, Lucy A.; Salgia, Ravi; Lingen, Mark W.

doi:10.1097/pgp.0b013e318220ba16

Cited by 10 publications

(6 citation statements)

References 49 publications

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“…Increased amounts of SRPK2 can lead to the hyperphosphorylation of serine-arginine-rich proteins, which in turn induces changes in alternative pre-mRNA splicing observed in PD [ 34 ]. NOL7 is a candidate cancer suppressor that localizes to 6p23, a segment with frequent loss of heterozygosity (LOH) in many tumors [ 61 ]. NOL7 interacts with amyloid precursor protein (APP) protein which accumulates in mitochondrial membrane in PD, and that APP interacts with LRRK2 and then is phosphorylated at Thr668 within its intracellular domain to promote neurotoxicity in PD [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease

Wang

Zheng

et al. 2018

BMC Med Genomics

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BackgroundParkinson’s disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation.MethodsWe examine common differentially expressed genes (DEGs) from several PD blood and substantia nigra (SN) microarray datasets by meta-analysis. Further we screen the PD-specific genes from common DEGs using GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs and SNPs associated with the common PD-specific genes, and then identify the mTF-miRNA-gene-gTF network.ResultOur results identified 36 common DEGs in PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were previously known to be associated with PD. Further study of the regulatory miRNAs associated with the common PD-specific genes revealed 14 PD-specific miRNAs in our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide polymorphism (SNP) analysis of the PD-specific genes identified two significant SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified seven significant SNPs. Most of these SNPs are present in the 3′-untranslated region of genes and are controlled by several miRNAs.ConclusionOur study identified a total of 53 common DEGs in PD patients compared with healthy controls in blood and brain datasets and five of these genes were previously linked with PD. Regulatory network analysis identified PD-specific miRNAs, associated long non-coding RNA and feed-forward loops, which contribute to our understanding of the mechanisms underlying PD. The SNPs identified in our study can determine whether a genetic variant is associated with PD. Overall, these findings will help guide our study of the complex molecular mechanism of PD.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0357-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease

Wang

Zheng

et al. 2018

BMC Med Genomics

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Section: Discussionmentioning

confidence: 54%

“…Previous researchers have confirmed that consistent loss of NOL7 through loss of heterozygosity and decreased mRNA and protein expression has been observed in cervical cancer [ 7 ]. Additionally, the experimental study performed by Lingen MW et al also confirmed the suppressive function of NOL7 in cervical cancer [ 7 ]. However, the chromosome region 6p21–23, where NOL7 resides, is frequently amplified in several cancers, including melanoma, and therefore may exert disease-promoting effects in these cancers [ 12 ].…”

Section: Discussionmentioning

confidence: 54%

“…Meanwhile, NOL7 can predict cancer recurrence and survival in cervical cancer patients. Researchers found that tumor-associated mutations and SNP variations harbored in the NOL7 gene potentially contribute to the loss of NOL7 in cancer cells [ 6 , 7 ]. In addition, C-myc and RXRα transcription factors were found to positively regulate NOL7 expression [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Pancancer Analysis of the Oncogenic and Prognostic Role of NOL7: A Potential Target for Carcinogenesis and Survival

Liu

Xie

2022

IJMS

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Despite growing evidence suggesting the critical function of NOL7 in cancer initiation and development, a systematic pancancer analysis of NOL7 is lacking. Herein, we present a comprehensive study of NOL7 which aimed to explore its potential role and detailed mechanisms across 33 human tumors based on The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CATPAC) databases. As a result, both gene and protein levels of NOL7 were found to be increased in various tumor tissues, including breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and head and neck squamous cell carcinoma (HNSC) as compared with corresponding normal tissues. Meanwhile, dysregulated NOL7 expression was found to be closely related to pathological stage and prognosis in several cancers, including LIHC, ovarian serous cystadenocarcinoma (OV), and bladder urothelial carcinoma (BLCA). The DNA methylation level of NOL7 was found to be decreased in most cancers and to be negatively associated with NOL7 expression. Furthermore, NOL7 expression was determined to be significantly associated with levels of infiltrating cells and immune checkpoint genes, including HMGB1. Analysis of NOL7-related genes revealed that RNA metabolism pathways, including “ribosome biogenesis”, “spliceosome”, and “RNA transport”, were mainly involved in the functional mechanism of NOL7 in human cancers. In summary, this pancancer study characterized the relationship between NOL7 expression and clinicopathologic features in multiple cancer types and further showed its potential regulatory network in human cancers. It represents a systemic analysis for further functional and therapeutic studies of NOL7 and highlights its predictive value with respect to the carcinogenesis and prognosis of various cancers, especially LIHC.

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“…To determine the compartment in which NOL7 must reside for its function, we made a series of mutational constructs that targeted NOL7 to the nucleolus (NOL7 wild-type), nucleoplasm (N23(−)) or cytoplasm (N123(−)) (Zhou et al 61 ; Figure 1a). In SiHa cells, which essentially lack endogenous NOL7, 60,62 reintroduction of wild-type nucleolar NOL7 was able to significantly upregulate endogenous TSP-1 expression compared with GFP controls, while cytoplasmic NOL7 had no effect on TSP-1 levels (Figure 1b). However, nucleoplasmic NOL7 was still able to upregulate endogenous TSP-1 to the same levels as wild-type nOl7 (Figure 1b).…”

Section: Resultsmentioning

confidence: 97%

The novel tumor suppressor NOL7 post-transcriptionally regulates thrombospondin-1 expression

2012

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Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis whose expression suppresses tumor growth in vivo. Like many angiogenesis-related genes, TSP-1 expression is tightly controlled by various mechanisms, but there is little data regarding the contribution of post-transcriptional processing to this regulation. NOL7 is a novel tumor suppressor that induces an antiangiogenic phenotype and suppresses tumor growth, in part through upregulation of TSP-1. Here we demonstrate that NOL7 is an mRNA-binding protein that must localize to the nucleoplasm to exert its antiangiogenic and tumor suppressive effects. There, it associates with the RNA-processing machinery and specifically interacts with TSP-1 mRNA through its 3'UTR. Reintroduction of NOL7 into SiHa cells increases luciferase expression through interaction with the TSP-1 3'UTR at both the mRNA and protein levels. NOL7 also increases endogenous TSP-1 mRNA half-life. Further, NOL7 post-transcriptional stabilization is observed in a subset of angiogenesis-related mRNAs, suggesting that the stabilization of TSP-1 may be part of a larger novel mechanism. These data demonstrate that NOL7 significantly alters TSP-1 expression and may be a master regulator that coordinates the post-transcriptional expression of key signaling factors critical for the regulation of the angiogenic phenotype.

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Characterization of NOL7 Gene Point Mutations, Promoter Methylation, and Protein Expression in Cervical Cancer

Cited by 10 publications

References 49 publications

A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease

A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease

Pancancer Analysis of the Oncogenic and Prognostic Role of NOL7: A Potential Target for Carcinogenesis and Survival

The novel tumor suppressor NOL7 post-transcriptionally regulates thrombospondin-1 expression

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