CNVs Associated with Susceptibility to Cancers: A Mini-Review

Furuya, Tomoko; Suehiro, Yutaka; Namiki, Yukihisa; Sasaki, Kohsuke

doi:10.4236/jct.2015.65044

Cited by 7 publications

(8 citation statements)

References 73 publications

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“…We controlled for population stratification, applied filters which are stringent for CNV studies, and utilized 2 different CNV calling algorithms to ensure comprehensive detection of CNVs. Some of the reported CNV regions in this study were indeed characterized as disease conferring across a spectrum of phenotypes and therefore provide confidence in our study findings [Butler et al, 2005;Bailey et al, 2008;Diskin et al, 2009;Glessner et al, 2009Glessner et al, , 2010Ehli et al, 2012;Stadler et al, 2012;Lalani et al, 2013;Nagamani et al, 2013;Ukkola-Vuoti et al, 2013;Chettier et al, 2014;Szatkiewicz et al, 2014;Furuya et al, 2015].…”

supporting

confidence: 59%

A Genome-Wide Association Study to Identify Potential Germline Copy Number Variants for Sporadic Breast Cancer Susceptibility

Sapkota

Narasimhan

Kumaran

et al. 2016

Cytogenet Genome Res

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Breast cancer (BC) predisposition in populations arises from both genetic and nongenetic risk factors. Structural variations such as copy number variations (CNVs) are heritable determinants for disease susceptibility. The primary objectives of this study are (1) to identify CNVs associated with sporadic BC using a genome-wide association study (GWAS) design; (2) to utilize 2 distinct CNV calling algorithms to identify concordant CNVs as a strategy to reduce false positive associations in the hypothesis-generating GWAS discovery phase, and (3) to identify potential candidate CNVs for follow-up replication studies. We used Affymetrix SNP Array 6.0 data profiled on Caucasian subjects (422 cases/348 controls) to call CNVs using algorithms implemented in Nexus Copy Number and Partek Genomics Suite software. Nexus algorithm identified CNVs associated with BC (731 autosomal CNVs with >5% frequency in the total sample and Q < 0.05). Thirteen CNVs were identified when Partek algorithm-called CNVs were overlapped with Nexus-identified CNVs; these CNVs showed concordances for frequency, effect size, and direction. Coding genes present within BC-associated CNVs were known to play a role in disease etiology and prognosis. Long noncoding RNAs identified within CNVs showed tissue-specific expression, indicating potential functional relevance of the findings. The identified candidate CNVs warrant independent replication.

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supporting

confidence: 59%

A Genome-Wide Association Study to Identify Potential Germline Copy Number Variants for Sporadic Breast Cancer Susceptibility

Sapkota

Narasimhan

Kumaran

et al. 2016

Cytogenet Genome Res

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“…Genomic and molecular-phenotypic heterogeneity due to CNV is thought to influence HCC development and progression. 7 Many examples of CNV have been identified in intergenic regions of DNA in human HCC cells. 19,20,25 In this study, based on WGS and bioinformatics analyses of 49 matched HCC samples and para-cancer tissues, the genomic CNV of lncRNAs in Chinese patients with early HCC recurrence after curative resection was revealed for the first time.…”

Section: Discussionmentioning

confidence: 99%

“…CNV plays critical roles in cancer development and progression by activating oncogenes and inactivating tumor suppressors. 7 Protein-coding genes only account for 2% of the human genome, and numerous CNVs in noncoding genomic regions appear at a high frequency in populations. 8 Long noncoding RNAs (lncRNAs) are transcribed RNA sequences at least 200 nucleotides in length that do not encode any protein.…”

Section: Introductionmentioning

confidence: 99%

LINC01133 promotes hepatocellular carcinoma progression by sponging miR‐199a‐5p and activating annexin A2

Yin

Luo

et al. 2021

Clinical & Translational Med

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Background Long noncoding RNAs (lncRNAs) are functionally associated with cancer development and progression. Although gene copy number variation (CNV) is common in hepatocellular carcinoma (HCC), it is not known how CNV in lncRNAs affects HCC progression and recurrence. We aimed to identify a CNV‐related lncRNA involved in HCC progression and recurrence and illustrate its underlying mechanisms and prognostic value. Methods We analyzed the whole genome sequencing (WGS) data of matched cancerous and noncancerous liver samples from 49 patients with HCC to identify lncRNAs with CNV. The results were validated in another cohort of 238 paired HCC and nontumor samples by TaqMan copy number assay. We preformed Kaplan‐Meier analysis and log‐rank test to identify lncRNA CNV with prognostic value. We conducted loss‐ and gain‐of‐function studies to explore the biological functions of LINC01133 in vitro and in vivo. The competing endogenous RNAs (ceRNAs) mechanism was clarified by microRNA sequencing (miR‐seq), quantitative real‐time PCR (qRT‐PCR), western blot, and dual‐luciferase reporter assays. We confirmed the binding mechanism between lncRNA and protein by RNA pull‐down, RNA immunoprecipitation, qRT‐PCR, and western blot analyses. Results Genomic copy numbers of LINC01133 were increased in HCC, which were positively related with the elevated expression of LINC01133. Increased copy number of LINC01133 predicted the poor prognosis in HCC patients. LINC01133 overexpression in HCC cells promoted proliferation and aggressive phenotypes in vitro, and facilitated tumor growth and lung metastasis in vivo, whereas LINC01133 knockdown had the opposite effects. LINC01133 sponged miR‐199a‐5p, resulting in enhanced expression of SNAI1, which induced epithelial‐to‐mesenchymal transition (EMT) in HCC cells. In addition, LINC01133 interacted with Annexin A2 (ANXA2) to activate the ANXA2/STAT3 signaling pathway. Conclusions LINC01133 promotes HCC progression by sponging miR‐199a‐5p and interacting with ANXA2. LINC01133 CNV gain is predictive of poor prognosis in patients with HCC.

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“…Genomic and molecular phenotype heterogeneity due to CNV is thought to in uence HCC development and progression [21]. Many CNVs have been identi ed in intergenic regions of DNA in human HCC cells [22].…”

Section: Discussionmentioning

confidence: 99%

The Long Non-coding RNA LINC01133 Promotes Hepatocellular Carcinoma Progression by Sponging miR-199a-5p and Activating Annexin A2

Yin

Luo

et al. 2020

Preprint

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Background: Long non-coding RNAs (lncRNAs) have been found to be functionally associated with cancer development and progression. Although copy number variations (CNVs) are common in hepatocellular carcinoma (HCC), little is known about how CNVs in lncRNAs affect HCC progression and recurrence.Methods: We analyzed the whole genome sequencing (WGS) data of matched cancerous and non-cancerous liver samples from 49 patients with HCC to identify lncRNAs with CNVs. The results were validated in another cohort of 238 paired HCC and non-tumor samples by TaqMan copy number assay. Kaplan-Meier analysis and the log-rank test were performed to determine the prognostic value of CNVs in lincRNAs. Loss- and gain-of-function studies were conducted to determine the biological functions of LINC01133 in vitro and in vivo. The competing endogenous RNAs (ceRNAs) mechanism was clarified by microRNA sequencing (miR-seq), quantitative real-time PCR (qRT-PCR), western blot, and dual-luciferase reporter analyses. The protein binding mechanism was confirmed by RNA pull-down, RNA immunoprecipitation (RIP), qRT-PCR, and western blot analyses.Results: Genomic copy number of LINC01133 was increased in HCC, which is positively related with the elevated expression of LINC01133. Increased copy number of LINC01133 predicted the poor prognosis in HCC patients. LINC01133 overexpression promoted proliferation, colony formation, migration, and invasion in vitro, and facilitated tumor growth and lung metastasis in vivo, whereas LINC01133 knockdown had the opposite effects. Mechanistically, LINC01133 acted as a sponge of miR-199a-5p, resulting in enhanced expression of SNAI1, which induced epithelial-mesenchymal transition (EMT) in HCC cells. In addition, LINC01133 interacted with Annexin A2 (ANXA2) to activate ANXA2/STAT3 signaling pathway.Conclusions: LINC01133 promotes HCC progression by sponging miR-199a-5p and interacting with ANXA2. LINC01133 CNV gain is predictive of poor prognosis in HCC patients undergoing curative resection.

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CNVs Associated with Susceptibility to Cancers: A Mini-Review

Cited by 7 publications

References 73 publications

A Genome-Wide Association Study to Identify Potential Germline Copy Number Variants for Sporadic Breast Cancer Susceptibility

A Genome-Wide Association Study to Identify Potential Germline Copy Number Variants for Sporadic Breast Cancer Susceptibility

LINC01133 promotes hepatocellular carcinoma progression by sponging miR‐199a‐5p and activating annexin A2

The Long Non-coding RNA LINC01133 Promotes Hepatocellular Carcinoma Progression by Sponging miR-199a-5p and Activating Annexin A2

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