Pseudogene in cancer: real functions and promising signature

Lu, Xiao‐Jie; Gao, Ai-Mei; Ji, Li-Juan; Jiang, Xu

doi:10.1136/jmedgenet-2014-102785

Cited by 115 publications

(89 citation statements)

References 52 publications

(40 reference statements)

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“…[10][11][12][13][14][15] Interestingly, increasing evidence has indicated that some pseudogenes play critical roles in human diseases, especially cancer. [16][17][18] For example, Poliseno et al 19,20 reported that the pseudogene PTENP1 functions in regulating PTEN by acting as a decoy for PTEN-related miRNAs such as miR-17, miR-21, miR-214, miR-19, and miR-26. Moreover, the OCT4 pseudogene OCT4-pg4 functions as a competing endogenous RNA (ceRNA) and protects the OCT4 transcript from being inhibited by miR-145, thereby promoting the growth and tumorigenicity of hepatocellular carcinoma cells.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

et al. 2017

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Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

et al. 2017

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“…Although once regarded as non-functional junk DNA,46 recent studies revealed that some pseudogenes are aberrantly expressed in cancer47 48 and that pseudogenic RNAs may function in tumorigenicity as antisense RNAs, endogenous small-interference RNAs or ceRNAs 49 50…”

Section: Type Of Cernas and Their Possible Roles In Cancermentioning

confidence: 99%

ceRNA in cancer: possible functions and clinical implications

et al. 2015

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Competing endogenous RNAs (ceRNAs) are transcripts that can regulate each other at post-transcription level by competing for shared miRNAs. CeRNA networks link the function of protein-coding mRNAs with that of non-coding RNAs such as microRNA, long non-coding RNA, pseudogenic RNA and circular RNA. Given that any transcripts harbouring miRNA response element can theoretically function as ceRNAs, they may represent a widespread form of post-transcriptional regulation of gene expression in both physiology and pathology. CeRNA activity is influenced by multiple factors such as the abundance and subcellular localisation of ceRNA components, binding affinity of miRNAs to their sponges, RNA editing, RNA secondary structures and RNA-binding proteins. Aberrations in these factors may deregulate ceRNA networks and thus lead to human diseases including cancer. In this review, we introduce the mechanisms and molecular bases of ceRNA networks, discuss their roles in the pathogenesis of cancer as well as methods of predicting and validating ceRNA interplay. At last, we discuss the limitations of current ceRNA theory, propose possible directions and envision the possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets.

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“…24,25 The relationship between differentially expressed pseudogene transcripts and the expression of parent gene targets was diverse in our data (Table S5). In some instances, the upregulation of a pseudogene was associated with the downregulation of its parent gene.…”

Section: Differential Expression Of Transcripts With Epigenetic Regulmentioning

confidence: 99%

Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia

et al. 2015

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Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children under the age of 15. In addition to genetic aberrations, epigenetic modifications such as DNA methylation are altered in cancer and impact gene expression. To identify epigenetic alterations in ALL, genome-wide methylation profiles were generated using the methylated CpG island recovery assay followed by next-generation sequencing. More than 25,000 differentially methylated regions (DMR) were observed in ALL patients with »90% present within intronic or intergenic regions. To determine the regulatory potential of the DMR, whole-transcriptome analysis was performed and integrated with methylation data. Aberrant promoter methylation was associated with the altered expression of genes involved in transcriptional regulation, apoptosis, and proliferation. Novel enhancer-like sequences were identified within intronic and intergenic DMR. Aberrant methylation in these regions was associated with the altered expression of neighboring genes involved in cell cycle processes, lymphocyte activation and apoptosis. These genes include potential epi-driver genes, such as SYNE1, PTPRS, PAWR, HDAC9, RGCC, MCOLN2, LYN, TRAF3, FLT1, and MELK, which may provide a selective advantage to leukemic cells. In addition, the differential expression of epigenetic modifier genes, pseudogenes, and non-coding RNAs was also observed accentuating the role of erroneous epigenetic gene regulation in ALL.

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Pseudogene in cancer: real functions and promising signature

Cited by 115 publications

References 52 publications

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

ceRNA in cancer: possible functions and clinical implications

Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia

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