The pseudogene derived long noncoding RNA DUXAP8 promotes gastric cancer cell proliferation and migration via epigenetically silencing PLEKHO1 expression

Ma, Hongwei; Xie, Min; Sun, Ming; Chen, Tianyu; Jin, Renshun; Ma, Tianshi; Chen, Qinnan; Zhang, Erbao; He, Xu; De, Wei; Zhang, Zhihong

doi:10.18632/oncotarget.11075

Cited by 91 publications

(93 citation statements)

References 41 publications

(40 reference statements)

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“…Interestingly, these processes are closely related to cancer cells proliferation and invasion. As well as our findings, Sun et al24 reported that DUXAP8 promotes cell proliferation and invasion through repressing EGR1 and RHOB expression in human non small cell lung cancer; Ma et al25 found that DUXAP8 promotes cell proliferation through epigenetically silencing PLEKHO1 expression in gastric cancer. In addition, Kong and colleagues27 revealed that LINC00460 facilitates tumorigenesis by sponging miR‐149‐5p to up‐regulate IL6 in nasopharyngeal carcinoma; Liang et al28 reported that LINC00460 expression is upregulated in ESCC tissues and positively correlated with lymph node metastasis.…”

Section: Discussionsupporting

confidence: 90%

“…Among these increased lncRNAs, we found that DUXAP8 and LINC00460 are consistently upregulated in TCGA data and three GEO datasets (Figure 4A,B). Interestingly, DUXAP8 has also been reported to be overexpressed in human non small cell lung cancer,24 gastric cancer25 and renal cell carcinoma,26 while LINC00460 expression is upregulated in nasopharyngeal carcinoma27 and promotes carcinogenesis in ESCC 28. Therefore, we chose these two lncRNAs for further analyses and validation.…”

Section: Resultsmentioning

confidence: 99%

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A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

et al. 2018

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Esophageal cancer is one of the most common cancers and a leading cause of cancer‐related death worldwide. However, the mechanism of esophageal cancer pathogenesis remains poorly understood. Long noncoding RNAs (lncRNAs) dysregulation have been reported to involve in various human cancers, which highlights the potential of lncRNAs used as novel biomarkers for cancer diagnosis. Although more efforts have been made to identify novel lncRNAs signature in esophageal cancer, the expression pattern, prognostic value, and biological function of most lncRNAs in esophageal cancer still need to be systematically investigated. In this study, we comprehensively analyzed the expression profile of lncRNAs in more than 200 esophageal cancer patients tissue samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We identified thousands of lncRNAs are differentially expressed in esophageal cancer tissues, and many of those lncRNAs expression are associated with patients overall survival or recurrence‐free survival time. Moreover, copy number variation analyses revealed that genomic loci copy number amplification or deletion might contribute to these lncRNAs dysregulation. Among these lncRNAs, DUXAP8 and LINC00460 were significantly upregulated, and GO enrichment analyses indicated that the two lncRNAs associated protein‐coding genes involve with many known biological processes, such as cell cycle and cell‐cell adherens junction. Further experimental validation revealed that knockdown of DUXAP8 could impair esophageal cancer cells proliferation and invasion in vitro. Taken together, our findings identified more aberrantly expressed lncRNAs in esophageal cancer that may provide a useful resource for identifying novel esophageal cancer associated lncRNAs.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

et al. 2018

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“…Recent studies have revealed that expression alterations of lncRNAs are among the driving forces of tumorigenesis. Our previous study identified a pseudogene-derived lncRNA, DUXAP8, that promotes cell proliferation and migration by associating with PRC2 to epigenetically silence PLEKHO1 expression in gastric cancer (GC) [20]. Moreover, lncRNA HOXA-AS2 promotes GC cell proliferation via epigenetically inhibiting P21/PLK3/DDIT3 [21].…”

Section: Discussionmentioning

confidence: 99%

The Long Intergenic Noncoding RNA 00707 Promotes Lung Adenocarcinoma Cell Proliferation and Migration by Regulating Cdc42

Zou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Lung cancer (LC) is a serious disease with high morbidity and mortality. Long noncoding RNAs (lncRNAs) have garnered attention because they participate in diverse human disorders, including cancer. Our study examined the long intergenic noncoding RNA 00707 (LINC00707). The effects of LINC00707 on lung adenocarcinoma (LAD) and molecular mechanisms are unclear. This study is aimed to investigate the role of LINC00707 in the malignant processes of LAD. Methods: Quantitative reverse transcription PCR (qRT-PCR) was used to examine the expression level of LINC00707 in tissues and cell lines. The association of LINC00707 expression and postoperative prognosis was analyzed by the Kaplan-Meier method and log-rank test. Cell proliferation was evaluated in vitro and in vivo. Transwell assays were performed to examine cell migration. Cell cycle and apoptosis was determined by flow -cytometric and western blot analyses. Microarray analysis was conducted to screen for the downstream target gene Cdc42 of LINC00707, which was identified by qRT-PCR, functional analysis, and rescue experiment. Results: The expression level of LINC00707 was clearly upregulated in LAD tissues compared to that in corresponding normal tissues. Its overexpression was related to advanced TNM stage, larger tumor size, lymphatic metastasis, and poor prognosis. Functional assays revealed that LINC00707 knockdown repressed LAD cell proliferation both in vitro and in vivo. This process may involve the inducing of G1 arrest and apoptosis. Moreover, cell migration was impaired after LINC00707 inhibition. Microarray analysis and rescue assays suggested that Cdc42 is an important target gene involved in the carcinogenesis of LINC00707. Conclusions: In summary, LINC00707 is a noncoding oncogene that exerts important regulatory functions in LAD, suggesting its potential as a biomarker in the prognosis and treatment of LAD.

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“…In recent years, the role of lncRNA double homeobox A pseudogene 8 (DUXAP8) has been gradually studied in cancers. Studies show that DUXAP8 exerts a regulatory role in esophageal squamous cell carcinoma, renal cell carcinoma, gastric cancer, and other tumors . A recent study reports that in HCC, DUXAP8 repressed tumor suppressor KLF2 transcription through interacting with EZH2 .…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA DUXAP8 contributes to the progression of hepatocellular carcinoma via regulating miR‐422a/PDK2 axis

et al. 2020

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Background Hepatocellular carcinoma (HCC) is one of the most deadly cancer worldwide. Multiple long noncoding RNAs (lncRNAs) are recently identified as crucial oncogenic factors or tumor suppressors. In this study, we explored the functon and mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in the progression of HCC. Methods Expression levels of DUXAP8 in HCC tissue samples were measured using qRT‐PCR. The association between pathological indexes and the expression of DUXAP8 was also analyzed. Human HCC cell lines SMMC‐7721 and QSG‐7701 were used in in vitro studies. CCK‐8 assay was used to assess the effect of DUXAP8 on HCC cell line proliferation. Scratch healing assay and Transwell assay were conducted to detect the effect of DUXAP8 on migration and invasion. Furthermore, dual‐luciferase reporter assay was used to confirm targeting relationship between miR‐422a and DUXAP8. Additionally, Western blot was used to detect the regulatory function of DUXAP8 on pyruvate dehydrogenase kinase 2 (PDK2). Results DUXAP8 expression HCC clinical samples was significantly increased and this was correlated with unfavorable pathological indexes. High expression of DUXAP8 was associated with shorter overall survival time of patients. Its overexpression remarkably facilitated the proliferation, metastasis, and epithelial‐mesenchymal transition of HCC cells. Accordingly, knockdown of it suppressed the malignant phenotypes of HCC cells. Overexpression of DUXAP8 significantly reduced the expression of miR‐422a by sponging it, but enhanced the expression of PDK2. Conclusions DUXAP8 was a sponge of tumor suppressor miR‐422a in HCC, enhanced the expression of PDK2 indirectly, and functioned as an oncogenic lncRNA.

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The pseudogene derived long noncoding RNA DUXAP8 promotes gastric cancer cell proliferation and migration via epigenetically silencing PLEKHO1 expression

Cited by 91 publications

References 41 publications

A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

The Long Intergenic Noncoding RNA 00707 Promotes Lung Adenocarcinoma Cell Proliferation and Migration by Regulating Cdc42

Long noncoding RNA DUXAP8 contributes to the progression of hepatocellular carcinoma via regulating miR‐422a/PDK2 axis

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