Integrated analysis of a competing endogenous RNA network reveals key long noncoding RNAs as potential prognostic biomarkers for hepatocellular carcinoma

Ye, Jiaxiang; Zhang, Jinyan; Lv, Yufeng; Wei, Jiazhang; Shen, Xiaofeng; Huang, Junqi; Wu, Susu; Luo, Xi

doi:10.1002/jcb.28655

Cited by 37 publications

(30 citation statements)

References 29 publications

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“…It was originally reported in the Mammalian Gene Collection project of the National Institutes of Health, with the purpose of identifying putative alternative promoters for human genes, but no detailed study is yet available [ 5 , 6 ]. Recently, an overall survival (OS) risk scoring system for HCC patients has been constructed based on the expression of 6 lncRNAs including MYLK-AS1 [ 7 ]. According to reports, MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma

Teng

Zhang

Chang

et al. 2020

J Exp Clin Cancer Res

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Background Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined. Methods Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis. Results MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies. Conclusions MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.

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Section: Introductionmentioning

confidence: 99%

LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma

Teng

Zhang

Chang

et al. 2020

J Exp Clin Cancer Res

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“…28 The previous reports have suggested a controversial role of PART1 in cancers. For instance, Hu et al found that PART1 was overexpressed in bladder cancer specimens and silencing of PART1 led to cell proliferation inhibition and apoptosis in bladder cancer cells; 29 data mining of TCGA dataset revealed that higher expression of PART1 was associated with a higher risk of recurrence for patients with hepatocellular carcinoma; 30 in oral squamous cell carcinoma, however, patients with higher expression of PART1 exhibited longer overall survival compared with patients with lower expression of PART1. 31 Although one study indicated that higher expression of PART1 was associated with longer survival in patients with GBM, 32 the role and molecular mechanisms of PART1 in glioma are not known.…”

Section: Discussionmentioning

confidence: 99%

<p>Long Non-Coding RNA PART1 Exerts Tumor Suppressive Functions in Glioma via Sponging miR-190a-3p and Inactivation of PTEN/AKT Pathway</p>

Jin

Piao

Sun

et al. 2020

OTT

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Background: Glioma is the most commonly diagnosed primary brain tumor. Dysregulation of long non-coding RNA (lncRNA) is associated with initiation and development of various cancer types including glioma. Methods: The relative expression of lncRNA was analyzed by real time-quantitative polymerase chain reaction (RT-qPCR). Cell counting kit (CCK-8) and flow cytometry analysis were applied to explore the role of prostate androgen-regulated transcript 1 (PART1) in glioma cell lines. Luciferase reporter assay, Western blotting and RT-qPCR were used to investigate the association between PART1, miR-190a-3p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in glioma cell lines. Results: In the present study, we elucidated a pivotal role and molecular mechanism of lncRNA PART1 in glioma cell lines. It was found that PART1 was significantly downregulated in glioma tissues compared to normal tissues according to TCGA data and our RT-qPCR results. The cell-based assays showed that PART1 suppressed cell proliferation and triggered cell apoptosis in glioma cell lines. PART1 inactivated PI3K/AKT cascade in glioma cell lines. Transfection of constitutively activated AKT (Myr-AKT) reversed PART1 induced cell apoptosis and cell growth arrest. The bioinformatic analysis suggested that miR-190a-3p might bind to PART1. In the dual luciferase reporter assay, we validated that PART1 directly bound to miR-190a-3p in glioma cell lines. Furthermore, there was a reciprocal repression between PART1 and miR-190-3p. In addition, PART1 upregulated PTEN and inactivated PI3K/AKT pathway in glioma cell lines. Moreover, silencing of PTEN reversed PART1 overexpression induced cell growth arrest and apoptosis. In glioma tissues, the Pearson Correlation analysis showed that there was a strong-positive correlation between PART1 level and PTEN mRNA level. Conclusion: Taken together, the current study revealed a PART1/miR-190a-3p/PTEN/PI3K/ AKT axis in glioma and provided novel insights for understanding the complex lncRNA-miRNA network in glioma.

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“…Several previous studies constructed risk scoring systems to predict the prognosis of HCC patients (Gu et al, 2018;Liao et al, 2018;Ma et al, 2018;Shi et al, 2018;Sui et al, 2018;Wu et al, 2018b;Zhao et al, 2018;Bai et al, 2019;Yan et al, 2019;Ye et al, 2019;Zhang et al, 2019). However, all these risk scoring systems are based on lncRNAs differentially expressed between HCC and normal samples, while our systems are based on lncRNAs differentially expressed between HCC patients with or without cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

Risk Scoring System based on lncRNA Expression for Predicting Survival in Hepatocellular Carcinoma with Cirrhosis

Wei

et al. 2020

Asian Pac J Cancer Prev

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Objective: This study aims to explore the roles of long non-coding RNAs (lncRNAs) for predicting survival in hepatocellular carcinoma (HCC) patients with cirrhosis. Methods: A set of lncRNAs differentially expressed between HCC patients with or without cirrhosis was identified using expression profiles of The Cancer Genome Atlas database, and these lncRNAs were screened for their risk scoring system to predict recurrence-free survival (RFS) or overall survival (OS). Predictive ability of risk scoring systems was confirmed using uni- and multivariate Cox analyses while adjusting for clinical features. Predictive lncRNAs were analyzed by functional enrichment analysis. Results: Our screen identified 22 lncRNAs that were upregulated in the presence of cirrhosis and 59 that were downregulated. To predict OS of HCC patients with cirrhosis, a risk scoring system was developed with four lncRNAs (LINC02086, LINC00880, LINC01549 and AC136475.3); to predict RFS in these patients, the risk scoring system contained five lncRNAs (SH3RF3-AS1, AC104117.3, AC136475.3, LINC00239 and MRPL23-AS1). All risk scoring systems were associated with an area under the receiver operating characteristic curve > 0.7. Based on uni- and multivariate Cox analyses, the risk scoring system could serve as a significant independent predictor for OS in HCC patients with cirrhosis. Functional enrichment analysis suggested that the lncRNAs in the risk scoring systems are involved primarily in the pathway of Wnt signal and cytokine-cytokine receptor interaction. Conclusion: Risk scoring systems based on lncRNAs can effectively predict OS of HCC patients with cirrhosis. The system should be further developed and validated in larger, preferably multi-site patient populations.

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Integrated analysis of a competing endogenous RNA network reveals key long noncoding RNAs as potential prognostic biomarkers for hepatocellular carcinoma

Cited by 37 publications

References 29 publications

LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma

LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma

<p>Long Non-Coding RNA PART1 Exerts Tumor Suppressive Functions in Glioma via Sponging miR-190a-3p and Inactivation of PTEN/AKT Pathway</p>

Risk Scoring System based on lncRNA Expression for Predicting Survival in Hepatocellular Carcinoma with Cirrhosis

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