Hepatocellular carcinoma associated microRNA expression signature: integrated bioinformatics analysis, experimental validation and clinical significance

Shi, Ke‐Qing; Lin, Zhuo; Chen, Xiangjian; Song, Mei; Wang, Yu-Qun; Cai, Yiqi; Yang, Nai-Bing; Zheng, Ming‐Hua; Dong, Jin-Zhong; Zhang, Lei; Chen, Yongping

doi:10.18632/oncotarget.4437

Cited by 90 publications

(69 citation statements)

References 53 publications

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“…This may attribute to the limitations of data mining algorithm and different test methods mentioned in many related reports5556. The qRT-PCR results of cell lines basically corresponded to microarray data.…”

Section: Discussionmentioning

confidence: 97%

Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer: integrated bioinformatics analysis, experimental validation and diagnostic evaluation

Dai

Chen

et al. 2017

Sci Rep

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The aim of this study is to explore the differentially expressed lncRNAs, which may have potential biological function and diagnostic value in colorectal cancer (CRC). Through integrated data mining, we finally identified nine differentially expressed lncRNAs and their potential mRNA targets. After a series of bioinformatics analyses, we screened significant pathways and GO terms that are related to the up-regulated and down-regulated transcripts respectively. Meanwhile, the nine lncRNAs were validated in 30 paired tissues and cell lines by qRT-PCR and the results were basically consistent with the microarray data. We also tested the nine lncRNAs in the serum of 30 CRC patients matched with the CRC tissue, 30 non-cancer patients and 30 health controls. Finally, we found that BLACAT1 was significant for the diagnosis of CRC. The area under the curve (AUC), sensitivity and specificity were 0.858 (95% CI: 0.765–0.951), 83.3% and 76.7% respectively between CRC patients and health controls. Moreover, BLACAT1 also had distinct value to discriminate CRC from other non-cancer diseases. The results indicated that the differentially expressed lncRNAs and their potential target transcripts could be considered as potential therapeutic targets for CRC patients. Meanwhile, lncRNA BLACAT1 might represent a new supplementary biomarker for the diagnosis of CRC.

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Section: Discussionmentioning

confidence: 97%

Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer: integrated bioinformatics analysis, experimental validation and diagnostic evaluation

Dai

Chen

et al. 2017

Sci Rep

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“…We further validated aberrant expression patterns of these miRNAs in the TCGA-COAD dataset [17]. We distinguished miR-195-5p as a clinically noteworthy miRNA in CRC as found in lung cancer [18].…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis identifies microRNA-195 as a suppressor of Hippo-YAP pathway in colorectal cancer

et al. 2017

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BackgroundWith persistent inconsistencies in colorectal cancer (CRC) miRNAs expression data, it is crucial to shift toward inclusion of a “pre-laboratory” integrated analysis to expedite effective precision medicine and translational research. Aberrant expression of hsa-miRNA-195 (miR-195) which is distinguished as a clinically noteworthy miRNA has previously been observed in multiple cancers, yet its role in CRC remains unclear.MethodsIn this study, we performed an integrated analysis of seven CRC miRNAs expression datasets. The expression of miR-195 was validated in The Cancer Genome Atlas (TCGA) datasets, and an independent validation sample cohort. Colon cancer cells were transfected with miR-195 mimic and inhibitor, after which cell proliferation, colony formation, migration, invasion, and dual luciferase reporter were assayed. Xenograft mouse models were used to determine the role of miR-195 in CRC tumorigenicity in vivo.ResultsFour downregulated miRNAs (hsa-let-7a, hsa-miR-125b, hsa-miR-145, and hsa-miR-195) were demonstrated to be potentially useful diagnostic markers in the clinical setting. CRC patients with a decreased level of miR-195-5p in tumor tissues had significantly shortened survival as revealed by the TCGA colon adenocarcinoma (COAD) dataset and our CRC cohort. Overexpression of miR-195-5p in DLD1 and HCT116 cells repressed cell growth, colony formation, invasion, and migration. Inhibition of miR-195-5p function contributed to aberrant cell proliferation, migration, invasion, and epithelial mesenchymal transition (EMT). We identified miR-195-5p binding sites within the 3’-untranslated region (3′-UTR) of the human yes-associated protein (YAP) mRNA. YAP1 expression was downregulated after miR-195-5p treatment by qRT-PCR analysis and western blot.ConclusionsFour downregulated miRNAs were shown to be prime candidates for a panel of biomarkers with sufficient diagnostic accuracy for CRC in a clinical setting. Our integrated microRNA profiling approach identified miR-195-5p independently associated with prognosis in CRC. Our results demonstrated that miR-195-5p was a potent suppressor of YAP1, and miR-195-5p-mediated downregulation of YAP1 significantly reduced tumor development in a mouse CRC xenograft model. In the clinic, miR-195-5p can serve as a prognostic marker to predict the outcome of the CRC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0445-8) contains supplementary material, which is available to authorized users.

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“…Previous studies mainly focused on one type of RNA. Various prognostic risk models based on lncRNAs [25], miRNAs [26,27] and mRNAs [28] have been proposed by different scholars. However, the prognostic value of a PI including different kinds of RNA is still not clear.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Analysis of Prognostic lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in Hepatocellular Carcinoma

Lin

Wen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hepatocellular carcinoma (HCC) is the most prevalent subtype of primary liver tumor worldwide. Growing evidence has led to a consensus that long non-coding RNAs (lncRNAs) have considerable influence on tumorigenesis and tumor progression of HCC via the mechanism of competing endogenous RNAs (ceRNAs). Methods: Here, we systematically investigated the expression landscape and clinical prognostic value of lncRNAs, micorRNAs (miRNAs), and mRNAs from The Cancer Genome Atlas. Differentially expressed RNAs were submitted to Cox regression analysis and the construction of prognostic indexes. A lncRNA-miRNA-mRNA regulatory network was then constructed based on interaction information derived from miRcode, TargetScan, miRTarBase, and miRDB. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to reveal and determine the functional roles of the ceRNA network in the prognosis of HCC. Results: We detected 77 differentially expressed lncRNAs, 29 differentially expressed miRNAs, and 1014 differentially expressed mRNAs in HCC, which were significantly associated with the overall survival of patients with HCC. We developed three prognostic prediction models that showed moderate predicting prognosis performance and were highly correlated with tumor burden, histological grade and pathological stage. Additionally, 10 survival-related lncRNAs, 6 survival-related miRNAs, and 31 survival-related mRNAs were included to develop a ceRNA network. Further functional enrichment analysis suggested that the ceRNA network was associated with a dismal prognosis for patients with HCC by disturbing the homeostasis of the cell cycle. Conclusion: Together, our study highlights the significant roles of lncRNAs in the development and implementation of monitoring surveillance and prognosis of HCC and provides a deeper understanding of the lncRNA-related ceRNA regulatory mechanism in the pathogenesis of HCC.

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Hepatocellular carcinoma associated microRNA expression signature: integrated bioinformatics analysis, experimental validation and clinical significance

Cited by 90 publications

References 53 publications

Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer: integrated bioinformatics analysis, experimental validation and diagnostic evaluation

Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer: integrated bioinformatics analysis, experimental validation and diagnostic evaluation

Integrated analysis identifies microRNA-195 as a suppressor of Hippo-YAP pathway in colorectal cancer

Genome-Wide Analysis of Prognostic lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in Hepatocellular Carcinoma

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