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      RNA-sequencing investigation identifies an effective risk score generated by three novel lncRNAs for the survival of papillary thyroid cancer patients

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          Abstract

          Scholars are striving to apply molecular biology involving long non-coding RNA (lncRNA) in the prognostication of papillary thyroid cancer (PTC). However, the clinical role of lncRNAs in the prognostic setting of PTC is still unclear. Herein, a comprehensive inquiry was performed to screen lncRNA expression profiling with 507 PTC patients from The Cancer Genome Atlas RNA-sequencing datasets. A total of 734 lncRNAs were detected to be aberrantly expressed, among which three novel lncRNAs including AC079630.2, CRNDE and CTD-2171N6.1 were markedly related to the progression and survival of PTC. Furthermore, the aberrant expression of these lncRNAs could be verified by other cohorts from gene expression omnibus (GEO) as detected by microarrays. Next, we established a three-lncRNA signature and divided the PTC patients into two subgroups of high- and low-risk. Interestingly, patients with high-risk tended to gain obviously poorer outcome. Most importantly, this three-lncRNA signature was an independent biomarker to predict the patient survival of PTC. The accurate molecular roles of these three lncRNAs remains unclarified and warrants further characterization, but our current data propose that they might play pivotal roles in PTC tumorigenesis and more importantly, these novel lncRNAs are closely related to patients’ survival. These discoveries will have far-reaching consequences with respect to molecular prediction of PTC.

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          Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer

          Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer-host cross talk. The aim of our study was to illustrate the clinical significance of the lncRNA CRNDE-h in exosomes purified from the serum of patients with colorectal cancer (CRC). The study was divided into four parts: (1) The exosome isolated methods and lncRNA detected methods which accurately and reproducibly measure CRC-related exosomal CRNDE-h in serum were optimized in preliminary pilot stage; (2) The stability of exosomal CRNDE-h was evaluated systematically; (3) The origin of exosomal CRNDE-h was explorated in vitro and in vivo; (4) The diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468 patients. In pilot study, our results indicated that exosomal CRNDE-h was detectable and stable in serum of CRC patients, and derived from tumor cells. Then, the increased expression of exosomal CRNDE-h was successfully validated in 148 CRC patients when compared with colorectal benign disease patients and healthy donors. Exosomal CRNDE-h level significantly correlated with CRC regional lymph node metastasis (P = 0.019) and distant metastasis (P = 0.003). Moreover, at the cut-off value of 0.020 exosomal CRNDE-h level of serum, the area under ROC curve distinguishing CRC from colorectal benign disease patients and healthy donors was 0.892, with 70.3% sensitivity and 94.4% specificity, which was superior to carcinoembryogenic antigen. In addition, high exosomal CRNDE-h level has a lower overall survival rates than that for low groups (34.6% vs. 68.2%, P < 0.001). In conclusion, detection of lncRNA CRNDE-h in exosome shed a light on utilizing exosomal CRNDE-h as a noninvasive serum-based tumor marker for diagnosis and prognosis of CRC.
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            CRNDE, a long-noncoding RNA, promotes glioma cell growth and invasion through mTOR signaling.

            The transcripts of the gene Colorectal Neoplasia Differentially Expressed (CRNDE) are recognized as long-noncoding RNAs (lncRNAs), which are expressed in specific regions within the human brain, and are the most upregulated lncRNA in gliomas. However, the underlying regulation and function of CRNDE in gliomas are largely unknown. In this study, the upregulation of CRNDE was confirmed in both primary specimens from glioma patients and in vitro with cell lines. Overexpression of specific CRNDE transcript promotes cell growth and migration in vitro while knockdown of CRNDE expression manifests a repressive function during these cellular processes. The growth promoting effect of CRNDE was also demonstrated in a xenograft mouse model. Mechanistic studies further revealed that histone acetylation in the promoter region might account for the upregulation of CRNDE, and the level of CRNDE expression could be modulated by mammalian Target of Rapamycin (mTOR) signaling in glioma. Thus, our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of glioma.
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              CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis.

              Colorectal neoplasia differentially expressed (CRNDE) is the most upregulated long noncoding RNA (lncRNA) in glioma. Herein, the function and potential molecular mechanisms of CRNDE and miR-384 were illustrated in glioma cells. CRNDE overexpression facilitated cell proliferation, migration, and invasion, while inhibited glioma cells apoptosis. Quantitative real-time polymerase chain reaction (PCR) demonstrated that miR-384 was downregulated in human glioma tissues and glioma cell lines. Moreover, restoration of miR-384 exerted tumor-suppressive functions. In addition, the expression of miR-384 was negatively correlated with CRNDE expression. A binding region between CRNDE and miR-384 was confirmed using luciferase assays. Moreover, CRNDE promoted cell malignant behavior by decreasing miR-384 expression. At the molecular level, treatment by CRNDE knockdown or miR-384 overexpression resulted in a decrease of piwi-like RNA-mediated gene silencing 4 (PIWIL4) protein. Besides, PIWIL4 was identified as a target of miR-384 and plays an oncogenic role in glioma. Similarly, downstream proteins of PIWIL4 such as STAT3, cyclin D1, VEGFA, SLUG, MMP-9, caspase 3, Bcl-2, and bcl-xL were modulated when treated with miR-384 and PIWIL4. Remarkably, CRNDE knockdown combined with miR-384 overexpression led to tumor regression in vivo. Overall, these results depicted a novel pathway mediated by CRNDE in glioma, which may be a potential application for glioma therapy.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                26 September 2017
                26 May 2017
                : 8
                : 43
                : 74139-74158
                Affiliations
                1 Department of Gastrointestinal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
                2 Department of General Surgery, First Affiliated Hospital of Guangxi Medical University (West Branch), Nanning, Guangxi Zhuang Autonomous Region, P.R. China
                3 Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
                4 Department of Ultrasonography, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
                5 Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
                Author notes
                Correspondence to: Jun-Qiang Chen, nnhans@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                18274
                10.18632/oncotarget.18274
                5650329
                751d9d93-9d7e-448d-988d-57f875bca693
                Copyright: © 2017 Luo et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 January 2017
                : 15 May 2017
                Categories
                Research Paper

                Oncology & Radiotherapy
                papillary thyroid cancer,lncrna,prognosis,ac079630.2,crnde
                Oncology & Radiotherapy
                papillary thyroid cancer, lncrna, prognosis, ac079630.2, crnde

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