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      Long non-coding RNA HULC as a novel serum biomarker for diagnosis and prognosis prediction of gastric cancer

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          Abstract

          Long non-coding RNAs (lncRNAs) have recently emerged as vital players in tumor biology with potential value in cancer diagnosis, prognosis, and therapeutics. The lncRNA HULC (highly up-regulated in liver cancer) is increased in many malignancies, yet its serum expression profile and clinical value in gastric cancer (GC) patients remain unclear. Quantitative real-time polymerase chain reaction (RT-qPCR) for large-scale analysis of the serum expression of HULC in GC patients reliably detected circulating HULC and revealed that it is upregulated in GC patients. A high serum HULC level correlated with tumor size, lymph node metastasis, distant metastasis, tumor-node-metastasis stage, and H. pylori infection. The area under the ROC curve for HULC was up to 0.888, which was higher than that for CEA (0.694) and CA72-4 (0.514). Follow-up detection and Kaplan-Meier curve analysis revealed HULC is a good predictor of GC prognosis. Our present study indicates that circulating HULC may represent a novel serum tumor marker for early diagnosis and monitoring progression and prognosis of GC.

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          Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis.

          Nobuyoshi Kosaka, Haruhisa Iguchi, Takahiro Ochiya (2010)
          In the past several years, the importance of microRNA (miRNA) in cancer cells has been recognized. Proper control of miRNA expression is essential for maintaining a steady state of the cellular machinery. Recently, it was discovered that extracellular miRNAs circulate in the blood of both healthy and diseased patients, although ribonuclease is present in both plasma and serum. Most of the circulating miRNAs are included in lipid or lipoprotein complexes, such as apoptotic bodies, microvesicles, or exosomes, and are, therefore, highly stable. The existence of circulating miRNAs in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function, as well as the meaning of the existence of extracellular miRNAs, remain largely unclear. In this review, we summarize the usefulness of circulating miRNA for cancer diagnosis, prognosis, and therapeutics. Furthermore, we propose a mechanism for the secretion and incorporation of miRNA into the cells. © 2010 Japanese Cancer Association.
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            Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells.

            Feng Yang, Jianwei Bi, Xuchao Xue … (2012)
            Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA H19 is up-regulated in hypoxic stress and in some tumors. However, the contributions of H19 to gastric cancer remain largely unknown. In this study, we assayed the H19 expression level in gastric cancer tissues by real-time PCR, and defined the biological functions by flow cytometry and RNA immunoprecipitation. We demonstrated that H19 levels were markedly increased in gastric cancer cells and gastric cancer tissues compared with normal controls. Moreover, ectopic expression of H19 increased cell proliferation, whereas H19 siRNA treatment contributed to cell apoptosis in AGS cell line. We further verified that H19 was associated with p53, and that this association resulted in partial p53 inactivation. These data suggest an important role for H19 in the molecular etiology of gastric cancer and potential application of H19 in gastric cancer therapy. © 2012 The Authors Journal compilation © 2012 FEBS.
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              Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18.

              Yumei Du, Guangyao Kong, Xiaona You … (2012)
              Long noncoding RNAs (lncRNAs) play crucial roles in human cancers. It has been reported that lncRNA highly up-regulated in liver cancer (HULC) is dramatically up-regulated in hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) contributes importantly to the development of HCC. However, the function of HULC in HCC mediated by HBx remains unclear. Here, we report that HULC is involved in HBx-mediated hepatocarcinogenesis. We found that the expression levels of HULC were positively correlated with those of HBx in clinical HCC tissues. Moreover, we revealed that HBx up-regulated HULC in human immortalized normal liver L-O2 cells and hepatoma HepG2 cells. Luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay showed that HBx activated the HULC promoter via cAMP-responsive element-binding protein. We further demonstrated that HULC promoted cell proliferation by methyl thiazolyl tetrazolium, 5-ethynyl-2'-deoxyuridine, colony formation assay, and tumorigenicity assay. Next, we hypothesized that HULC might function through regulating a tumor suppressor gene p18 located near HULC in the same chromosome. We found that the mRNA levels of p18 were inversely correlated with those of HULC in the above clinical HCC specimens. Then, we validated that HULC down-regulated p18, which was involved in the HULC-enhanced cell proliferation in vitro and in vivo. Furthermore, we observed that knockdown of HULC could abolish the HBx-enhanced cell proliferation through up-regulating p18. Thus, we conclude that the up-regulated HULC by HBx promotes proliferation of hepatoma cells through suppressing p18. This finding provides new insight into the roles of lncRNAs in HBx-related hepatocarcinogenesis.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncotarget
                Journal ID (iso-abbrev): Oncotarget
                Journal ID (publisher-id): Oncotarget
                Journal ID (publisher-id): ImpactJ
                Title: Oncotarget
                Publisher: Impact Journals LLC
                ISSN (Electronic): 1949-2553
                Publication date Collection: 9 August 2016
                Publication date (Electronic): 16 June 2016
                Volume: 7
                Issue: 32
                Pages: 51763-51772
                Affiliations
                1 Medical School of Medicine, Nantong University, Nantong 226000, Jiangsu Province, China
                2 Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong 226000, Jiangsu Province, China
                3 Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong 226000, Jiangsu Province, China
                Author notes
                Correspondence to: Shaoqing Ju, jsq814@ 123456hotmail.com
                Article
                Publisher ID: 10107
                DOI: 10.18632/oncotarget.10107
                PMC ID: 5239513
                PubMed ID: 27322075
                SO-VID: 028c03b3-a154-4a73-94cf-68eb22d1cde5
                Copyright © Copyright: © 2016 Jin et al.
                License:

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

                History
                Date received : 25 January 2016
                Date accepted : 2 May 2016
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: gastric cancer,long non-coding rna,biomarker,hulc
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: gastric cancer, long non-coding rna, biomarker, hulc

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