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      Long non-coding RNA linc-ITGB1 promotes cell proliferation, migration, and invasion in human hepatoma carcinoma by up-regulating ROCK1

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      , ,
      Bioscience Reports
      Portland Press Ltd.
      hepatoma carcinoma, invasion, Linc-ITGB1, migration, proliferation, ROCK1

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          Abstract

          Background: Linc-ITGB1 is a newly identified long non-coding RNA (lncRNA) involved in the regulation of cell migration and invasion of gallbladder cancer cell lines, while its involvement in human hepatoma carcinoma (HCC) is unknown. Methods: In the present study, HCC patient tumor tissues, adjacent healthy tissues and whole blood were collected from both HCC patients and healthy controls. Expression of LINC-ITGB1 was examined by qRT-PCR. Diagnostic value of serum LINC-ITGB1 for HCC was evaluated by receiver operating characteristic (ROC) curve analysis. Correlation between the serum LINC-ITGB1 and basic clinical information of patients was analyzed by chi-square test. LINC-ITGB1 overexpression HCC cell lines were established and the effects on cell proliferation, migration, and invasion were explored by CCK-8 assay and Transwell assay. Effects of LINC-ITGB1 overexpression on Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) expression were investigated by Western blot. Results: We found that LINC-ITGB1 was up-regulated in tumor tissues than in adjacent healthy tissues. Serum levels of LINC-ITGB1 were higher in HCC patients than in healthy controls. Serum levels of LINC-ITGB1 were significantly correlated with tumor size and distant tumor metastasis. LINC-ITGB1 overexpression promoted the proliferation, migration, and invasion of HCC cells and the expression of ROCK1. ROCK1 inhibitor reduced the effects of LINC-ITGB1 overexpression on cell proliferation, migration, and invasion. Conclusion: We conclude that lncRNA LINC-ITGB1 can promote the proliferation, migration, and invasion of HCC cells by up-regulating ROCK1.

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          Most cited references14

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          Emerging trends in hepatocellular carcinoma incidence and mortality.

          The rise in incidence of hepatocellular carcinoma (HCC) in the United States has been well documented. The purpose of this analysis was to examine temporal trends in HCC incidence, mortality, and survival within the U.S. population. The Surveillance, Epidemiology, and End Results data were used to examine incidence and incidence-based (IB) mortality in HCC from 1973 to 2011. Secular trends in age-adjusted incidence and IB mortality by sex and cancer stage were characterized using the Joinpoint Regression program. In 1973, HCC incidence was 1.51 cases per 100,000, whereas in 2011, HCC incidence was 6.20 cases per 100,000. Although HCC incidence continues to increase, a slowing of the rate of increase occurs around 2006. In a sensitivity analysis, there was no significant increase in incidence and IB mortality from 2009 to 2011. There was a significant increase in overall median survival from the 1970s to 2000s (2 vs. 8 months; P < 0.001). On multivariable Cox's regression analysis, age, sex, race, tumor grade, stage at diagnosis, lymph/vascular invasion, number of primary tumors, tumor size, and liver transplant were independently associated with mortality.
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            ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma.

            Proinflammatory cytokines are frequently observed in the tumor microenvironment, and chronic inflammation is involved in cancer initiation and progression. We show that cytokine signaling through the receptor subunit GP130-IL6ST and the kinase JAK1 generates actomyosin contractility through Rho-kinase dependent signaling. This pathway generates contractile force in stromal fibroblasts to remodel the extracellular matrix to create tracks for collective migration of squamous carcinoma cells and provides the high levels of actomyosin contractility required for migration of individual melanoma cells in the rounded, "amoeboid" mode. Thus, cytokine signaling can generate actomyosin contractility in both stroma and tumor cells. Strikingly, actomyosin contractility itself positively modulates activity of the transcription factor STAT3 downstream of JAK1, demonstrating positive feedback within the signaling network. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin.

              The hepatitis B virus X protein (HBx) has been implicated as an oncogene in both epigenetic modifications and genetic regulation during hepatocarcinogenesis, but the underlying mechanisms are not entirely clear. Long noncoding RNAs (lncRNAs), which regulate gene expression with little or no protein-coding capacity, are involved in diverse biological processes and in carcinogenesis. We asked whether HBx could promote hepatocellular carcinoma (HCC) by regulating the expression of lncRNAs. In this study we investigated the alteration in expression of lncRNAs induced by HBx using microarrays and real-time quantitative polymerase chain reaction (PCR). Our results indicate that HBx transgenic mice have a specific profile of liver lncRNAs compared with wildtype mice. We identified an lncRNA, down-regulated expression by HBx (termed lncRNA-Dreh), which can inhibit HCC growth and metastasis in vitro and in vivo, act as a tumor suppressor in the development of hepatitis B virus (HBV)-HCC. LncRNA-Dreh could combine with the intermediate filament protein vimentin and repress its expression, and thus further change the normal cytoskeleton structure to inhibit tumor metastasis. We also identified a human ortholog RNA of Dreh (hDREH) and found that its expression level was frequently down-regulated in HBV-related HCC tissues in comparison with the adjacent noncancerous hepatic tissues, and its decrement significantly correlated with poor survival of HCC patients. These findings support a role of lncRNA-Dreh in tumor suppression and survival prediction in HCC patients. This discovery contributes to a better understanding of the importance of the deregulated lncRNAs by HBx in HCC and provides a rationale for the potential development of lncRNA-based targeted approaches for the treatment of HBV-related HCC. Copyright © 2012 American Association for the Study of Liver Diseases.
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                Author and article information

                Journal
                Biosci Rep
                Biosci. Rep
                ppbioscirep
                BSR
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                02 October 2018
                31 October 2018
                31 October 2018
                : 38
                : 5
                : BSR20181289
                Affiliations
                Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing 100044, P.R. China
                Author notes
                Correspondence: Lei Huang ( jemst83@ 123456163.com )
                [*]

                These authors contributed equally to this work and should be considered co-first authors.

                Article
                10.1042/BSR20181289
                6209605
                30279202
                62ccb129-8a9d-4657-880a-4dc0ba66221e
                © 2018 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 28 July 2018
                : 11 September 2018
                : 12 September 2018
                Page count
                Pages: 10
                Categories
                Research Articles
                Research Article
                39
                46
                48

                Life sciences
                hepatoma carcinoma,invasion,linc-itgb1,migration,proliferation,rock1
                Life sciences
                hepatoma carcinoma, invasion, linc-itgb1, migration, proliferation, rock1

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