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      MiR-3150b inhibits hepatocellular carcinoma cell proliferation, migration and invasion by targeting GOLPH3

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          Abstract

          Background

          In this study, we aimed to explore the potential involvement of miR-3150b in hepatocellular carcinoma (HCC) carcinogenesis.

          Methods

          The expression of miR-3150b and Golgi phosphoprotein 3 (GOLPH3) was determined in HCC cell lines. Cell proliferation, migration and invasion were estimated by Cell Counting Kit-8, wound healing and Transwell assays. The association between miR-3150b and GOLPH3 was verified by luciferase assay.

          Results

          MiR-3150b was downregulated, while GOLPH3 was remarkably upregulated in HCC cells. Furthermore, miR-3150b inhibited HCC cell proliferation, migration and invasion. MiR-3150b directly targeted and negatively regulated GOLPH3.

          Conclusion

          MiR-3150b suppressed HCC cell proliferation, invasion and migration by targeting GOLPH3.

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          Most cited references20

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          miRNA-487a Promotes Proliferation and Metastasis in Hepatocellular Carcinoma.

          Purpose: Hepatocellular carcinoma (HCC) harbors highly metastatic properties, accounting for postoperative recurrence and metastasis. However, the mechanisms for metastasis and recurrence remain incompletely clear. This study aimed to investigate the role of hsa-miR-487a (miR-487a) in promoting the proliferation and metastasis of HCC and to elucidate the underlying molecular mechanisms.Experimental Design: 198 HCC samples were analyzed for association between miR-487a expression and patient clinicopathological features and prognosis. The roles of miR-487a in proliferation and metastasis were validated both in vivo and in vitro The upstream regulator and downstream targets of miR-487a were determined using a dual luciferase reporter assay, chromatin immunoprecipitation and immunohistochemistry.Results: Our results demonstrate that upregulated miR-487a correlates with a poor prognosis for HCC patients. miR-487a enhances proliferation and metastasis of HCC cells by directly binding to sprouty-related EVH1 domain containing 2 (SPRED2) or phosphoinositide-3-Kinase regulatory subunit 1 (PIK3R1). Interestingly, miR-487a mainly promotes metastasis via SPRED2 induced mitogen activated protein kinase signaling and promotes proliferation via PIK3R1 mediated AKT signaling. Transcription of miR-487a was found to be activated by up-regulated heat shock factor 1, which we previously demonstrated to be an important metastasis-associated transcription factor in a previous study. Phosphorodiamidate morpholino oligomers effectively silenced miR-487a and inhibited HCC tumor progression in mouse models.Conclusions: Our findings show that miR-487a, mediated by heat shock factor 1, promotes proliferation and metastasis of HCC by PIK3R1 and SPRED2 binding, respectively. Our study provides a rationale for developing miR-487a as a potential prognostic marker or a potential therapeutic target against HCC. Clin Cancer Res; 23(10); 2593-604. ©2016 AACR.
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            Surgical resection and liver transplantation for hepatocellular carcinoma.

            With a better understanding of the natural history of hepatocellular carcinoma (HCC) and the improvement in imaging, locoregional therapies, surgical techniques, and postoperative care, patients with HCC are now managed by a multidisciplinary team. Partial hepatic resection can be curative in patients developing HCC in the setting of normal liver parenchyma and in patients with early cirrhosis but well-preserved hepatic synthetic function. Liver transplantation offers the best long-term survival and lowest incidence of tumor recurrence in select patients with HCC and underlying cirrhosis. This article discusses the role of surgical resection and liver transplantation in the management of HCC.
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              Golgi phosphoprotein 3 (GOLPH3) promotes hepatocellular carcinoma cell aggressiveness by activating the NF-κB pathway.

              Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, in which the NF-κB pathway plays an important role and is constitutively activated. Better understanding of the molecular pathogenesis of HCC and the NF-κB pathway are needed to improve patient outcomes. Herein, we identified an unappreciated protein involved in NF-κB-induced activation, Golgi phosphoprotein 3 (GOLPH3). The mRNA and protein expression levels of GOLPH3 were frequently up-regulated in HCC and GOLPH3 expression correlated closely with clinical stage and survival in both the testing and validation cohorts. Ectopic over-expression of GOLPH3 in PLC/PRF/5 (PLC) and Huh7 HCC cells protected against cisplatin-induced apoptosis, promoted angiogenesis and proliferation and increased the aggressiveness of HCC cells in vitro and in vivo, whereas inhibition of GOLPH3 led to decreased aggressiveness. Through analysis of two published HCC patient profiles, GOLPH3 expression significantly correlated with NF-κB signalling. Furthermore, we demonstrated that GOLPH3 promoted K63-linked polyubiquitination of tumour necrosis factor receptor-associated factor 2 (TRAF2), receptor interacting protein (RIP) and NF-κB essential modulator (NEMO) and substantially sustained the activation of NF-κB in HCC cells. Taken together, our findings provided evidence that GOLPH3 is a prognostic and/or potential therapeutic biomarker for HCC patients and plays an important role in activation of the NF-κB pathway during HCC progression.
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                Author and article information

                Journal
                J Investig Med
                J. Investig. Med
                jim
                jim
                Journal of Investigative Medicine
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                1081-5589
                1708-8267
                March 2020
                5 December 2019
                : 68
                : 3
                : 770-775
                Affiliations
                [1 ] departmentDepartment of General Surgery , Xi’an XD Group Hospital , Xi'an, China
                [2 ] departmentDepartment of Gastroenterology , Xi'an XD Group Hospital , Xi'an, China
                Author notes
                [Correspondence to ] Dr Hongling Su, Department of Gastroenterology, Xi'an XD Group Hospital, Xi'an, shaanxi 710077, China; honglingsu@ 123456126.com
                Author information
                http://orcid.org/0000-0002-1007-691X
                Article
                jim-2019-001181
                10.1136/jim-2019-001181
                7057801
                31806673
                c9e80cdf-034f-4869-8f92-90a00d3977da
                © American Federation for Medical Research 2020. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

                History
                : 19 November 2019
                Categories
                Original Research
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                golgi phosphoprotein 3,hepatocellular carcinoma,migration,mir-3150b,proliferation

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