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      LncRNA HAND2-AS1 inhibits non-small cell lung cancer migration, invasion and maintains cell stemness through the interactions with TGF-β1

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          Abstract

          LncRNA HAND2-AS1 is characterized as a tumor suppressor involved in several types of malignancies, but its role in non-small cell lung cancer (NSCLC) is unknown. Our study was carried out to investigate the involvement of lncRNA HAND2-AS1 in NSCLC. In our study, we observed that levels of HAND2-AS1 were lower in tumor tissues than that in adjacent healthy tissues. Compared with healthy controls, plasma levels of HAND2-AS1 were lower, while levels of transforming growth factor β (TGF-β) were higher in NSCLC patients. A significant negative correlation between plasma levels of HAND2-AS1 and TGF-β1 was found in NSCLC patients but not in healthy controls. LncRNA HAND2-AS1 overexpression inhibits, while exogenous TGF-β1 treatment promotes cell migration and invasion ability and cancer cell stemness. Cancer cells with lncRNA HAND2-AS1 overexpression showed down-regulated TGF-β1, while TGF-β1 treatment showed no significant effects on lncRNA HAND2-AS1 expression. TGF-β1 attenuated the inhibitory effects of lncRNA HAND2-AS1 overexpression on cell migration, invasion and stemness. We concluded that lncRNA HAND2-AS1 may regulate the migration, invasion and stemness of NSCLC cells through interactions with TGF-β1.

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          TGF-beta signaling in cancer--a double-edged sword.

          Transforming growth factor (TGF) beta1 is a potent growth inhibitor, with tumor-suppressing activity. Cancers are often refractile to this growth inhibition either because of genetic loss of TGF-beta signaling components or, more commonly, because of downstream perturbation of the signaling pathway, such as by Ras activation. Carcinomas often secrete excess TGF-beta1 and respond to it by enhanced invasion and metastasis. Therapeutic approaches should aim to inhibit the TGF-beta-induced invasive phenotype, but also to retain its growth-inhibitory and apoptosis-inducing effects.
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            Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

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              Transforming growth factor β as regulator of cancer stemness and metastasis

              Key elements of cancer progression towards metastasis are the biological actions of cancer stem cells and stromal cells in the tumour microenvironment. Cross-communication between tumour and stromal cells is mediated by secreted cytokines, one of which, the transforming growth factor β (TGFβ), regulates essentially every cell within the malignant tissue. In this article, we focus on the actions of TGFβ on cancer stem cells, cancer-associated fibroblasts and immune cells that assist the overall process of metastatic dissemination. We aim at illustrating intricate connections made by various cells in the tumour tissue and which depend on the action of TGFβ.
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                Author and article information

                Journal
                Biosci Rep
                Biosci. Rep
                ppbioscirep
                BSR
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                03 December 2018
                31 January 2019
                11 January 2019
                : 39
                : 1
                : BSR20181525
                Affiliations
                Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
                Author notes
                Correspondence: Zhiming Chen ( hnltsq3@ 123456163.com ) or Liewen Pang ( uufhb43@ 123456163.com )
                Author information
                http://orcid.org/0000-0001-8213-1271
                Article
                10.1042/BSR20181525
                6328884
                30509963
                54616ec0-d0fa-4ef8-aa6c-6933ab05a5a9
                © 2019 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
                : 03 September 2018
                : 02 November 2018
                : 11 November 2018
                Page count
                Pages: 8
                Categories
                Research Articles
                Research Article
                8
                39
                46
                13

                Life sciences
                invasion,lncrna hand2-as1,migration,non-small cell lung cancer,tgf-β1
                Life sciences
                invasion, lncrna hand2-as1, migration, non-small cell lung cancer, tgf-β1

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