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长链非编码 RNA HAND2-AS1 通过与 TGF-β1 的相互作用抑制非小细胞肺癌迁移、侵袭并维持细胞干性。

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

机构信息

Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.

Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China

出版信息

Biosci Rep. 2019 Jan 11;39(1). doi: 10.1042/BSR20181525. Print 2019 Jan 31.

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.

摘要

长链非编码 RNA HAND2-AS1 被认为是一种参与多种恶性肿瘤的肿瘤抑制因子,但它在非小细胞肺癌(NSCLC)中的作用尚不清楚。我们的研究旨在探讨 lncRNA HAND2-AS1 在 NSCLC 中的作用。在我们的研究中,我们观察到 HAND2-AS1 在肿瘤组织中的水平低于相邻的健康组织。与健康对照组相比,NSCLC 患者的 HAND2-AS1 血浆水平较低,而转化生长因子β(TGF-β)水平较高。在 NSCLC 患者中发现 HAND2-AS1 血浆水平与 TGF-β1 呈显著负相关,但在健康对照组中则无此相关性。lncRNA HAND2-AS1 的过表达抑制,而外源性 TGF-β1 处理则促进细胞迁移和侵袭能力以及癌细胞干性。过表达 lncRNA HAND2-AS1 的癌细胞显示 TGF-β1 下调,而 TGF-β1 处理对 lncRNA HAND2-AS1 表达没有显著影响。TGF-β1 减弱了 lncRNA HAND2-AS1 过表达对细胞迁移、侵袭和干性的抑制作用。我们得出结论,lncRNA HAND2-AS1 可能通过与 TGF-β1 的相互作用调节 NSCLC 细胞的迁移、侵袭和干性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5622/6328884/2cf0cdd8a0c6/bsr-39-bsr20181525-g1.jpg

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