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LINC00839 通过在低氧条件下结合 FMNL2 促进肝癌的恶性转化。

LINC00839 promotes malignancy of liver cancer via binding FMNL2 under hypoxia.

机构信息

Guangxi University of Chinese Medicine, Nanning, China.

The First Clinical Faculty of Guangxi, University of Chinese Medicine, Nanning, China.

出版信息

Sci Rep. 2022 Nov 5;12(1):18757. doi: 10.1038/s41598-022-16972-z.

Abstract

Liver cancer is one of the most common malignant tumors in the world and metastasis is the leading cause of death associated with liver cancer. Hypoxia is a common feature of solid tumors and enhances malignant character of cancer cells. However, the exact mechanisms involved in hypoxia-driven liver cancer progression and metastasis have not been well clarified so far. The aim of this study was to investigate the contribution of long non-coding RNA (lncRNA) in hypoxia promoting liver cancer progression. We screened and revealed LINC00839 as a novel hypoxia-responsive lncRNA in liver cancer. LINC00839 expression was up-regulated in liver cancer tissues and cell lines, and the patients with high LINC00839 expression had shortened overall survival. LINC00839 further overexpressed under hypoxia and promoted liver cancer cell proliferation, migration, and invasion. Mechanistically, LINC00839 bound multiple proteins that were primarily associated with the metabolism and RNA transport, and positively regulated the expression of Formin-like protein 2 (FMNL2). LINC00839 could promote hypoxia-mediated liver cancer progression, suggesting it may be a clinically valuable biomarker and serve as a molecular target for the diagnosis, prognosis, and therapy of liver cancer.

摘要

肝癌是世界上最常见的恶性肿瘤之一,转移是与肝癌相关的主要死亡原因。缺氧是实体肿瘤的常见特征,并增强了癌细胞的恶性特征。然而,迄今为止,缺氧驱动的肝癌进展和转移的确切机制尚不清楚。本研究旨在探讨长链非编码 RNA(lncRNA)在缺氧促进肝癌进展中的作用。我们筛选并揭示了 LINC00839 是肝癌中一种新的缺氧反应性 lncRNA。LINC00839 在肝癌组织和细胞系中表达上调,高表达 LINC00839 的患者总生存期缩短。LINC00839 在缺氧下进一步过表达,并促进肝癌细胞的增殖、迁移和侵袭。机制上,LINC00839 与主要与代谢和 RNA 转运相关的多种蛋白结合,并正向调节formin 样蛋白 2(FMNL2)的表达。LINC00839 可促进缺氧介导的肝癌进展,表明其可能是一种有临床价值的生物标志物,并可作为肝癌诊断、预后和治疗的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce94/9637198/7d4db9166e44/41598_2022_16972_Fig1_HTML.jpg

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