A miR-205-LPCAT1 axis contributes to proliferation and progression in multiple cancers
A miR-205-LPCAT1 axis contributes to proliferation and progression in multiple cancers
复制标题
miR-205-LPCAT1 轴有助于多种癌症的增殖和进展
DOI：
10.1016/j.bbrc.2020.04.071
复制
发表时间：
2020-06-25
影响因子：
3.1
通讯作者：
Zhang, Rui
中科院分区：
文献类型：
--
作者：
Liu, Fang;Wu, Ye;Zhang, Rui
在过去的二十年中，mirna已被证明在恶性疾病的发生和进展中发挥关键作用。明确miRNA在肿瘤中的作用和作用机制是miRNA在肿瘤治疗中应用的迫切需要。MiR-205是一种从无脊椎动物到哺乳动物的保守miRNA。先前的研究表明，大量证据表明它在不同类型的癌症中具有致癌或抑制肿瘤的作用。我们的目的是阐明miR-205在实体肿瘤中的作用和新的机制。在本研究中，我们发现高水平的miR-205是LIHC、HNSCC和LUSC预后良好的独立生物标志物。在功能实验中，我们在上述癌症来源的肿瘤细胞系中稳定表达了miR-205。结果表明，过表达miR-205可显著抑制癌细胞增殖。在机制上，我们发现溶血磷脂酰胆碱酰基转移酶1 （LPCAT1）是多种癌细胞中miR-205的新靶点。此外，我们发现LPCAT1是癌细胞持续增殖所必需的，其高水平与临床患者的不良预后密切相关。总之，我们揭示了miR-205-LPCAT1轴在多种癌症中的重要预后价值，并强调了LPCAT1在mir -205调节的癌细胞增殖中的重要作用。所有这些发现使得miR-205-LPCAT1轴揭示了癌症治疗的潜在治疗靶点。(C) 2020爱思唯尔公司版权所有。
In the past two decades, miRNAs have been demonstrated to play critical roles in development and progression of malignant diseases. To identify the role and mechanism of miRNA are urgent for the application of miRNA-based therapeutics in cancers. MiR-205 is a conserved miRNA from the invertebrate to mammalian species. Previous studies showed a large body of evidence to demonstrate the oncogenic or tumor suppressive role of it in different types of cancers. Our aim here is to clarify the role and novel mechanism of miR-205 in solid tumors. In the present study, we found that a high level of miR-205 is an independent biomarker for favorable prognosis in LIHC, HNSCC and LUSC. In the functional experiment, we stably expressed miR-205 in tumor cell lines derived from above mentioned cancers. The result showed that overexpression of miR-205 significantly inhibits cancer cell proliferation. Mechanistically, we identified that the lysophosphatidylcholine acyltransferase-1 (LPCAT1) is a novel target of miR-205 in multiple cancer cells. Furthermore, we found that LPCAT1 is required for sustained proliferation of cancer cells and a high level of it is closely associated with poor prognosis in clinical patients. Collectively, we revealed the important prognostic value of a miR-205-LPCAT1 axis in multiple cancers and highlighted an essential role of LPCAT1 in miR-205-regulated cancer cell proliferation. All these discoveries make a miR-205-LPCAT1 axis to shed light upon a potential therapeutic target in cancer treatment. (C) 2020 Elsevier Inc. All rights reserved.