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miR-205-LPCAT1 轴促进多种癌症的增殖和进展。

A miR-205-LPCAT1 axis contributes to proliferation and progression in multiple cancers.

机构信息

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032, Xi'an, China.

State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032, Xi'an, China.

出版信息

Biochem Biophys Res Commun. 2020 Jun 25;527(2):474-480. doi: 10.1016/j.bbrc.2020.04.071. Epub 2020 Apr 23.

Abstract

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.

摘要

在过去的二十年中,miRNA 被证明在恶性疾病的发展和进展中发挥着关键作用。鉴定 miRNA 的作用和机制对于 miRNA 为基础的治疗在癌症中的应用是迫切需要的。miR-205 是一种从无脊椎动物到哺乳动物物种都保守的 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肿瘤抑制作用。我们在这里的目的是阐明 miR-205 在实体瘤中的作用和新机制。在本研究中,我们发现高水平的 miR-205 是 LIHC、HNSCC 和 LUSC 中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 miR-205。结果表明,miR-205 的过表达显著抑制癌细胞增殖。在机制上,我们鉴定出溶血磷脂酰胆碱酰基转移酶-1(LPCAT1)是多种癌细胞中 miR-205 的一个新靶点。此外,我们发现 LPCAT1 是癌细胞持续增殖所必需的,并且高水平的 LPCAT1 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。所有这些发现都使得 miR-205-LPCAT1 轴为癌症治疗提供了一个潜在的治疗靶点。

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