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FGD5-AS1 通过调控 BST2 抑制巨噬细胞 M1 极化促进宫颈癌的进展。

Activation of FGD5-AS1 Promotes Progression of Cervical Cancer through Regulating BST2 to Inhibit Macrophage M1 Polarization.

机构信息

Outpatient Department, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

Department of Gynaecology and Obstetrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Immunol Res. 2021 Oct 15;2021:5857214. doi: 10.1155/2021/5857214. eCollection 2021.

Abstract

Accumulating evidence has elucidated the biological function of lncRNAs in various tumors. FGD5 antisense RNA 1 (FGD5-AS1) is identified as a significant tumor regulator in malignancies. Up to now, the detailed function of FGD5-AS1 in cervical cancer and its underlying molecular mechanisms remain uninvestigated. Bone marrow stromal cell antigen 2 (BST2) can play critical roles in immune response, and the roles of BST2 in cervical cancer was explored currently. The level of FGD5-AS1 and BST2 was detected by qRT-PCR in cervical cancer cells. FGD5-AS1 and BST2 expression was significantly upregulated in cervical cancer cells. Then, the decrease of FGD5-AS1 greatly repressed cervical cancer cell growth in vitro. In addition, FGD5-AS1 silencing repressed BST2 expression and suppressed M2 macrophage polarization. Mechanistically, we confirmed that FGD5-AS1 sponged miR-129-5p to reduce its inhibition on BST2. Furthermore, lack of BST2 depressed cervical cancer cell growth, while inducing apoptosis. Loss of BST2 induced M1 macrophage polarization while blocking M2 macrophage polarization. For another, we demonstrated that FGD5-AS1-triggered M2 macrophage polarization was remarkably reversed by miR-129-5p via suppressing BST2. In conclusion, FGD5-AS1 induced M2 macrophage polarization via sponging miR-129-5p and modulating BST2, thus contributing to cervical cancer development. Our findings revealed FGD5-AS1/miR-129-5p/BST2 as a new potential target for cervical cancer.

摘要

越来越多的证据阐明了 lncRNAs 在各种肿瘤中的生物学功能。FGD5 反义 RNA1(FGD5-AS1)被鉴定为恶性肿瘤中重要的肿瘤调节因子。到目前为止,FGD5-AS1 在宫颈癌中的详细功能及其潜在的分子机制仍未被研究。骨髓基质细胞抗原 2(BST2)在免疫反应中可以发挥关键作用,目前正在探索 BST2 在宫颈癌中的作用。通过 qRT-PCR 在宫颈癌细胞中检测 FGD5-AS1 和 BST2 的水平。宫颈癌细胞中 FGD5-AS1 和 BST2 的表达明显上调。然后,FGD5-AS1 的减少极大地抑制了宫颈癌细胞的体外生长。此外,FGD5-AS1 沉默抑制 BST2 的表达并抑制 M2 巨噬细胞极化。在机制上,我们证实 FGD5-AS1 可以作为 miR-129-5p 的海绵,从而减少其对 BST2 的抑制作用。此外,缺乏 BST2 会抑制宫颈癌细胞的生长,同时诱导细胞凋亡。BST2 的缺失诱导 M1 巨噬细胞极化,同时阻止 M2 巨噬细胞极化。另一方面,我们证明 FGD5-AS1 诱导的 M2 巨噬细胞极化通过抑制 BST2 被 miR-129-5p 显著逆转。总之,FGD5-AS1 通过海绵 miR-129-5p 并调节 BST2 诱导 M2 巨噬细胞极化,从而促进宫颈癌的发展。我们的研究结果表明,FGD5-AS1/miR-129-5p/BST2 作为一种新的宫颈癌潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f6e/8536446/8a2b7fd33a41/JIR2021-5857214.001.jpg

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