lncRNA DCST1-AS1 Facilitates Oral Squamous Cell Carcinoma by Promoting M2 Macrophage Polarization through Activating NF-κB Signaling.

lncRNA DCST1-AS1 Facilitates Oral Squamous Cell Carcinoma by Promoting M2 Macrophage Polarization through Activating NF-κB Signaling.
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DOI:
10.1155/2021/5524231
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发表时间:
2021
影响因子:
4.1
通讯作者:
Zou C
Zou C
中科院分区:
医学3区
文献类型:
--
作者:
Ai Y;Liu S;Luo H;Wu S;Wei H;Tang Z;Li X;Zou C

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lncRNA与多种疾病的进展相关,包括口腔鳞状细胞癌(OSCC),其是头颈部的常见鳞状细胞癌。肿瘤相关巨噬细胞和肿瘤细胞是肿瘤微环境的重要组成部分。肿瘤相关巨噬细胞的M2极化是肿瘤恶性和转移的关键因素。本研究旨在探讨lncRNA DCST 1-AS 1在口腔鳞癌中的作用机制。在此,我们报道了DCST 1-AS 1在OSCC细胞中显著增加。我们发现DCST 1-AS 1的缺失明显抑制了OSCC细胞的增殖、迁移和侵袭以及异种移植瘤的生长。同时,DCST 1-AS 1的沉默也抑制了表达M2标志物CD 206和CD 11b的巨噬细胞的百分比。DCST 1-AS 1 shRNA可提高巨噬细胞表达M1标志物CD 80和CD 11 c的百分比。然后,我们观察到DCST 1-AS 1的缺失通过灭活NF-κB信号转导抑制OSCC进展。众所周知,NF-κB信号在肿瘤的发展中起着关键作用,我们的研究证明DCST 1-AS 1可以调节NF-κB信号。我们证明,使用拮抗剂阻断NF-κB通路可显著下调由DCST 1-AS 1过表达诱导的OSCC进展和M2巨噬细胞极化。综上所述,DCST 1-AS 1通过调节NF-κB通路在调节OSCC致瘤性和M2巨噬细胞极化中发挥重要作用。
lncRNAs are related to the progression of various diseases, including oral squamous cell carcinoma (OSCC), which is a common squamous cell carcinoma of the head and neck. Tumor-associated macrophages and tumor cells are significant components of tumor microenvironment. M2 polarization of tumor-associated macrophages is a crucial actor in tumor malignancy and metastasis. In this study, we studied the molecular mechanism of lncRNA DCST1-AS1 in OSCC. Here, we reported that DCST1-AS1 was significantly increased in OSCC cells. We found that loss of DCST1-AS1 obviously inhibited the proliferation, migration, and invasion of OSCC cells and xenograft tumor growth. Meanwhile, silencing of DCST1-AS1 also repressed the percentage of macrophages expressing M2 markers CD206 and CD11b. DCST1-AS1 shRNA enhanced the percentage of macrophages expressing M1 markers CD80 and CD11c. Then, we observed that loss of DCST1-AS1 suppressed OSCC progression via inactivating NF-κB signaling. As well established, NF-κB signaling exerts critical roles in tumor progression, and our study proved that DCST1-AS1 could regulate NF-κB signaling. We proved that blocking the NF-κB pathway using antagonists greatly downregulated OSCC progression and M2 macrophage polarization induced by the overexpression of DCST1-AS1. To sum up, we reported that DCST1-AS1 plays an important role in modulating OSCC tumorigenicity and M2 macrophage polarization through regulating the NF-κB pathway.
核因子 - 卡帕布和肿瘤相关的巨噬细胞。
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