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牙龈卟啉单胞菌外膜囊泡包裹的 sRNA23392 通过靶向桥粒蛋白-2 促进口腔鳞状细胞癌迁移和侵袭。

sRNA23392 packaged by Porphyromonas gingivalis outer membrane vesicles promotes oral squamous cell carcinomas migration and invasion by targeting desmocollin-2.

机构信息

Department of Emergency and Oral Medicine, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, China.

Department of Dental Materials, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, China.

出版信息

Mol Oral Microbiol. 2021 Jun;36(3):182-191. doi: 10.1111/omi.12334. Epub 2021 Apr 4.

DOI:10.1111/omi.12334
PMID:33764008
Abstract

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignant tumor. Periodontitis, a common chronic inflammatory disease, has been proven to increase the risk of oral cancers. Porphyromonas gingivalis (P. gingivalis), the major pathogen in periodontal disease, was recently shown to promote the development of OSCC. However, the underlying mechanisms have not been defined. Emerging evidence suggests that P. gingivalis outer membrane vesicles (OMVs) contain different packaged small RNAs (sRNAs) with the potential to target host mRNA function and/or stability. In this study, we found that P. gingivalis OMVs promote the invasion and migration of OSCC cells in vitro. Further research showed that sRNA23392 was abundant in P. gingivalis OMVs and it promoted the invasion and migration of OSCC cells by targeting desmocollin-2 (DSC2). DSC2, a desmosomal cadherin family member, has been found to be involved in tumor progression. sRNA23392 inhibitors attenuated P. gingivalis OMV-induced migration and invasion of OSCC cells. Collectively, these findings are consistent with the hypothesis that sRNA23392 in P. gingivalis OMVs is a novel mechanism of the host-pathogen interaction, whereby P. gingivalis promotes the invasion and migration of OSCC.

摘要

口腔鳞状细胞癌(OSCC)是最常见的头颈部恶性肿瘤。牙周炎是一种常见的慢性炎症性疾病,已被证明会增加口腔癌的风险。牙龈卟啉单胞菌(P. gingivalis)是牙周病的主要病原体,最近被证明可促进 OSCC 的发展。然而,其潜在机制尚未确定。新出现的证据表明,牙龈卟啉单胞菌外膜囊泡(OMVs)含有不同包装的小 RNA(sRNA),具有靶向宿主 mRNA 功能和/或稳定性的潜力。在这项研究中,我们发现 P. gingivalis OMVs 可促进 OSCC 细胞在体外的侵袭和迁移。进一步的研究表明,sRNA23392 在 P. gingivalis OMVs 中含量丰富,它通过靶向桥粒芯糖蛋白 2(DSC2)促进 OSCC 细胞的侵袭和迁移。桥粒芯糖蛋白 2 是桥粒黏附分子家族的一员,已被发现参与肿瘤进展。sRNA23392 抑制剂减弱了 P. gingivalis OMV 诱导的 OSCC 细胞迁移和侵袭。总的来说,这些发现与以下假设一致,即 P. gingivalis OMV 中的 sRNA23392 是宿主-病原体相互作用的一种新机制,通过该机制,P. gingivalis 促进了 OSCC 的侵袭和迁移。

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