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长链非编码 RNA PROX1 反义 RNA 1 通过与 miR-520d 相互作用促进结直肠癌中 PD-L1 介导的增殖、转移和免疫逃逸。

LncRNA PROX1 antisense RNA 1 promotes PD-L1-mediated proliferation, metastasis, and immune escape in colorectal cancer by interacting with miR-520d.

机构信息

Department of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan.

Department of Anorectal Surgery, Feicheng People's Hospital, Feicheng.

出版信息

Anticancer Drugs. 2023 Jun 1;34(5):669-679. doi: 10.1097/CAD.0000000000001437. Epub 2022 Nov 18.

DOI:10.1097/CAD.0000000000001437
PMID:36730426
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10072212/
Abstract

It was recently found that lncRNA PROX1 antisense RNA 1 (PROX1-AS1) manifested oncogenicity in a variety of malignancies. This work intended to investigate the molecular mechanisms of PROX1-AS1 in colorectal cancer (CRC) development and immune evasion. In this study, both PROX1-AS1 and PD-L1 expressions were lifted in CRC tissues and cells. PROX1-AS1 interference restrained CRC cell proliferation, migration, invasion, as well as CD8 + T-lymphocyte apoptosis, but increased the cytotoxicity and percentage of CD8 + T lymphocytes. The inhibitory effects of PROX1-AS1 inhibition on CRC progression and immune escape were positively related to PD-L1 suppression. PROX1-AS1 absorbed miR-520d to upregulate PD-L1 expression. PROX1-AS1 facilitated CRC progression and immune escape by targeting miR-520d. Furthermore, PROX1-AS1 deletion impaired CRC tumor growth in vivo . To sum up, this study affirmed that PROX1-AS1 could absorb miR-520d to upregulate PD-L1 in CRC, thereby promoting tumor progression and immune escape.

摘要

最近发现，长链非编码 RNA PROX1 反义 RNA 1（PROX1-AS1）在多种恶性肿瘤中表现出致癌性。本研究旨在探讨 PROX1-AS1 在结直肠癌（CRC）发展和免疫逃逸中的分子机制。在这项研究中，CRC 组织和细胞中均升高了 PROX1-AS1 和 PD-L1 的表达。PROX1-AS1 干扰抑制 CRC 细胞增殖、迁移、侵袭以及 CD8+T 淋巴细胞凋亡，但增加了 CD8+T 淋巴细胞的细胞毒性和百分比。PROX1-AS1 抑制对 CRC 进展和免疫逃逸的抑制作用与 PD-L1 抑制呈正相关。PROX1-AS1 吸收 miR-520d 以上调 PD-L1 表达。PROX1-AS1 通过靶向 miR-520d 促进 CRC 进展和免疫逃逸。此外，PROX1-AS1 缺失可损害 CRC 肿瘤在体内的生长。总之，本研究证实 PROX1-AS1 可在 CRC 中吸收 miR-520d 以上调 PD-L1，从而促进肿瘤进展和免疫逃逸。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/414a/10072212/95e3e199c12f/acd-34-669-g007.jpg
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