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靶向 lncRNA FGD5-AS1/miR-497-5p/PD-L1 轴抑制结直肠癌(CC)中的恶性表型。

Targeting the lncRNA FGD5-AS1/miR-497-5p/PD-L1 Axis Inhibits Malignant Phenotypes in Colon Cancer (CC).

机构信息

The Department of Pathology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunzhou Road No. 519, Kunming City, 650100 Yunnan Province, China.

The Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunzhou Road No. 519, Kunming City, 650100 Yunnan Province, China.

出版信息

Biomed Res Int. 2022 Jul 6;2022:1133332. doi: 10.1155/2022/1133332. eCollection 2022.

DOI:10.1155/2022/1133332
PMID:35845947
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9279048/
Abstract

Long noncoding RNAs (lncRNAs) regulate cancer progression and drug resistance. However, the role of lncRNA FGD5-AS1 in regulating colon cancer (CC) progression is still largely unknown. Hence, this study investigated the role of lncRNA FGD5-AS1 in regulating colon cancer (CC) progression and found that lncRNA FGD5-AS1 regulated miR-497-5p/PD-L1 axis to promote cancer progression in CC cells and . Specifically, we found that lncRNA FGD5-AS1 and PD-L1 tended to be high-expressed, while miR-497-5p was low-expressed in CC tissues and cell lines compared to the normal adjacent tissues and cells. Next, we found that lncRNA FGD5-AS1 positively regulated PD-L1 in CC cells by sponging miR-497-5p. Finally, our gain- and loss-of-function experiments evidenced that the lncRNA FGD5-AS1/miR-497-5p/PD-L1 axis regulates CC progression. Functionally, the data suggested that lncRNA FGD5-AS1 positively regulated while miR-497-5p negatively modulated malignant phenotypes, including cell proliferation, viability, invasion, migration, epithelial-mesenchymal transition (EMT), and tumorigenesis in CC cells. Interestingly, the inhibiting effects of lncRNA FGD5-AS1 ablation on CC development were abrogated by both silencing miR-497-5p and upregulating PD-L1. This study found that lncRNA FGD5-AS1 sponged miR-497-5p to upregulate PD-L1, resulting in CC progression, and provided novel agents for CC diagnosis and prognosis.

摘要

长链非编码 RNA(lncRNA)调节癌症的发生和耐药性。然而,lncRNA FGD5-AS1 在调节结肠癌(CC)进展中的作用在很大程度上仍然未知。因此,本研究探讨了 lncRNA FGD5-AS1 在调节结肠癌(CC)进展中的作用,发现 lncRNA FGD5-AS1 通过调节 miR-497-5p/PD-L1 轴促进 CC 细胞的癌症进展。具体来说,我们发现与正常相邻组织和细胞相比,lncRNA FGD5-AS1 和 PD-L1 在 CC 组织和细胞系中倾向于高表达,而 miR-497-5p 则低表达。接下来,我们发现 lncRNA FGD5-AS1 通过海绵 miR-497-5p 正向调节 CC 细胞中的 PD-L1。最后,我们的增益和缺失功能实验证明了 lncRNA FGD5-AS1/miR-497-5p/PD-L1 轴调节 CC 进展。功能上,数据表明 lncRNA FGD5-AS1 正向调节而 miR-497-5p 负调节 CC 细胞中的恶性表型,包括细胞增殖、活力、侵袭、迁移、上皮-间充质转化(EMT)和肿瘤发生。有趣的是,沉默 miR-497-5p 和上调 PD-L1 均可消除 lncRNA FGD5-AS1 缺失对 CC 发展的抑制作用。本研究发现 lncRNA FGD5-AS1 通过海绵 miR-497-5p 上调 PD-L1,导致 CC 进展,并为 CC 的诊断和预后提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/05a916672d47/BMRI2022-1133332.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/41ec24d3ed27/BMRI2022-1133332.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/cbe9765df260/BMRI2022-1133332.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/9d1d23d40837/BMRI2022-1133332.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/b9d24560993e/BMRI2022-1133332.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/05a916672d47/BMRI2022-1133332.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/41ec24d3ed27/BMRI2022-1133332.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/cbe9765df260/BMRI2022-1133332.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/9d1d23d40837/BMRI2022-1133332.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/b9d24560993e/BMRI2022-1133332.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee00/9279048/05a916672d47/BMRI2022-1133332.005.jpg

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