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下调 OIP5-AS1 通过抑制 p75NTR 水平影响 proNGF 诱导的胰腺癌转移。

Downregulation of OIP5-AS1 affects proNGF-induced pancreatic cancer metastasis by inhibiting p75NTR levels.

机构信息

Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu 610041, China.

Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu 610041, China.

出版信息

Aging (Albany NY). 2021 Apr 3;13(7):10688-10702. doi: 10.18632/aging.202847.

DOI:10.18632/aging.202847
PMID:33820868
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8064169/
Abstract

We aimed to explore the mechanism by which long non-coding RNA (lncRNA) OIP5-AS1 affects proNGF (precursor nerve growth factor)-induced pancreatic cancer metastasis by targeting the miR-186-5p/NGFR axis. Bioinformatics was used to analyse whether OIP5-AS1 targets miR-186-5p/NGFR and their expression characteristics in pancreatic cancer. OIP5-AS1 and NGFR were overexpressed in pancreatic cancer, and their levels showed a significant positive correlation. Clinical trials also demonstrated that high expression of OIP5-AS1 and NGFR and low expression of miR-186-5p played a pro-cancer role in pancreatic cancer. MiR-186-5p inhibited the migration and invasion of colon cancer cells by targeting NGFR-regulated p75NTR. OIP5-AS1 regulated the action of miR-186-5p on NGFR mRNA and p75NTR by targeting miR-186-5p. Downregulation of NGFR inhibited the expression of p75NTR protein and blocked the role of proNGF in promoting the migration and invasion of pancreatic cancer cells. Animal experiments also showed that the knockdown of miR-186-5p promoted cancer via the expression of NGFR mRNA and p75NTR protein, while the downregulation of proNGF blocked the effects. OIP5-AS1, as a ceRNA, promotes the progression of pancreatic cancer by targeting miR-186-5p/NGFR and affecting the prognosis of patients, which may be related to the action of proNGF.

摘要

我们旨在探索长链非编码 RNA（lncRNA）OIP5-AS1 通过靶向 miR-186-5p/NGFR 轴影响前神经生长因子（proNGF）诱导的胰腺癌转移的机制。使用生物信息学分析 OIP5-AS1 是否靶向 miR-186-5p/NGFR 及其在胰腺癌中的表达特征。在胰腺癌中过表达 OIP5-AS1 和 NGFR，它们的水平呈显著正相关。临床试验还表明，OIP5-AS1 和 NGFR 高表达、miR-186-5p 低表达在胰腺癌中发挥致癌作用。miR-186-5p 通过靶向 NGFR 调节的 p75NTR 抑制结肠癌细胞的迁移和侵袭。OIP5-AS1 通过靶向 miR-186-5p 调节 miR-186-5p 对 NGFR mRNA 和 p75NTR 的作用。下调 NGFR 抑制 p75NTR 蛋白的表达并阻断 proNGF 促进胰腺癌细胞迁移和侵袭的作用。动物实验也表明，miR-186-5p 的敲低通过 NGFR mRNA 和 p75NTR 蛋白的表达促进癌症，而下调 proNGF 则阻断了这种作用。OIP5-AS1 作为 ceRNA 通过靶向 miR-186-5p/NGFR 促进胰腺癌的进展，并影响患者的预后，这可能与 proNGF 的作用有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb54/8064169/57f3cb8d5c24/aging-13-202847-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb54/8064169/db2eb1ba61da/aging-13-202847-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb54/8064169/cb7cb353c741/aging-13-202847-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb54/8064169/57f3cb8d5c24/aging-13-202847-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb54/8064169/db2eb1ba61da/aging-13-202847-g001.jpg
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