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LncRNA FAM225B 通过调节转录因子 DDX17 调控 PDIA4 介导的卵巢癌细胞侵袭和迁移。

LncRNA FAM225B Regulates PDIA4-Mediated Ovarian Cancer Cell Invasion and Migration via Modulating Transcription Factor DDX17.

机构信息

No. 2 Obstetrics and Gynecology Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.

Obstetrics and Gynecology Department, Hunan Provincial People's Hospital Xingsha Branch (People's Hospital of Changsha County), Changsha, China.

出版信息

Breast J. 2023 Sep 7;2023:3970444. doi: 10.1155/2023/3970444. eCollection 2023.

DOI:10.1155/2023/3970444
PMID:37720188
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10501846/
Abstract

OBJECTIVE

This study aimed to explore the roles and mechanisms of lncRNA FAM225B and PDIA4 in ovarian cancer.

METHODS

RT-qPCR and Western blot assays were performed to detect the expression levels of the lncRNAs FAM225B, DDX17, and PDIA4 in the serum of patients with ovarian cancer and cell lines. Cells were transfected with lncRNA FAM225B- and PDIA4-related vectors to determine the malignant phenotypes using functional experiments. The mutual binding of lncRNA FAM225B and DDX17 was verified using RNA pull-down and RIP assays.

RESULTS

The expression of lncRNAs FAM225B and PDIA4 was decreased in the serum of patients with ovarian cancer and cell lines. Restoration of lncRNA FAM225B or PDIA4 reduced cell proliferation, migration, and invasion abilities and elevated the apoptosis rate, whereas suppression of lncRNA FAM225B or PDIA4 exhibited an inverse trend. RNA pull-down and RIP assays revealed a direct interaction between lncRNA FAM225B and DDX17. ChIP assay revealed a relationship between DDX17 and the PDIA4 promoter. LncRNA FAM225B and DDX17 positively regulate PDIA4 expression. Downregulation of PDIA4 expression counteracts the suppressive effect of lncRNA FAM225B overexpression in ovarian cancer cells.

CONCLUSION

This research study supports the fact that lncRNA FAM225B in ovarian cancer can upregulate PDIA4 by directly binding to DDX17, inhibiting the activities of ovarian cancer cells.

摘要

目的

本研究旨在探讨 lncRNA FAM225B 和 PDIA4 在卵巢癌中的作用和机制。

方法

通过 RT-qPCR 和 Western blot 检测卵巢癌患者血清和细胞系中 lncRNA FAM225B、DDX17 和 PDIA4 的表达水平。通过转染 lncRNA FAM225B 和 PDIA4 相关载体的功能实验，确定细胞的恶性表型。采用 RNA 下拉和 RIP 实验验证 lncRNA FAM225B 和 DDX17 之间的相互结合。

结果

lncRNA FAM225B 和 PDIA4 的表达在卵巢癌患者血清和细胞系中降低。恢复 lncRNA FAM225B 或 PDIA4 降低了细胞增殖、迁移和侵袭能力，提高了细胞凋亡率，而抑制 lncRNA FAM225B 或 PDIA4 则表现出相反的趋势。RNA 下拉和 RIP 实验显示 lncRNA FAM225B 与 DDX17 之间存在直接相互作用。ChIP 实验显示 DDX17 与 PDIA4 启动子之间存在关系。lncRNA FAM225B 和 DDX17 正向调节 PDIA4 的表达。下调 PDIA4 表达可拮抗 lncRNA FAM225B 过表达对卵巢癌细胞的抑制作用。

结论

本研究表明，lncRNA FAM225B 在卵巢癌中可通过直接结合 DDX17 而上调 PDIA4，抑制卵巢癌细胞的活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/ddb06d344f57/TBJ2023-3970444.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/dcc36406f85c/TBJ2023-3970444.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/7fb061d494af/TBJ2023-3970444.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/9a6934739108/TBJ2023-3970444.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/37bb5cf1d96c/TBJ2023-3970444.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/ddb06d344f57/TBJ2023-3970444.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/dcc36406f85c/TBJ2023-3970444.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/7fb061d494af/TBJ2023-3970444.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/9a6934739108/TBJ2023-3970444.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/37bb5cf1d96c/TBJ2023-3970444.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9f/10501846/ddb06d344f57/TBJ2023-3970444.005.jpg

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