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LINC01320 通过调节 PURB/DDB2/NEDD4L/TGF-β 轴促进卵巢癌细胞的增殖和迁移。

LINC01320 facilitates cell proliferation and migration of ovarian cancer via regulating PURB/DDB2/NEDD4L/TGF-β axis.

机构信息

State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, 215002, China.

Human Reproductive and Genetic Center, Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.

出版信息

Sci Rep. 2024 Oct 31;14(1):26233. doi: 10.1038/s41598-024-78255-z.

DOI:10.1038/s41598-024-78255-z
PMID:39482389
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11527871/
Abstract

Ovarian cancer (OC) is one of the most prevalent and lethal malignancies affecting the female reproductive system, due to its tendency for metastasis and recurrence. This study identified the overexpression of LINC01320 (or long intergenic nonprotein coding RNA 1320) in tissues of ovarian cancer through the analysis of patient samples and online datasets. In vitro and in vivo experiments demonstrate that silencing of LINC01320 expression led to inhibition of proliferation and metastasis of OC cells. RNA pull-down followed by liquid chromatography tandem mass spectrometry (RNA pull-down-LC-MS/MS) revealed that LINC01320 interacted with purine-rich element binding protein B (PURB), a transcriptional repressor. Furthermore, the RNA-seq analysis identified damage-specific DNA binding protein 2 (DDB2) as a major common target of LINC01320 and PURB. Mechanistically, LINC01320 could recruit PURB to the promoter region of DDB2 to repress DDB2 transcription; thus, promoting the expression of NEDD4L and impeding the TGF-β/SMAD signaling pathway, and ultimately facilitating the progression of OC. Finally, rescue experiments confirmed the involvement of the DDB2/NEDD4L/TGF-β axis in LINC01320-mediated OC progression. In conclusion, this study unveils for the first time the pivotal function of the LINC01320/PURB/DDB2/NEDD4L/TGF-β axis and explores its prospective clinical implications in OC.

摘要

卵巢癌(OC)是一种最常见和致命的影响女性生殖系统的恶性肿瘤,因为它具有转移和复发的倾向。本研究通过对患者样本和在线数据集的分析,发现 LINC01320(或长非编码 RNA 1320)在卵巢癌组织中表达上调。体外和体内实验表明,沉默 LINC01320 的表达会抑制 OC 细胞的增殖和转移。RNA 下拉结合液相色谱串联质谱(RNA pull-down-LC-MS/MS)显示,LINC01320 与嘌呤丰富元件结合蛋白 B(PURB)相互作用,PURB 是一种转录抑制子。此外,RNA-seq 分析鉴定出损伤特异性 DNA 结合蛋白 2(DDB2)是 LINC01320 和 PURB 的主要共同靶标。在机制上,LINC01320 可以募集 PURB 到 DDB2 的启动子区域,从而抑制 DDB2 的转录;因此,促进 NEDD4L 的表达并阻碍 TGF-β/SMAD 信号通路,最终促进 OC 的进展。最后,挽救实验证实了 DDB2/NEDD4L/TGF-β 轴在 LINC01320 介导的 OC 进展中的参与。总之,本研究首次揭示了 LINC01320/PURB/DDB2/NEDD4L/TGF-β 轴的关键作用,并探讨了其在 OC 中的潜在临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/deb7f0ea032b/41598_2024_78255_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/adb713a66dc1/41598_2024_78255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/572f502df998/41598_2024_78255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/65d38c203eb6/41598_2024_78255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/b322b55490b9/41598_2024_78255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/2f3fd5d5d90a/41598_2024_78255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/deb7f0ea032b/41598_2024_78255_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/adb713a66dc1/41598_2024_78255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/572f502df998/41598_2024_78255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/65d38c203eb6/41598_2024_78255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/b322b55490b9/41598_2024_78255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/2f3fd5d5d90a/41598_2024_78255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251b/11527871/deb7f0ea032b/41598_2024_78255_Fig6_HTML.jpg

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