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Bmi-1 通过 RKIP 促进人视网膜母细胞瘤细胞的增殖、迁移和侵袭,抑制细胞凋亡。

Bmi-1 promotes the proliferation, migration and invasion, and inhibits cell apoptosis of human retinoblastoma cells via RKIP.

机构信息

Department of Ophthalmology, The Second People's Hospital of Jinan, No. 148, Jingyi Road, Jinan, 250000, Shandong, China.

出版信息

Sci Rep. 2024 Jun 24;14(1):14544. doi: 10.1038/s41598-024-65011-6.

DOI:10.1038/s41598-024-65011-6
PMID:38914697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11196667/
Abstract

Retinoblastoma is one of the most common ocular malignancies in children. Bmi-1, a member of the Polycomb group family of transcriptional repressors, is expressed in a variety of tumors. The purpose of our study was to explore the role of Bmi-1 in retinoblastoma. RT-qPCR and western blot were used for calculating the mRNA and protein levels of Bmi-1 and RKIP. MTT, Wound healing and Transwell assays were performed to measure the proliferation, migration and invasion in retinoblastoma cells. Cell apoptosis was detected by flow cytometry. The volume and mass of transplanted tumors were detected in nude mice. Bmi-1 was over expressed, and RKIP was low expressed in retinoblastoma cells. Bmi-1 promoted cell proliferation, migration and invasion and suppressed cell apoptosis of Y79 and SO-RB50 cells. Downregulation of Bmi-1 and overexpression of RKIP inhibited cell proliferation, migration and invasion, and increased cell apoptosis. The functions of Bmi-1 knockdown on retinoblastoma cells were blocked by RKIP knockdown, but promoted by RKIP. Down-regulated Bmi-1 inhibited xenograft tumor growth, and RKIP exacerbated this inhibitory effect. Bmi-1 served as a potential therapeutic target for improving the efficacy of clinical treatment in retinoblastoma. All the findings revealed the functions of Bmi-1/RKIP axis in retinoblastoma tumorigenesis.

摘要

视网膜母细胞瘤是儿童最常见的眼部恶性肿瘤之一。Bmi-1 是多梳抑制复合物家族的转录抑制因子成员之一,在多种肿瘤中表达。我们的研究目的是探讨 Bmi-1 在视网膜母细胞瘤中的作用。RT-qPCR 和 Western blot 用于计算 Bmi-1 和 RKIP 的 mRNA 和蛋白水平。MTT、划痕愈合和 Transwell 测定用于测量视网膜母细胞瘤细胞的增殖、迁移和侵袭。流式细胞术检测细胞凋亡。裸鼠检测移植瘤的体积和质量。Bmi-1 在视网膜母细胞瘤细胞中高表达,RKIP 低表达。Bmi-1 促进 Y79 和 SO-RB50 细胞的增殖、迁移和侵袭,抑制细胞凋亡。Bmi-1 下调和 RKIP 过表达抑制细胞增殖、迁移和侵袭,增加细胞凋亡。RKIP 下调阻断了 Bmi-1 对视网膜母细胞瘤细胞的功能,但促进了 RKIP 的作用。下调 Bmi-1 抑制异种移植瘤生长,RKIP 加剧了这种抑制作用。Bmi-1 可能成为改善视网膜母细胞瘤临床治疗效果的潜在治疗靶点。所有发现都揭示了 Bmi-1/RKIP 轴在视网膜母细胞瘤发生中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/a2c460b76f5d/41598_2024_65011_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/9210745ed8d4/41598_2024_65011_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/390ae26ca42f/41598_2024_65011_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/fcffaba595f2/41598_2024_65011_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/910677e05b1f/41598_2024_65011_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/1e5ed1b00125/41598_2024_65011_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/a2c460b76f5d/41598_2024_65011_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/9210745ed8d4/41598_2024_65011_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/390ae26ca42f/41598_2024_65011_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/fcffaba595f2/41598_2024_65011_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/910677e05b1f/41598_2024_65011_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/1e5ed1b00125/41598_2024_65011_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26f/11196667/a2c460b76f5d/41598_2024_65011_Fig6_HTML.jpg

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