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hsa-miR-429 靶向 CBX8 促进弥漫大 B 细胞淋巴瘤细胞凋亡。

hsa‑miR‑429 targets CBX8 to promote cell apoptosis in diffuse large B‑cell lymphoma.

机构信息

Department of Hematology, Jingzhou Central Hospital, Institute of Hematology, Yangtze University, Jingzhou, Hubei 434020, P.R. China.

出版信息

Mol Med Rep. 2021 Dec;24(6). doi: 10.3892/mmr.2021.12497. Epub 2021 Oct 15.

DOI:10.3892/mmr.2021.12497
PMID:34651663
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8548936/
Abstract

Diffuse large B‑cell lymphoma (DLBCL) is the most common type of non‑Hodgkin lymphoma worldwide. Several studies have indicated that (hsa)‑microRNA (miR)‑429 exerts a tumor‑suppressive effect on a variety of malignant tumors. To the best of our knowledge, the molecular function and mechanism of action of hsa‑miR‑429 in DLBCL have not been evaluated to date. The present study demonstrated that the expression of hsa‑miR‑429 in DLBCL cells was significantly reduced. hsa‑miR‑429 inhibited the proliferation of the DLBCL cell lines, SUDHL‑4 and DB, and promoted apoptosis. A dual luciferase reporter assay was used to demonstrate that chromobox 8 (CBX8) was the target gene of hsa‑miR‑429. Overexpression of CBX8 promoted the proliferation of SUDHL‑4 and DB cells and inhibited apoptosis, thereby playing a cancer‑promoting role. Transfection of hsa‑miR‑429 mimic into DB cells overexpressing CBX8 antagonized the effect of CBX8 on the proliferation of DB cells. Moreover, the apoptotic rate was increased in DB cells overexpressing CBX8 and transfected with hsa‑miR‑429 mimic, while the proportion of cells in the G/M phase was significantly reduced. These results demonstrated the antagonistic effect of hsa‑miR‑429 on the oncogenic function of CBX8. Therefore, in DLBCL, the tumor suppressor effect of hsa‑miR‑429 may be achieved by targeted downregulation of CBX8, suggesting that hsa‑miR‑429 may be used as a diagnostic marker and a potential nucleic acid drug for DLBCL. CBX8 may also represent an effective therapeutic target for DLBCL.

摘要

弥漫性大 B 细胞淋巴瘤(DLBCL)是全球最常见的非霍奇金淋巴瘤类型。有几项研究表明,(hsa)-微小 RNA(miR)-429 对多种恶性肿瘤具有肿瘤抑制作用。据我们所知,hsa-miR-429 在 DLBCL 中的分子功能和作用机制尚未得到评估。本研究表明,DLBCL 细胞中 hsa-miR-429 的表达显著降低。hsa-miR-429 抑制了 DLBCL 细胞系 SUDHL-4 和 DB 的增殖,并促进了细胞凋亡。双荧光素酶报告基因检测证实 CBX8 是 hsa-miR-429 的靶基因。过表达 CBX8 促进了 SUDHL-4 和 DB 细胞的增殖并抑制了细胞凋亡,从而发挥了促进癌症的作用。将 hsa-miR-429 模拟物转染至过表达 CBX8 的 DB 细胞中,拮抗了 CBX8 对 DB 细胞增殖的影响。此外,过表达 CBX8 并转染 hsa-miR-429 模拟物的 DB 细胞的凋亡率增加,而 G/M 期细胞的比例显著降低。这些结果表明 hsa-miR-429 对 CBX8 的致癌功能具有拮抗作用。因此,在 DLBCL 中,hsa-miR-429 通过靶向下调 CBX8 发挥肿瘤抑制作用,表明 hsa-miR-429 可作为诊断标志物和用于治疗 DLBCL 的潜在核酸药物。CBX8 也可能成为 DLBCL 的有效治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/4568b8b1739b/mmr-24-06-12497-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/bf2f0ab066ca/mmr-24-06-12497-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/76cd129daa14/mmr-24-06-12497-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/3610ec3a5e27/mmr-24-06-12497-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/217318ee476b/mmr-24-06-12497-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/4568b8b1739b/mmr-24-06-12497-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/bf2f0ab066ca/mmr-24-06-12497-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/76cd129daa14/mmr-24-06-12497-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/3610ec3a5e27/mmr-24-06-12497-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/217318ee476b/mmr-24-06-12497-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b293/8548936/4568b8b1739b/mmr-24-06-12497-g04.jpg

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