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环状 SMARCA5 通过与 SND1 相互作用并下调宫颈癌中的 YWHAB 基因抑制肿瘤转移。

Circ SMARCA5 Inhibited Tumor Metastasis by Interacting with SND1 and Downregulating the YWHAB Gene in Cervical Cancer.

机构信息

Department of Gynaecology and Obstetrics, 569063the Second Affiliated Hospital of Zhengzhou University, Henan Province, China.

出版信息

Cell Transplant. 2021 Jan-Dec;30:963689720983786. doi: 10.1177/0963689720983786.

DOI:10.1177/0963689720983786
PMID:33588586
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7894587/
Abstract

Cervical cancer is one of the diseases that seriously endanger women's health. Circular RNA plays an important role in regulating the occurrence and development of cervical cancer. Here, we investigated the mechanisms of circ SMARCA5 in the development of cervical cancer. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) results showed that the expression of SMARCA5 was downregulated in cervical cancer tissues and cell lines. Then we found that overexpression of SMARCA5 inhibited proliferation and invasion, but promoted apoptosis in cervical cancer cells. These were detected by Cell Counting Kit-8, Transwell, and Annexin V-fluorescein isothiocyanate/propidium iodide detection kit, respectively, and the expression of the apoptosis-related proteins was determined by western blotting. Then we predicted that SMARCA5 combined with Staphylococcal nuclease domain-containing 1 (SND1) by starBase, and verified by RNA pull-down assay. To further reveal the molecular mechanisms of SMARCA5 in the progression of cervical cancer, the interaction protein of SND1 was predicted by STRING, and the interaction was verified by co-immunoprecipitation assay. Then, the effects of SND1 or YWHAB on the development of cervical cancer were detected by the gain and loss function test, and we found that knockdown of SND1 or YWHAB reversed the effects of SMARCA5 short interfering RNA on proliferation, invasion, and apoptosis of cervical cancer cells. Overexpression of SMARCA5 inhibited cervical cancer metastasis . Our results showed that overexpression of circ SMARCA5 inhibits the binding of SND1 to YWHAB, and inhibits the proliferation and invasion, but promotes apoptosis in cervical cancer cells, thus inhibiting the metastasis of cervical cancer.

摘要

宫颈癌是严重危害女性健康的疾病之一。环状 RNA 在调控宫颈癌的发生发展中起重要作用。在这里,我们研究了 circSMARCA5 在宫颈癌发展中的作用机制。定量逆转录聚合酶链反应(RT-qPCR)结果显示,SMARCA5 在宫颈癌组织和细胞系中的表达下调。然后我们发现,SMARCA5 的过表达抑制了宫颈癌细胞的增殖和侵袭,但促进了细胞凋亡。这些分别通过细胞计数试剂盒-8、Transwell 和 Annexin V-荧光素异硫氰酸酯/碘化丙啶检测试剂盒检测,通过蛋白质印迹法检测凋亡相关蛋白的表达。然后我们通过 starBase 预测 SMARCA5 与含葡萄球菌核酸酶结构域蛋白 1(SND1)结合,并通过 RNA 下拉实验验证。为了进一步揭示 SMARCA5 在宫颈癌进展中的分子机制,通过 STRING 预测 SND1 的相互作用蛋白,并通过 co-immunoprecipitation 实验验证相互作用。然后,通过增益和缺失功能试验检测 SND1 或 YWHAB 对宫颈癌发展的影响,我们发现 SND1 或 YWHAB 的敲低逆转了 SMARCA5 小干扰 RNA 对宫颈癌细胞增殖、侵袭和凋亡的影响。SMARCA5 的过表达抑制了宫颈癌的转移。我们的结果表明,circSMARCA5 的过表达抑制了 SND1 与 YWHAB 的结合,抑制了宫颈癌细胞的增殖和侵袭,但促进了细胞凋亡,从而抑制了宫颈癌的转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/ec56f4ae0318/10.1177_0963689720983786-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/00a687de29bf/10.1177_0963689720983786-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/098e380fc49c/10.1177_0963689720983786-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/6411a4ea8917/10.1177_0963689720983786-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/2866110800c7/10.1177_0963689720983786-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/2f49b987e129/10.1177_0963689720983786-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/df8c801f8e4f/10.1177_0963689720983786-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/ab4aa750c3d7/10.1177_0963689720983786-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/ec56f4ae0318/10.1177_0963689720983786-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/00a687de29bf/10.1177_0963689720983786-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/098e380fc49c/10.1177_0963689720983786-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/6411a4ea8917/10.1177_0963689720983786-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/2866110800c7/10.1177_0963689720983786-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/2f49b987e129/10.1177_0963689720983786-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/df8c801f8e4f/10.1177_0963689720983786-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/ab4aa750c3d7/10.1177_0963689720983786-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96a0/7894587/ec56f4ae0318/10.1177_0963689720983786-fig8.jpg

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