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环状 RNA 相互作用蛋白激酶 3 通过微小 RNA-7 调节血管内皮生长因子影响卵巢癌细胞增殖和凋亡。

CircHIPK3 modulates VEGF through MiR-7 to affect ovarian cancer cell proliferation and apoptosis.

机构信息

Department of Gynecology, Taizhou Hospital, #150 Ximen Ave, Linhai, Zhejiang 317000, China.

出版信息

J BUON. 2021 May-Jun;26(3):691-697.

PMID:34268922
Abstract

PURPOSE

The purpose of this study was to observe the effects of circHIPK3on the proliferation and apoptosis of ovarian cancer cells, and to further explore the potential mechanism therein.

METHODS

CircHIPK3 was determined in the carcinoma tissues, normal adjacent tissues, and also in ovarian cancer cells via RT-PCR. The proliferation and apoptosis of cells were observed via colony-forming assay, 5-ethynyl-2'-deoxyuridine (EdU) staining and Western blotting. Moreover, the effect of the inhibition of circHIPK3 on the in vivo growth of ovarian cancer cells was detected using subcutaneous tumorigenesis assay. Finally, the effect of circHIPK3 on the expression of the micro ribonucleic acid (miR)-7/vascular endothelial growth factor (VEGF) signaling pathway in ovarian cancer cells was examined.

RESULTS

CircHIPK3 in the carcinoma tissues was obviously higher than that in normal adjacent tissues. SKOV3 cell lines transfected with circHIPK3 inhibitor exhibited declined number of colonies. The inhibition of circHIPK3 distinctly suppressed the expression of B-cell lymphoma 2 (Bcl-2) and raised that of Bcl-2 associated X protein (Bax). Besides, the inhibition of circHIPK3 obviously weakened the tumorigenicity of ovarian cancer cells subcutaneously transplanted. Finally, it was found that miR-7 declined obviously and VEGF rose distinctly in the carcinoma tissues, and the in vitro assay verified the obvious increase in the expression of miR-7 and the prominently inhibited VEGF protein expression in the ovarian cancer cells with the inhibition of circHIPK3.

CONCLUSIONS

CircHIPK3 has an obviously increased expression level in the carcinoma tissues of ovarian cancer patients, and the inhibition of circHIPK3 can activate the miR-7-mediated decline in the expression of VEGF to repress the proliferation and promote the apoptosis of ovarian cancer cells.

摘要

目的

本研究旨在观察环状 RNA 结合蛋白激酶 3(circHIPK3)对卵巢癌细胞增殖和凋亡的影响,并进一步探讨其潜在机制。

方法

采用 RT-PCR 检测癌组织、癌旁正常组织和卵巢癌细胞中的 circHIPK3。通过集落形成实验、5-乙炔基-2'-脱氧尿苷(EdU)染色和 Western blot 检测细胞的增殖和凋亡。此外,通过皮下肿瘤生成实验检测抑制 circHIPK3 对卵巢癌细胞体内生长的影响。最后,检测 circHIPK3 对卵巢癌细胞中微小 RNA(miR)-7/血管内皮生长因子(VEGF)信号通路表达的影响。

结果

癌组织中的 circHIPK3 明显高于癌旁正常组织。转染 circHIPK3 抑制剂的 SKOV3 细胞系的集落数减少。抑制 circHIPK3 明显抑制 B 细胞淋巴瘤 2(Bcl-2)的表达,提高 Bcl-2 相关 X 蛋白(Bax)的表达。此外,抑制 circHIPK3 明显减弱了卵巢癌细胞皮下移植的致瘤性。最后,发现 miR-7 在癌组织中明显下降,VEGF 明显升高,体外实验证实抑制 circHIPK3 后卵巢癌细胞中 miR-7 的表达明显增加,VEGF 蛋白表达明显受到抑制。

结论

circHIPK3 在卵巢癌患者的癌组织中表达水平明显升高,抑制 circHIPK3 可激活 miR-7 介导的 VEGF 表达下调,抑制卵巢癌细胞增殖,促进其凋亡。

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