中国临床药理学杂志

miR-425-5p靶向成纤维细胞生长因子9对卵巢癌细胞的作用

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蔡怡园 ^1a , 袁泉 ^1a , 张雅秋 ^1b , 钟金妍 ^1a

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(4): 487-491

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (4) : 487 -491

miR-425-5p靶向成纤维细胞生长因子9对卵巢癌细胞的作用

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蔡怡园^1a, 袁泉^1a, 张雅秋^1b, 钟金妍^1a

作者信息

^1a.青岛大学附属青岛市海慈医院（青岛市中医医院），妇科，山东青岛 266033

^1b.青岛大学附属青岛市海慈医院（青岛市中医医院），药剂科，山东青岛 266033

通讯作者:

钟金妍，副主任医师 MP: 13206368236 E-mail: zhongjinyan74@126.com

作者简介:

蔡怡园（1972-），女，副主任医师，主要从事妇科内分泌方面的临床诊疗工作和相关研究

Effects of miR-425-5p targeting fibroblast growth factor 9 on ovarian cancer cells

Yi-yuan CAI^1a, Quan YUAN^1a, Ya-qiu ZHANG^1b, Jin-yan ZHONG^1a

Affiliations

^1a.Department of Gynaecology, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao 266033, Shandong Province, China

^1b.Department of Pharmacy, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao 266033, Shandong Province, China

出版时间: 2025-02-28 doi: 10.13699/j.cnki.1001-6821.2025.04.008

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摘要

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目的

研究微小RNA-425-5p（miR-425-5p）靶向成纤维细胞生长因子9（FGF9）对卵巢癌细胞的增殖、葡萄糖代谢和奥拉帕利耐药性的影响机制。

方法

将人卵巢癌细胞株SKOV3分为对照组（正常培养）、NC inhibitor组（转染空载体miR-NC）、miR-425-5p inhibitor组（转染miR-425-5p抑制剂）、si-NC组（在miR-425-5p inhibitor组的基础上转染si-NC）、si-FGF9组（在miR-425-5p inhibitor组的基础上转染si-FGF9）。用实时定量聚合酶链反应检测miR-425-5p和FGF9 mRNA在细胞中的表达水平，用5-乙炔基-2'-脱氧尿苷（EdU）实验检测细胞增殖率，用乳酸代谢和葡萄糖检测试剂盒检测各组细胞乳酸生成量和葡萄糖吸收量，用细胞计数试剂盒-8实验检测各组细胞的存活率，用蛋白质印迹法检测各组细胞信号传导转录激活因子3/沉默调节蛋白3（STAT3/SITR3）信号通路相关蛋白的表达水平。

结果

NC inhibitor组、miR-425-5p inhibitor组、si-NC组和si-FGF9组的增殖率分别为（84.11±14.76）%、（36.12±6.95）%、（34.32±6.62）%和（77.37±12.83）%，相对乳酸生成量分别为1.02±0.13、0.71±0.09、0.74±0.09和0.89±0.10，相对葡萄糖吸收值分别为0.99±0.14、0.68±0.08、0.70±0.09和0.91±0.11，在40 μmol·L^-1奥拉帕利处理下的存活率分别为（59.86±9.55）%、（41.08±7.72）%、（40.25±7.02）%和（55.71±7.68）%，STAT3蛋白相对表达水平分别为1.01±0.17、0.68±0.10、0.66±0.09和0.88±0.12，SITR3蛋白相对表达水平分别为0.98±0.17、1.84±0.28、1.85±0.29和1.23±0.20。miR-425-5p inhibitor组的上述指标与NC inhibitor组比较，si-FGF9组的上述指标与si-NC组比较，在统计学上差异均有统计学意义（P<0.01，P<0.001）。

结论

沉默miR-425-5p会抑制卵巢癌细胞的增殖和葡萄糖代谢，降低细胞对奥拉帕利的耐药性，可能是通过上调FGF9水平，进而抑制STAT3/SIRT3信号通路来实现的。

关键词

奥拉帕利 / 微小RNA-425-5p / 卵巢癌 / 成纤维细胞生长因子9 / 信号传导转录激活因子3/沉默调节蛋白3 / 葡萄糖代谢

Abstract

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Objective

To investigate the effects of microRNA-425-5p (miR-425-5p) targeting fibroblast growth factor 9 (FGF9) on the proliferation, glucose metabolism and olaparib resistance of ovarian cancer cells.

Methods

Human ovarian cancer cell line SKOV3 were divided into control group (normal culture), NC inhibitor group (transfected empty vector miR-NC), miR-425-5p inhibitor group (transfected miR-425-5p inhibitor), si-NC group (transfected si-NC on the basis of miR-425-5p inhibitor group), si-FGF9 group (transfected si-FGF9 on the basis of miR-425-5p inhibitor group). Quantitative real time polymerase chain reaction was used to detect the expression levels of miR-425-5p and FGF9 in cells. The cell proliferation rate was detected by 5-ethynyl-2′-deoxyuridine (EdU) assay. Lactic acid production and glucose absorption were measured by lactic acid metabolism and glucose detection kit. The survival rate of cells in each group was detected by cell counting kit-8 assay. Western blot was used to detect signal transducer and activator of transcription 3/sirtuin 3 (STAT3/SITR3) signaling pathway related protein expression levels in each group.

Results

The proliferation rate were (84.11±14.76)%, (36.12±6.95)%, (34.32±6.62)% and (77.37±12.83)% in the NC inhibitor group, miR-425-5p inhibitor group, si-NC group and si-FGF9 group, respectively; the relative lactic acid production were 1.02±0.13, 0.71±0.09, 0.74±0.09 and 0.89±0.10, respectively; the relative glucose absorption values were 0.99±0.14, 0.68±0.08, 0.70±0.09 and 0.91±0.11, respectively; the survival rates under 40 μmol·L^-1 olaparib were (59.86±9.55)%, (41.08±7.72)%, (40.25±7.02)% and (55.71±7.68)%, respectively; the relative expression levels of STAT3 protein were 1.01±0.17, 0.68±0.10, 0.66±0.09 and 0.88±0.12, respectively; the relative expression levels of SITR3 protein were 0.98±0.17, 1.84±0.28,1.85±0.29 and 1.23±0.20, respectively. The above indexes of miR-425-5p inhibitor group were compared with those of NC inhibitor group, and those of si-FGF9 group were compared with those of si-NC inhibitor group, and the differences were statistically significant (P<0.01, P<0.001).

Conclusion

Silting miR-425-5p can inhibit the proliferation and glucose metabolism of ovarian cancer cells, and reduce the resistance of cells to olaparib, which may be achieved by up-regulating FGF9 level and inhibiting STAT3/SIRT3 signaling pathway.

Key words

olaparib / microRNA-425-5p / ovarian cancer / fibroblast growth factor 9 / signal transducer and activator of transcription 3/sirtuin 3 / glucose metabolism

引用本文

蔡怡园, 袁泉, 张雅秋, 钟金妍. miR-425-5p靶向成纤维细胞生长因子9对卵巢癌细胞的作用. 中国临床药理学杂志, 2025 , 41 (4) : 487 -491 . DOI: 10.13699/j.cnki.1001-6821.2025.04.008

Yi-yuan CAI, Quan YUAN, Ya-qiu ZHANG, Jin-yan ZHONG. Effects of miR-425-5p targeting fibroblast growth factor 9 on ovarian cancer cells[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (4) : 487 -491 . DOI: 10.13699/j.cnki.1001-6821.2025.04.008

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2025年第41卷第4期

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doi: 10.13699/j.cnki.1001-6821.2025.04.008

接收时间：2024-08-19
首发时间：2026-08-04
出版时间：2025-02-28

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收稿日期：2024-08-19

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作者信息

^1a.青岛大学附属青岛市海慈医院（青岛市中医医院），妇科，山东青岛 266033

^1b.青岛大学附属青岛市海慈医院（青岛市中医医院），药剂科，山东青岛 266033

通讯作者:

钟金妍，副主任医师 MP: 13206368236 E-mail: zhongjinyan74@126.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.04.008

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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