UHRF1在三阴乳腺癌细胞中的表达及增殖侵袭的影响

doi:10.3969/j.issn.1006-6233.2021.05.01

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摘要 目的: 研究UHRF1在三阴性乳腺癌(TNBC)乳腺组织及其细胞系中表达及对其癌细胞增殖和侵袭的影响。方法: 采用免疫组化检测非TNBC和TNBC患者乳腺组织UHRF1表达;采用免疫荧光检测非TNBC和TNBC患者乳腺组织Ki67和UHRF1定位表达;qRT-PCR和Western blot检测未转化的人类乳腺上皮细胞(MCF-10A)、雌激素和孕激素受体(ER+ / PR+)乳腺癌细胞系(MCF-7)和TNBC乳腺癌细胞系(MDA-MB-231和MDA-MB-436)中UHRF1 mRNA和蛋白表达;采用UHRF1-shRNA慢病毒转导TNBC细胞系(MDA-MB-231和MDA-MB-436)并构建UHRF1敲低(Knock down,UHRF1 KD)细胞系;采用Ki67染色和CCK-8检测WT和UHRF1 KD细胞增殖和活力变化;采用Transwell检测WT和UHRF1 KD细胞侵袭变化;采用qPCR检测FOXO4、PPARG、P53和 P21 mRNA表达。结果: TNBC患者乳腺组织中UHRF1的表达明显高于非TNBC患者(P<0.001);TNBC患者乳腺组织中UHRF1+Ki67+/Ki67+细胞比例明显高于非TNBC患者(P<0.05);TNBC细胞系(MDA-MB-231和MDA-MB-436)中UHRF1 mRNA和蛋白表达明显高于人类乳腺上皮细胞(MCF-10A)和雌激素和孕激素受体(ER+/PR+)乳腺癌细胞系(MCF-7)(P<0.05);与WT的TNBC细胞系(MDA-MB-231和MDA-MB-436)相比,UHRF1 KD的TNBC细胞系(MDA-MB-231和MDA-MB-436)细胞增殖、活力和侵袭能力明显降低(P<0.05);UHRF1 KD的TNBC细胞系(MDA-MB-231和MDA-MB-436)中BRAC1、PPARG、P53和P21 mRNA表达明显低于WT的TNBC细胞系(P<0.05),P16和FOXO4 mRNA表达无统计学差异(P>0.05)。结论: UHRF1高表达于TNBC乳腺组织和细胞系,且下调UHRF1可抑制TNBC细胞增殖和侵袭,并与抑制PPAR-γ BRAC1/P53/P21信号有关。

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	袁惠玲
	吴丽华
	陈桂林
	黄珂铭

关键词 ：三阴性乳腺癌, UHRF1, 细胞增殖, 侵袭

Abstract：Objective: To study the expression of UHRF1 in triple negative breast cancer (TNBC) breast tissue and its cell line and its effect on cancer cell proliferation and invasion. Methods: Immunohistochemistry was used to detect the expression of UHRF1 in breast tissues of non-TNBC and TNBC patients; immunofluorescence was used to detect the localized expression of Ki67 and UHRF1 in breast tissues of non-TNBC and TNBC patients; qRT-PCR and Western blot were used to detect untransformed human breast epithelial cells (MCF-10A), estrogen and progesterone receptor (ER+ / PR+) breast cancer cell lines (MCF-7) and TNBC breast cancer cell lines (MDA-MB-231 and MDA-MB-436) UHRF1 mRNA and protein expression ;UHRF1-shRNA lentivirus was used to transduce TNBC cell lines (MDA-MB-231 and MDA-MB-436) and the UHRF1 knock down (Knock down, UHRF1 KD) cell line was constructed; Ki67 staining and CCK-8 were used to detect WT and UHRF1 KD cell proliferation and viability changes; Transwell was used to detect WT and UHRF1 KD cell invasion changes; qPCR was used to detect the expression of FOXO4, PPARG, P53 and P21 mRNA. Results: The expression of UHRF1 in breast tissue of TNBC patients was significantly higher than that in non-TNBC patients (P<0.05); the ratio of UHRF1+Ki67+/Ki67+ cells in breast tissue of TNBC patients was significantly higher than that in non-TNBC patients (P<0.05); TNBC cell line ( MDA-MB-231 and MDA-MB-436) UHRF1 mRNA and protein expression were significantly higher than human breast epithelial cells (MCF-10A) and estrogen and progesterone receptor (ER+ / PR+) breast cancer cell lines (MCF- 7) (P<0.05); compared with WT's TNBC cell line (MDA-MB-231 and MDA-MB-436), UHRF1 KD's TNBC cell line (MDA-MB-231 and MDA-MB-436) cells Proliferation, vitality and invasion ability were significantly reduced (P<0.05); UHRF1 KD TNBC cell lines (MDA-MB-231 and MDA-MB-436) FOXO4, PPARG, P53 and P21 mRNA expression were significantly reduced (P<0.05) . Conclusion: UHRF1 is highly expressed in TNBC breast tissues and cell lines, and down-regulation of UHRF1 can inhibit the proliferation and invasion of TNBC cells, which is related to the inhibition of FOXO4/P53 and PPARG/P21 signaling pathways.

Key words： Triple-negative breast cancer UHRF1 Cell proliferation Invasion

基金资助:国家自然科学基金,(编号:81802625);广东省东莞市科技发展重点项目,(编号:2018507150011656)

引用本文:

袁惠玲, 吴丽华, 陈桂林, 黄珂铭. UHRF1在三阴乳腺癌细胞中的表达及增殖侵袭的影响[J]. 河北医学, 2021, 27(5): 705-710.
YUAN Huiling, WU Lihua, CHEN Guilin, et al. Expression of UHRF1 in Triple-negative Breast Cancer Cells and Its Effect on Proliferation and Invasion. HeBei Med, 2021, 27(5): 705-710.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2021.05.01 或 http://www.hbyxzzs.cn/CN/Y2021/V27/I5/705

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