Chromatin remodeling protein MORC2 promotes a breast cancer stem-like phenotype by regulating ALDH1A3 expression

张　飒; 许佳慧; 柳素玲

doi:10.19401/j.cnki.1007-3639.2017.03.001

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Chromatin remodeling protein MORC2 promotes a breast cancer stem-like phenotype by regulating ALDH1A3 expression

更新时间：2025-12-31

- Chromatin remodeling protein MORC2 promotes a breast cancer stem-like phenotype by regulating ALDH1A3 expression
- China Oncology Vol. 27, Issue 3, Pages: 161-168(2017)
- 作者机构：
  
  复旦大学生物医学研究院及肿瘤研究所,上海,200032
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2017.03.001
  CLC：
- Published Online：12 April 2017，
  
  Published：12 April 2017
- 稿件说明：
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张　飒,许佳慧,柳素玲,等. 染色质重塑蛋白MORC2通过调节ALDH1A3表达促进乳腺癌细胞的干性[J]. 中国癌症杂志, 2017, 27(3): 161-168.

张　飒, 许佳慧, 柳素玲. Chromatin remodeling protein MORC2 promotes a breast cancer stem-like phenotype by regulating ALDH1A3 expression[J]. China Oncology, 2017, 27(3): 161-168.
张　飒,许佳慧,柳素玲,等. 染色质重塑蛋白MORC2通过调节ALDH1A3表达促进乳腺癌细胞的干性[J]. 中国癌症杂志, 2017, 27(3): 161-168. DOI： 10.19401/j.cnki.1007-3639.2017.03.001.

张　飒, 许佳慧, 柳素玲. Chromatin remodeling protein MORC2 promotes a breast cancer stem-like phenotype by regulating ALDH1A3 expression[J]. China Oncology, 2017, 27(3): 161-168. DOI： 10.19401/j.cnki.1007-3639.2017.03.001.

摘要

背景与目的：染色质重塑蛋白MORC家族CW型锌指结构蛋白2(microrchidia family CW-type zinc finger 2

MORC2)在DNA介导的基因转录及DNA损伤修复等基本生物学过程中发挥重要作用，但其对乳腺癌细胞生物学行为的影响目前尚无相关报道。乙醛脱氢酶(aldehyde dehydrogenase，ALDH)家族成员ALDH1A3(aldehyde dehydrogenase family 1 member A3，ALDH1A3)是一种公认的乳腺癌干细胞的标志物，但其在乳腺癌细胞中的调控机制目前尚不清楚。该研究拟探讨敲低MORC2基因对ALDH1A3表达以及对乳腺癌细胞干性的影响。方法：利用短发夹RNA (short hairpin RNA，shRNA) 介导的基因沉默方法构建稳定敲低MORC2基因的乳腺癌细胞系；利用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction，RTFQ-PCR)和蛋白［质］印迹法(Western blot)分析敲低MORC2基因对ALDH1A3表达的影响；利用微球体形成实验和流式细胞荧光分选技术(fluorescence activated cell sorting

FACS)分析敲低MORC2对乳腺癌干细胞亚群的影响。结果：Western blot和RTFQ-PCR分析结果显示，敲低MORC2基因显著下调ALDH1A3蛋白及mRNA水平；微球体形成实验显示敲低MORC2基因显著抑制MCF-7细胞的成球能力；FACS分析显示敲低MORC2基因显著下调ALDH1A3阳性乳腺癌干细胞亚群

而对CD44

CD24

乳腺癌干细胞亚群没有明显影响。结论：MORC2通过调节ALDH1A3的表达促进乳腺癌干细胞表型。

Abstract

Background and purpose: MORC2 (microrchidia family CW-type zinc finger 2

MORC2) is a newly identified chromatin remodeling protein that plays key roles in DNA-based biological processes including gene transcription and DNA damage repair. However

its functional role in breast cancer development and progression remains unknown. ALDH1A3 (aldehyde dehydrogenase 1 family

member A3)

a member of the aldehyde dehydrogenases (ALDH) superfamily

is a putative breast cancer stem cell marker

but its regulatory mechanism in breast cancer is poorly characterized. This study aimed to investigate the effects of knockdown of endogenous MORC2 on the expression levels of ALDH1A3 and the breast cancer stem-like phenotype in MCF-7 cells. Methods: Human breast cancer MCF-7 cells were infected with negative control short hairpin RNAs (shNC) and specific shRNAs targeting human MORC2 (shMORC2)

followed by selection with puromycin to generate stable MORC2 gene knockdown cell lines. Western blot and real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) were used to examine the protein and mRNA levels of ALDH1A3 in MCF-7 cells stably expressing shNC and shMORC2. Microsphere formation and fluorescence-activated cell sorting (FACS) assays were used to analyze the effects of knockdown of MORC2 on the breast cancer stem-like phenotype. Results: Western blot and RTFQ-PCR analyses revealed that the protein and mRNA levels of ALDH1A3 were significantly down-regulated in shMORC2 expressing cells as compared with shNC -transfected control cells. Moreover

mammosphere formation assay showed that knockdown of endogenous MORC2 in MCF-7 cells significantly reduced the ability of cells to form microspheres. Consistently

FACS assays demonstrated that shMORC2-transfected cells had a lower proportion of ALDH-positive stem cells as compared with shNC expressing cells. In contrast

knockdown of MORC2 did not significantly affect the CD44

CD24

stem cell population. Conclusion: MORC2 promotes a breast cancer stem-like phenotype through

at least in part

regulating ALDH1A3 expression.

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