esiRNA 介导的 HIF1A 沉默可调控 MDA-MB-231 细胞的迁移、侵袭、凋亡和增殖

Q4 Biochemistry, Genetics and Molecular Biology
S. S. Sharaf, A. Lekshmi, K. Sujathan
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引用次数: 0

摘要

摘要 该研究表明,使用esiRNA(内切酶制备的小干扰RNA)沉默HIF1A基因可抑制乳腺癌细胞增殖、提高细胞凋亡率、抑制细胞侵袭和迁移。这些结果表明,HIF1A 基因可能参与了三阴性乳腺癌表型的发生和发展。缺氧是大多数实体瘤的重要特征。在乳腺癌中,缺氧在 TNBC(三阴性乳腺癌)中比在其他乳腺癌亚型中更为明显。TNBC 的瘤内分析表明,缺氧程度高的肿瘤区域表明 HIF1A 的表达较高。在此,我们研究了沉默 HIF1A 对三阴性乳腺癌生物学功能的影响。我们采用逆转录聚合酶链反应和免疫印迹法检测不同乳腺癌细胞和患者组织中 HIF1A 的表达。然后,进行 BrdU 检测以研究细胞增殖。此外,通过Annexin V/碘化丙啶染色和Caspase检测法检测了HIF1A基因敲除后的细胞凋亡情况,并通过跨孔检测法检测了细胞的迁移和侵袭情况。IHC分析表明,HIF1A在TNBC组织中强过表达。沉默表明,HIF1A 能显著促进细胞增殖和迁移,导致转移,并能下调细胞凋亡。抑制HIF1A表达的MDA-MB-231细胞侵袭性降低,耐缺氧能力减弱,迁移受阻,凋亡增加,导致转移的能力减弱。HIF1A 可能是驱动三阴性乳腺癌转移进展和凋亡的主导因子,可以成为该疾病的有效治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

esiRNA Mediated Silencing of HIF1A Regulates Migration, Invasion, Apoptosis, and Proliferation of MDA-MB-231 Cells

esiRNA Mediated Silencing of HIF1A Regulates Migration, Invasion, Apoptosis, and Proliferation of MDA-MB-231 Cells

Abstract

This study demonstrated that silencing of HIF1A using esiRNA (endoribonuclease prepared small interfering RNA) could inhibit breast cancer cells proliferation, increase the apoptosis rate, and inhibit cell invasion and migration. These results suggested that HIF1A gene may involve in the occurrence and development of triple negative breast cancer phenotype. Hypoxia is an important hallmark of most solid tumors. In breast cancer, hypoxia is more evident in TNBC (triple negative breast cancer) than in other breast cancer subtypes. Intratumoral analysis in TNBC showed that tumor areas with high levels of hypoxia, indicated higher expression of HIF1A. Here we investigated the effect of silencing HIF1A on the biological function of triple negative breast cancer. Reverse transcription-polymerase chain reaction and western blot were used to detect HIF1A expression in different breast cancer cells and patient tissues. esiRNA was used to silence HIF1A in MDA-MB-231 cells. Then, BrdU assay was performed to study cell proliferation. Additionally, cell apoptosis after HIF1A knockdown was measured by Annexin V/propidium iodide staining followed by Caspase assay, and cell migration and invasion was detected by trans-well assay. IHC analysis suggested a strong overexpression of HIF1A in TNBC tissues. Silencing suggested that HIF1A significantly promotes cell proliferation and migration, resulting in metastasis and downregulates apoptosis. MDA-MB-231 cells in which HIF1A expression was inhibited were less invasive, with reduced resistance to hypoxia, impaired migration, increased apoptosis and reduced capacity to cause metastasis. HIF1A may be a dominant factor driving the metastatic progression and apoptosis of triple negative breast cancer and can be a potent therapeutic target for the disease.

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来源期刊
Cell and Tissue Biology
Cell and Tissue Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
0.80
自引率
0.00%
发文量
51
期刊介绍: The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.
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