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转移抑制因子 1 通过抑制三阴性乳腺癌中的上皮间质转化发挥肿瘤抑制作用。

Metastasis suppressor 1 acts as a tumor suppressor by inhibiting epithelial-to-mesenchymal transition in triple-negative breast cancer.

机构信息

Department of Breast Surgery, Shanghai Changning Maternity & Infant Health Hospital, Shanghai, China.

Department of Pathology, Shanghai Changning Maternity & Infant Health Hospital, Shanghai, China.

出版信息

Int J Biol Markers. 2020 Mar;35(1):74-81. doi: 10.1177/1724600820905114. Epub 2020 Feb 13.

Abstract

OBJECTIVE

This study aimed to analyze the function of metastasis suppressor 1 () in triple negative breast cancer (TNBC).

METHODS

expression in 30 TNBC and paracancerous tissues was measured by quantitative reverse transcriptase polymerase chain reaction. The prognostic value of was assessed by Kaplan-Meier analysis followed by the log-rank test. MCF7 cells were transfected with si-, while MDA-MB-231 cells were transfected with pcDNA3.1-. Cell proliferation assay and transwell assay were performed to investigate the effects of on the biological behavior of breast cancer cells. Immunofluorescence and western blot were used to detect the influence of on epithelial-mesenchymal transition (EMT) markers.

RESULTS

expression was significantly lower in TNBC tissues compared with that in paracancerous tissues (0.012 vs. 0.370; = 0.006). A lower expression level was also found in tumor tissues of patients with lymph node metastasis ( = 0.002) or tumor node metastasis stage ( = 0.010). Patients with low expression of (⩽ 0.009) had shorter disease-free survival (47.4 vs. 56.0 months; = 0.012). The knockdown of in MCF7 cells inhibited cell proliferation, enhanced cell migration and invasion capacities, decreased the E-cadherin level, and increased the vimentin level, whereas overexpression of in MDA-MB-231 cells had the opposite effects ( < 0.05).

CONCLUSIONS

Our findings demonstrated that regulates proliferation, invasion, migration, and EMT in TNBC, and that decreased is associated with shorter disease-free survival.

摘要

目的

本研究旨在分析转移抑制因子 1()在三阴性乳腺癌(TNBC)中的作用。

方法

通过定量逆转录聚合酶链反应检测 30 例 TNBC 及癌旁组织中的表达。采用 Kaplan-Meier 分析结合对数秩检验评估的预后价值。MCF7 细胞转染 si-,MDA-MB-231 细胞转染 pcDNA3.1-。通过细胞增殖实验和 Transwell 实验研究对乳腺癌细胞生物学行为的影响。免疫荧光和 Western blot 检测对上皮-间充质转化(EMT)标志物的影响。

结果

与癌旁组织相比,TNBC 组织中表达明显降低(0.012 比 0.370;=0.006)。淋巴结转移(=0.002)或肿瘤淋巴结转移分期(=0.010)患者肿瘤组织中也发现表达水平较低。表达水平低(⩽0.009)的患者无病生存时间较短(47.4 比 56.0 个月;=0.012)。MCF7 细胞中沉默可抑制细胞增殖,增强细胞迁移和侵袭能力,降低 E-钙黏蛋白水平,增加波形蛋白水平,而 MDA-MB-231 细胞中过表达则产生相反的效果(<0.05)。

结论

我们的研究结果表明,在 TNBC 中,通过调节增殖、侵袭、迁移和 EMT,下调与无病生存时间缩短有关。

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