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Nucleotide exchange factor SIL1 promotes the progress of breast cancer cells via regulating the cell cycle and apoptosis.
Science Progress ( IF 2.6 ) Pub Date : 2019-12-02 , DOI: 10.1177/0036850419891046
Zhi-Feng Li 1 , Wei-Wei Xu 2 , Ji-Dan Li 1 , Feng-Ling Tao 1 , Jian-Xin Chen 1 , Jin-Hua Xu 3
Affiliation  

Breast cancer, as one of the most malignant tumors, poses a serious threat to the lives of females. Nucleotide exchange factor SIL1 is an important regulator of endoplasmic reticulum function that might have a specific role in tumor progression. In this study, we aimed to investigate the effect of SIL1 on the proliferation, apoptosis, and metastasis of human breast cancer. SIL1-specific small interfering RNA was transfected into two breast cancer cell lines, MCF7 and MDA-MB-231, to generate SIL1 knockdown cells. Clone formation and Cell Counting Kit-8 assays were performed to determine cell proliferation. Wound healing and transwell assays were used to detect the cell migration and invasion, respectively. Cell cycle and apoptosis were determined by flow cytometry. The messenger RNA and protein levels of target genes were analyzed using quantitative real-time PCR and western blot. According to the results of TCGA and GTEx database analysis, we determined that SIL1 was overexpressed in 1085 breast cancer samples compared with 291 normal samples. Knockdown of SIL1 inhibited the proliferation, migration, and invasion of MCF7 and MDA-MB-231 cells, accordingly. The cell cycle was blocked at the G1 phase following transfection of SIL1-specific small interfering RNA through the inhibition of Cyclin D1, CDK4, and CDK6. SIL1 knockdown induced apoptosis and also promoted the activity of Caspase9 and Bax. Furthermore, SIL1 was able to promote phosphorylation of ERK1/2. Based on these results, SIL1 might act as an oncogene and accelerate the progression of human breast cancer.

中文翻译:

核苷酸交换因子SIL1通过调节细胞周期和细胞凋亡促进乳腺癌细胞的进展。

乳腺癌作为最常见的恶性肿瘤之一,严重威胁着女性的生命。核苷酸交换因子 SIL1 是内质网功能的重要调节因子,可能在肿瘤进展中发挥特定作用。在本研究中,我们旨在探讨SIL1对人乳腺癌增殖、凋亡和转移的影响。将 SIL1 特异性小干扰 RNA 转染到两种乳腺癌细胞系 MCF7 和 MDA-MB-231 中,以产生 SIL1 敲低细胞。进行克隆形成和细胞计数 Kit-8 测定以确定细胞增殖。伤口愈合和transwell实验分别用于检测细胞迁移和侵袭。通过流式细胞术测定细胞周期和凋亡。使用定量实时PCR和蛋白质印迹分析靶基因的信使RNA和蛋白质水平。根据TCGA和GTEx数据库分析结果,我们确定与291个正常样本相比,1085个乳腺癌样本中SIL1过表达。相应地,SIL1 的敲低抑制了 MCF7 和 MDA-MB-231 细胞的增殖、迁移和侵袭。转染 SIL1 特异性小干扰 RNA 后,通过抑制 Cyclin D1、CDK4 和 CDK6,将细胞周期阻断在 G1 期。SIL1 敲低诱导细胞凋亡,并促进 Caspase9 和 Bax 的活性。此外,SIL1 能够促进 ERK1/2 的磷酸化。基于这些结果,SIL1 可能作为癌基因并加速人类乳腺癌的进展。
更新日期:2020-04-21
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