溶质载体家族6成员1通过调节PI3K/Akt信号通路磷酸化促进乳腺癌细胞的迁移和侵袭

吉磊; 徐洋; 唐楠

doi:10.16098/j.issn.0529-1356.2021.05.013

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解剖学报 ›› 2021, Vol. 52 ›› Issue (5) : 759-766. DOI: 10.16098/j.issn.0529-1356.2021.05.013

肿瘤生物学

溶质载体家族6成员1通过调节PI3K/Akt信号通路磷酸化促进乳腺癌细胞的迁移和侵袭

吉磊¹ 徐洋¹ 唐楠^2*

作者信息 +

Solute carrier family 6 member 1 promoting the proliferation and invasion of breast cancer cells through affecting the phosphorylation of PI3K/Akt signaling pathway

JI Lei¹ XU Yang¹ TANG Nan^2*

Author information +

文章历史 +

摘要

目的探讨溶质载体家族6成员1（SLC6A1）对乳腺癌细胞迁移和侵袭的影响及分子机制。方法下载并综合分析数据集GSE125989和GSE100534，筛选差异基因；通过STRING数据库和Cytoscape 3.6.1 软件构建差异基因的蛋白相互作用网络，并筛选hub基因；通过Ualcan和GEPIA数据库检测hub基因SLC6A1在乳腺癌中的表达及其对预后的影响；转染SLC6A1-siRNA干扰乳腺癌细胞MDA-MB-231中SLC6A1的表达；细胞划痕实验和Transwell实验检测乳腺癌细胞迁移和侵袭能力的变化；基因集富集分析和Western blotting检测SLC6A1在乳腺癌中发挥作用的机制；采用SC79激活Akt通路并检测细胞迁移和侵袭能力的变化。结果共筛选出92个乳腺癌原位癌与转移瘤的差异基因，并确定Ⅰ型胶原蛋白α1（COL1A1）、血管内皮生长因子A（VEGFA）、SLC6A1等20个hub基因；SLC6A1在乳腺癌组织中高表达（P＜0.001），且与患者预后相关（P=0.01）；SLC6A1表达被干扰后，乳腺癌细胞迁移和侵袭能力显著下降（P＜0.05）；SLC6A1表达降低可抑制PI3K/Akt信号通路的磷酸化（P＜0.05）；激活PI3K/Akt通路后 SLC6A1-siRNA对乳腺癌细胞迁移和侵袭的抑制作用消失（P＜0.05）。结论 SLC6A1通过调节PI3K/Akt信号通路促进乳腺癌的侵袭和转移。

Abstract

Objective To investigate the effects of solute carrier family 6 member 1 (SLC6A1) on migration and invasion of breast cancer cells and its molecular mechanism. Methods Data sets GSE125989 and GSE100534 were downloaded and comprehensively analyzed to screen the key genes. Protein interaction network of key genes was constructed by STRING database and Cytoscape 3.6.1 software, and hub genes were screened. Expression of hub gene SLC6A1 in breast cancer and its effect on prognosis were detected by Ualcan datebase and GEPIA datebase. SLC6A1-siRNA plasmid was transfected to interfere with SLC6A1 expression in breast cancer cells. Migration and invasion of breast cancer cells were detected by wound healing assay and Transwell assays. The mechanism of SLC6A1 in breast cancer was detected by gene set enrichment analysis and Western blotting. SC79 was used to activate the Akt pathway, and then detect changes in cell migration and invasion were detected. Results A total of 92 differentially expressed genes between metastatic breast cancer and carcinoma in situ were selected, and 20 hub genes including collagen Ⅰα1(COL1A1),vascular endothelial growth factor A(VEGFA) and SLC6A1 were selected. SLC6A1 were highly expressed in breast cancer tissues (P<0.001) and correlated with prognosis (P=0.01). After SLC6A1 interference, the migration and invasion of breast cancer cells decreased significantly (P<0.05). Inhibition of SLC6A1 expression can inhibit the phosphorylation of PI3K/Akt signaling pathway (P<0.05). Activation of the PI3K/Akt pathway eliminated the inhibitory effect of SLC6A1-siRNA on migration and invasion of breast cancer cells (P<0.05). Conclusion SLC6A1 promotes the migration and invasion of breast cancer cells through the PI3K/Akt signaling pathway.

导出引用

吉磊徐洋唐楠. 溶质载体家族6成员1通过调节PI3K/Akt信号通路磷酸化促进乳腺癌细胞的迁移和侵袭[J]. 解剖学报. 2021, 52(5): 759-766 https://doi.org/10.16098/j.issn.0529-1356.2021.05.013

JI Lei XU Yang TANG Nan. Solute carrier family 6 member 1 promoting the proliferation and invasion of breast cancer cells through affecting the phosphorylation of PI3K/Akt signaling pathway[J]. Acta Anatomica Sinica. 2021, 52(5): 759-766 https://doi.org/10.16098/j.issn.0529-1356.2021.05.013

中图分类号： R737.9

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