Feng Yan, Guo Xiangyu, Tang Huaping
Department of Respiratory Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Ann Transl Med. 2021 Feb;9(3):264. doi: 10.21037/atm-20-5984.
Solute carrier family 6 member 8 (SLC6A8) is known to be involved in the development of human tumors; however, the effect of SLC6A8 on the growth of non-small cell lung cancer (NSCLC) remains unclear. Here, we explored the role and potential action mechanism of SLC6A8 in NSCLC.
We used public databases [Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA)] to explore the expression of SLC6A8 in NSCLC. Additionally, we used immunohistochemistry to detect the expression of SLC6A8 in NSCLC clinicopathological tissues (cancer and adjacent tissues) and Western blotting to detect the expression of SLC6A8 in NSCLC clinicopathological tissues, NSCLC cell lines (A549, H1299, H520, and H1975), and a normal epithelial cell line (BEAS-2B). Using overexpression and knockdown of the gene, we analyzed the effects of SLC6A8 on the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC and also the possible molecular mechanism with Notch signaling pathway.
Bioinformatic analysis demonstrated that SLC6A8 is highly expressed in NSCLC and is related to poor prognosis. We found that the expression of the SLC6A8 protein in human lung cancer tissues was significantly higher than that in adjacent tissues. In addition, it was also significantly higher in lung cancer cell lines (A549, H1299, H520, and H1975) than that in normal lung epithelium-BEAS-2B. Moreover, SLC6A8 overexpression promotes the proliferation, migration and invasion in NSCLC, accompanied by the activation of notch signaling pathway and the up-regulation of MMP9 and E-cadherin proteins. Knocking down SLC6A8 can inhibit the above effects on cells.
SLC6A8 promotes the malignant progression of NSCLC and activates the Notch signaling pathway. Therefore, SLC6A8 is expected to become a molecular target for NSCLC treatment.
溶质载体家族6成员8（SLC6A8）已知参与人类肿瘤的发生发展；然而，SLC6A8对非小细胞肺癌（NSCLC）生长的影响仍不清楚。在此，我们探讨了SLC6A8在NSCLC中的作用及其潜在作用机制。
我们使用公共数据库[Oncomine、基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）]来探究SLC6A8在NSCLC中的表达情况。此外，我们采用免疫组织化学方法检测SLC6A8在NSCLC临床病理组织（癌组织和癌旁组织）中的表达，并用蛋白质印迹法检测SLC6A8在NSCLC临床病理组织、NSCLC细胞系（A549、H1299、H520和H1975）以及正常上皮细胞系（BEAS-2B）中的表达。通过基因过表达和敲低，我们分析了SLC6A8对NSCLC增殖、侵袭及上皮-间质转化（EMT）的影响，以及与Notch信号通路相关的可能分子机制。
生物信息学分析表明，SLC6A8在NSCLC中高表达且与预后不良相关。我们发现SLC6A8蛋白在人肺癌组织中的表达显著高于癌旁组织。此外，在肺癌细胞系（A549、H1299、H520和H1975）中其表达也明显高于正常肺上皮细胞系BEAS-2B。而且，SLC6A8过表达促进NSCLC的增殖、迁移和侵袭，同时伴随着Notch信号通路的激活以及MMP9和E-钙黏蛋白的上调。敲低SLC6A8可抑制上述对细胞的影响。
SLC6A8促进NSCLC的恶性进展并激活Notch信号通路。因此，SLC6A8有望成为NSCLC治疗的分子靶点。
