Yifei Ma, Guoning Li, Haoyang Yu, Baoke Wang, Zhihan Diao, Yuan Du, Hongbo Wang, Huiping Liu
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引用次数: 0
Abstract
The transient receptor potential channel 6 (TRPC6), a Ca2+-permeable, non-selective cation channel, is a potential drug target widely expressed in most human tissues. However, the role of TRPC6 in breast cancer remains largely unknown. We comprehensively investigated the relationships between TRPC6 and breast cancer using online databases, including TIMER, cBioPortal, UALCAN, the Kaplan-Meier plotter, the Human Protein Atlas, STRING, and the LinkedOmics, to evaluate the prognostic value of TRPC6. We also tentatively explored the effects of TRPC6 modulation on proliferation and metastasis potential in several breast cancer cell lines by MTT assay, colony formation assay, flow cytometry, and scratch wound healing assay. The TCGA data showed lower TRPC6 gene expression in breast tumours versus normal breast tissues. The Human Protein Atlas revealed that the TRPC6 protein was generally expressed at low levels in both normal and breast carcinoma tissue. The Kaplan-Meier plotter showed that the low TRPC6 level is correlated with worse relapse-free survival probability in breast cancer. Moreover, the TRPC6 gene was linked to immune infiltration in breast cancer, and this relationship affected the prognosis of breast cancer. In contrast to published researches, we found that TRPC6 expression was negatively correlated with breast cancer cell proliferation and metastasis abilities, suggesting TRPC6 as a promising prognostic biomarker for breast cancer, where low expression of TRPC6 was related to worse prognoses. This research raises the necessity of rethinking the mechanism perspective and targetability of TRPC6 in breast cancer, which warrants further investigation.
瞬时受体电位通道6 (TRPC6)是一种Ca2+可渗透的非选择性阳离子通道,是在大多数人体组织中广泛表达的潜在药物靶点。然而,TRPC6在乳腺癌中的作用在很大程度上仍然未知。我们利用TIMER、cbiopportal、UALCAN、Kaplan-Meier绘图仪、Human Protein Atlas、STRING和LinkedOmics等在线数据库,全面研究了TRPC6与乳腺癌的关系,以评估TRPC6的预后价值。我们还通过MTT实验、集落形成实验、流式细胞术和抓伤愈合实验,初步探讨了TRPC6调控对几种乳腺癌细胞系增殖和转移潜能的影响。TCGA数据显示,与正常乳腺组织相比,乳腺肿瘤中的TRPC6基因表达较低。人类蛋白图谱显示,TRPC6蛋白在正常和乳腺癌组织中普遍表达水平较低。Kaplan-Meier绘图图显示,低TRPC6水平与乳腺癌患者较差的无复发生存率相关。此外,TRPC6基因与乳腺癌的免疫浸润有关,并影响乳腺癌的预后。与已发表的研究相比,我们发现TRPC6的表达与乳腺癌细胞的增殖和转移能力呈负相关,提示TRPC6是一种很有希望的乳腺癌预后生物标志物,其中TRPC6的低表达与预后较差有关。本研究提出了重新思考TRPC6在乳腺癌中的机制视角和靶向性的必要性,值得进一步研究。