Ni Jun, Peng Yun, Yang Fu-Lan, Xi Xun, Huang Xing-Wei, He Chun
Department of Breast and Thyroid Surgery, People's Hospital of Ganzhou City, Ganzhou, Jiangxi, People's Republic of China.
Onco Targets Ther. 2018 Jun 4;11:3303-3312. doi: 10.2147/OTT.S161311. eCollection 2018.
The aim of this study was to evaluate the expression of C-type lectin domain family 3 member A (CLEC3A) and its clinical significance in breast invasive ductal cancer (IDC) as well as its effect on breast cancer (BC) cell proliferation and metastasis. In this study, the level of CLEC3A expression in The Cancer Genome Atlas (TCGA) datasets was analyzed.
Clinical collected samples and BC cells were measured using quantitative reverse transcription polymerase chain reaction. Its correlations with patients' clinicopathological characteristics were analyzed by Pearson's chi-squared test. Overall survival (OS) analysis was performed by the Kaplan-Meier method and Cox's proportional-hazards model. BC cell proliferation, migration, and invasion by CLEC3A knockdown were assessed using Cell Counting Kit-8 and colony formation assay, wound healing model and transwell assay, respectively, in BT474 cell line. Activities of survival factors and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling were measured by testing key molecules using Western blot assay.
CLEC3A expression was markedly higher in breast IDC tissues than normal breast tissues or adjacent normal tissue. Patients with high CLEC3A expression related to higher lymph node and poorer OS of breast IDC. CLEC3A knockdown by siRNA could inhibit the BC cells BT474 proliferation, migration, and invasion, together with a decrease in expression of key proteins in survival factors and PI3K/AKT signaling pathway.
Elevated CLEC3A expression may correlate with breast IDC metastatic potential and indicated a poor prognosis in breast IDC. CLEC3A knockdown inhibited BC cell growth and metastasis might be through suppressing PI3K/AKT signaling activity. These findings unravel that CLEC3A is a promising therapeutic target for BC in the future.
本研究旨在评估C型凝集素结构域家族3成员A（CLEC3A）在乳腺浸润性导管癌（IDC）中的表达及其临床意义，以及其对乳腺癌（BC）细胞增殖和转移的影响。在本研究中，分析了癌症基因组图谱（TCGA）数据集中CLEC3A的表达水平。
使用定量逆转录聚合酶链反应检测临床收集的样本和BC细胞。通过Pearson卡方检验分析其与患者临床病理特征的相关性。采用Kaplan-Meier法和Cox比例风险模型进行总生存（OS）分析。在BT474细胞系中，分别使用细胞计数试剂盒-8和集落形成试验、伤口愈合模型和Transwell试验评估CLEC3A敲低对BC细胞增殖、迁移和侵袭的影响。通过蛋白质免疫印迹法检测关键分子，测定生存因子和磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（AKT）信号通路的活性。
CLEC3A在乳腺IDC组织中的表达明显高于正常乳腺组织或癌旁正常组织。CLEC3A高表达的患者与乳腺IDC的淋巴结转移率较高和OS较差相关。siRNA敲低CLEC3A可抑制BC细胞BT474的增殖、迁移和侵袭，同时降低生存因子和PI3K/AKT信号通路中关键蛋白的表达。
CLEC3A表达升高可能与乳腺IDC的转移潜能相关，并提示乳腺IDC预后不良。敲低CLEC3A抑制BC细胞生长和转移可能是通过抑制PI3K/AKT信号活性实现的。这些发现表明，CLEC3A是未来BC有前景的治疗靶点。
