1 Department of Thoracic Surgery, Sanmen Chinese Medicine Hospital, Taizhou City, Zhejiang Province, China.
2 Department of Cardio-Thoracic Surgery, Sanmen People's Hospital, Taizhou City, Zhejiang Province, China.
Cancer Biother Radiopharm. 2019 Mar;34(2):119-127. doi: 10.1089/cbr.2018.2598. Epub 2019 Jan 14.
Calbindin 1 (CALB1), a constituent Ca-binding protein, has been reported to prevent apoptotic death in tumor cells. However, the microRNA-mediated regulatory mechanism of CALB1 expression in nonsmall cell lung cancer (NSCLC) has not been reported so far.
In this study, CALB1 was found to be overexpressed in NSCLC tissues through the immunohistochemistry assay. Higher CALB1 expression levels were significantly associated with the tumor-node-metastasis (TNM) stage. Moreover, higher expression of CALB1 predicts poor survival in NSCLC patients using the Kaplan-Meier plotter online analysis. In addition, miR-454-3p was predicted to target CALB1 using a software algorithm, validated by the luciferase assay, and analyzed by quantitative polymerase chain reaction and Western blot. The authors further found that miR-454-3p was downregulated in NSCLC tissues and cell lines. Downregulation of CALB1 or upregulation of miR-454-3p significantly suppressed NSCLC cell proliferation and induced cell apoptosis as shown by CCK-8 and flow cytometry analysis, respectively.
Our results suggest that CALB1 is a direct target of miR-454-3p and downregulation of CALB1 by miR-454-3p suppressed NSCLC cell functions, which may shed light on its potential application in NSCLC therapy.
钙结合蛋白 1(CALB1)是一种组成钙结合蛋白,已被报道可防止肿瘤细胞发生凋亡性死亡。然而,到目前为止,尚未有关于非小细胞肺癌(NSCLC)中 CALB1 表达的 microRNA 介导的调节机制的报道。
通过免疫组织化学检测,本研究发现 CALB1 在 NSCLC 组织中过表达。CALB1 表达水平较高与肿瘤-淋巴结-转移(TNM)分期显著相关。此外,Kaplan-Meier 绘图器在线分析表明,CALB1 高表达预示着 NSCLC 患者的生存不良。此外,通过软件算法预测 miR-454-3p 可靶向 CALB1,通过荧光素酶测定验证,并通过定量聚合酶链反应和 Western blot 进行分析。作者进一步发现,miR-454-3p 在 NSCLC 组织和细胞系中下调。CALB1 的下调或 miR-454-3p 的上调通过 CCK-8 和流式细胞术分析分别显著抑制了 NSCLC 细胞的增殖并诱导了细胞凋亡。
我们的研究结果表明,CALB1 是 miR-454-3p 的直接靶标,miR-454-3p 下调 CALB1 抑制了 NSCLC 细胞的功能,这可能为其在 NSCLC 治疗中的潜在应用提供了线索。