长链非编码 RNA（lncRNA）癌症易感性候选物 2c（CASC2c）通过 ERK1/2 和 β-连环蛋白信号通路对非小细胞肺癌（NSCLC）细胞增殖、转移和耐药性的影响。
Effects of long non-coding RNA (lncRNA) cancer susceptibility candidate 2c (CASC2c) on proliferation, metastasis and drug resistance of non-small cell lung cancer (NSCLC) cells through ERK1/2 and β-catenin signaling pathways.
机构信息
Department of Pharmacy, Jiangxi Provincial People's Hospital, Aiguo Road 152, Donghu, Nanchang, Jiangxi, People's Republic of China.
出版信息
Pathol Res Pract. 2019 Sep;215(9):152522. doi: 10.1016/j.prp.2019.152522. Epub 2019 Jun 27.
OBJECTIVES
This study was aimed to investigate the effects of long non-coding RNA (lncRNA) cancer susceptibility candidate 2c (CASC2c) on the proliferation, metastasis and drug resistance of non-small cell lung cancer (NSCLC) cells.
METHODS
The expression of CASC2c in NSCLC tissues and cell lines was detected by real-time fluorescence quantitative PCR (RT-qPCR). MTT and Transwell assay were used to determine the proliferation and migration of NSCLC cells in the experimental group and the control group respectively. The drug sensitivity test was used to confirm whether increasing the CASC2c expression level could reverse the resistance of NSCLC cells to the chemotherapy drug cisplatin. The effects of CASC2c on the expression levels of p-ERK1/2 and β-catenin were detected by western blot.
RESULTS
The results of RT-qPCR showed that CASC2c was under-expressed in NSCLC tissues and cells compared with normal adjacent lung tissues cells (p < 0.05). In addition, the CASC2c expression was remarkably correlated with TNM staging, tumor cell differentiation, lymph node metastasis, smoking and other pathological indicators of patients with NSCLC (p < 0.05). MTT and Transwell assay showed that the high-expression of CASC2c significantly reduced the proliferation and migration of NSCLC cells compared to that of the control group (p < 0.05). Western blot assay showed that the high-expressed CASC2c can decrease the expression of phosphorylated-ERK1/2 (p-ERK1/2) and β-catenin.
CONCLUSIONS
CASC2c was low expressed in NSCLC tissues and cells. What's more, it inhibited the proliferation and migration of NSCLC cells by inhibiting the expression of p-ERK1/2 and β-catenin and reversed NSCLC cells' resistance to the chemotherapy drug cisplatin. Therefore, CASC2c may serve as a new biomarker and therapeutic target in the diagnosis and treatment of NSCLC.
目的
本研究旨在探讨长链非编码 RNA（lncRNA）癌症易感性候选物 2c（CASC2c）对非小细胞肺癌（NSCLC）细胞增殖、转移和耐药性的影响。
方法
采用实时荧光定量 PCR（RT-qPCR）检测 NSCLC 组织和细胞系中 CASC2c 的表达。MTT 和 Transwell 实验分别用于检测实验组和对照组 NSCLC 细胞的增殖和迁移。药敏试验用于确认增加 CASC2c 表达水平是否能逆转 NSCLC 细胞对化疗药物顺铂的耐药性。Western blot 检测 CASC2c 对 p-ERK1/2 和 β-catenin 表达水平的影响。
结果
RT-qPCR 结果显示，与正常相邻肺组织细胞相比，CASC2c 在 NSCLC 组织和细胞中表达下调（p<0.05）。此外，CASC2c 的表达与 NSCLC 患者的 TNM 分期、肿瘤细胞分化、淋巴结转移、吸烟等病理指标显著相关（p<0.05）。MTT 和 Transwell 实验表明，与对照组相比，CASC2c 的高表达显著降低了 NSCLC 细胞的增殖和迁移（p<0.05）。Western blot 实验表明，高表达的 CASC2c 可降低磷酸化-ERK1/2（p-ERK1/2）和 β-catenin 的表达。
结论
CASC2c 在 NSCLC 组织和细胞中低表达。此外，它通过抑制 p-ERK1/2 和 β-catenin 的表达抑制 NSCLC 细胞的增殖和迁移，并逆转 NSCLC 细胞对化疗药物顺铂的耐药性。因此，CASC2c 可能成为 NSCLC 诊断和治疗的新的生物标志物和治疗靶点。
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