长链非编码 RNA BC200 通过 PI3K/AKT 通路调节非小细胞肺癌细胞的增殖和顺铂耐药性。
LncRNA BC200 regulates the cell proliferation and cisplatin resistance in non-small cell lung cancer via PI3K/AKT pathway.
机构信息
Cancer Treatment Center, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1093-1101. doi: 10.26355/eurrev_201902_16999.
OBJECTIVE
Long non-coding RNA (lncRNA) exerts tissue specificity and regulates the occurrence and progression of tumors. Previous bioinformatics showed that lncRNA BC200 is served as an oncogene. However, the specific role of BC200 in lung cancer (LC) is rarely reported. The aim of this study is to elucidate the regulatory effects of BC200 on tumor development and cisplatin resistance in non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS
The expression level of BC200 in 76 pairs of NSCLC tissues and adjacent normal tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation analyses were conducted to investigate the relation between BC200 expression and prognosis of NSCLC patients. Subsequently, BC200 expression in LC cell lines was detected. After construction of si-BC200 and si-NC, the cellular functions of LC cells were detected through colony formation, flow cytometry and transwell assay, respectively. Western blot was performed to detect the protein expressions of key genes in the PI3K/AKT pathway in LC cells. Finally, cell counting kit-8 (CCK-8) assay was carried out to explore the effect of BC200 on cisplatin resistance of LC cells via calculating IC50.
RESULTS
Higher expression of BC200 was found in NSCLC tissues than that of adjacent normal tissues. BC200 expression was positively correlated with tumor stage, lymph node metastasis and distant metastasis of NSCLC patients, whereas not correlated to age and sex. Knockdown of BC200 inhibited proliferation, invasion and migration of LC cells. Western blot results showed that protein expressions of PI3K, AKT and STAT3 were downregulated after BC200 knockdown in LC cells. Additionally, the IC50 in H1299/DDP cells transfected with si-BC200 was lower than in those transfected with si-NC. The apoptotic rate in H1299 cells transfected with si-BC200 was remarkably lower than those transfected with si-NC.
CONCLUSIONS
BC200 is highly expressed in NSCLC, which is positively correlated with tumor stage and metastasis of NSCLC patients. BC200 promotes the malignant progression of NSCLC via regulating cisplatin-induced apoptosis of H1299/DDP cells.
目的
长链非编码 RNA（lncRNA）具有组织特异性，调节肿瘤的发生和发展。先前的生物信息学研究表明，lncRNA BC200 是一种癌基因。然而，BC200 在非小细胞肺癌（LC）中的具体作用鲜有报道。本研究旨在阐明 BC200 对非小细胞肺癌肿瘤发生和顺铂耐药性的调控作用。
患者和方法
通过实时定量聚合酶链反应（qRT-PCR）检测 76 对 NSCLC 组织和相邻正常组织中 BC200 的表达水平。进行相关性分析以探讨 BC200 表达与 NSCLC 患者预后的关系。随后，检测 LC 细胞系中 BC200 的表达。构建 si-BC200 和 si-NC 后，分别通过集落形成、流式细胞术和 Transwell 测定法检测 LC 细胞的细胞功能。Western blot 检测 LC 细胞中 PI3K/AKT 通路关键基因的蛋白表达。最后，通过计算 IC50，细胞计数试剂盒-8（CCK-8）测定法研究 BC200 对 LC 细胞顺铂耐药性的影响。
结果
与相邻正常组织相比，非小细胞肺癌组织中 BC200 的表达更高。BC200 的表达与 NSCLC 患者的肿瘤分期、淋巴结转移和远处转移呈正相关，而与年龄和性别无关。BC200 敲低抑制 LC 细胞的增殖、侵袭和迁移。Western blot 结果显示，LC 细胞中 BC200 敲低后 PI3K、AKT 和 STAT3 的蛋白表达下调。此外，转染 si-BC200 的 H1299/DDP 细胞的 IC50 低于转染 si-NC 的细胞。转染 si-BC200 的 H1299 细胞的凋亡率明显低于转染 si-NC 的细胞。
结论
BC200 在 NSCLC 中高表达，与 NSCLC 的肿瘤分期和转移呈正相关。BC200 通过调节 H1299/DDP 细胞顺铂诱导的凋亡促进 NSCLC 的恶性进展。
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