Department of Thoracic, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
Eur Rev Med Pharmacol Sci. 2019 Aug;23(16):6935-6943. doi: 10.26355/eurrev_201908_18733.
The aim of this study was to clarify the function of long noncoding ribonucleic acids (lncRNAs) small nucleolar RNA host gene 7 (SNHG7) in cisplatin-resistant non-small cell lung cancer (NSCLC), and to explore the potential mechanism.
SNHG7 expression in NSCLC and para-cancerous tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, the correlation between SNHG7 expression with clinical stage and cisplatin-resistance in NSCLC patients was analyzed. After transfection of si-SNHG7 or p-complementary deoxyribonucleic acid (pcDNA)-SNHG7, changes in cellular behaviors of A549/DDP cells were evaluated, including cell viability, apoptosis, migration, invasion and cell cycle. The regulatory effects of SNHG7 on the expressions of genes were determined by qRT-PCR as well. Furthermore, Western blot was conducted to determine the protein expressions of drug-resistance genes minimal residual disease1 (MRD1), P-glycoprotein (P-gp), BCRP and relative genes in phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.
Compared with adjacent normal tissues, SNHG7 was highly expressed in NSCLC tissues. Moreover, SNHG7 expression was significantly higher in advanced-stage NSCLC patients than those in early-stage. SNHG7 level remained significantly higher in DDP-resistant NSCLC tissues and cell lines as well. Knockdown of SNHG7 remarkably enhanced cisplatin-resistance in NSCLC cells, manifesting as decreased cell viability, migratory and invasive rates, DNA synthesis capacity, and promoted apoptosis. Meanwhile, SNHG7 knockdown down-regulated the mRNA levels of matrix metalloprotein2 (MMP2), MMP7 and MMP9 in vitro. After SNHG7 knockdown, the expressions of drug-resistant and relative genes in the PI3K/AKT pathway were notably down-regulated.
SNHG7 induces the development of cisplatin-resistance in NSCLC through upregulating MRD1 and BCRP via PI3K/AKT pathway.
本研究旨在阐明长链非编码核糖核酸（lncRNA）小核仁 RNA 宿主基因 7（SNHG7）在顺铂耐药非小细胞肺癌（NSCLC）中的作用，并探讨其潜在机制。
采用实时定量聚合酶链反应（qRT-PCR）检测 NSCLC 及癌旁组织中 SNHG7 的表达情况。同时，分析 NSCLC 患者 SNHG7 表达与临床分期及顺铂耐药的相关性。转染 si-SNHG7 或 pcDNA-SNHG7 后，评估 A549/DDP 细胞的细胞行为变化，包括细胞活力、凋亡、迁移、侵袭和细胞周期。通过 qRT-PCR 检测 SNHG7 对基因表达的调控作用。此外，通过 Western blot 检测耐药基因最小残留病 1（MRD1）、P-糖蛋白（P-gp）、BCRP 及磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）通路相关基因的蛋白表达。
与相邻正常组织相比，SNHG7 在 NSCLC 组织中高表达。此外，晚期 NSCLC 患者 SNHG7 表达明显高于早期患者。耐药 NSCLC 组织和细胞系中 SNHG7 水平也明显升高。SNHG7 敲低显著增强了 NSCLC 细胞的顺铂耐药性，表现为细胞活力、迁移和侵袭率、DNA 合成能力降低，促进凋亡。同时，SNHG7 敲低后，体外 MMP2、MMP7 和 MMP9 的 mRNA 水平下调。SNHG7 敲低后，PI3K/AKT 通路中耐药和相关基因的表达明显下调。
SNHG7 通过上调 PI3K/AKT 通路中的 MRD1 和 BCRP，诱导 NSCLC 顺铂耐药的发生。
