SNHG7 mediates cisplatin-resistance in non-small cell lung cancer by activating PI3K/AKT pathway.

Abstract

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.