Department of Respiration Medicine, Fujian Medical University Union Hospital, No.29 Xin Quan Road, Fuzhou, 350000, Fujian, China.
Fujian Provincial Key Laboratory of Medical Testing, Fujian Academy of Medical Sciences, Fuzhou, 350000, Fujian, China.
Diagn Pathol. 2023 Mar 2;18(1):33. doi: 10.1186/s13000-023-01291-2.
Lung adenocarcinoma (LUAD) is a prevalent malignancy. SNHG15 has been demonstrated to be oncogenic in many kinds of cancers, however the mechanism of SNHG15 in LUAD cisplatin (DDP) resistance remains unclear. In this study, we demonstrated the effect of SNHG15 on DDP resistance in LUAD and its related mechanism.
Bioinformatics analysis was adopted to assess SNHG15 expression in LUAD tissues and predict the downstream genes of SNHG15. The binding relationship between SNHG15 and downstream regulatory genes was proved through RNA immunoprecipitation, chromatin immunoprecipitation and dual-luciferase reporter assays. Cell counting kit-8 assay was adopted to evaluate LUAD cell viability, and gene expression was determined by Western blot and quantitative real-time polymerase chain reaction. We then performed comet assay to assess DNA damage. Cell apoptosis was detected by Tunnel assay. Xenograft animal models were created to test the function of SNHG15 in vivo.
SNHG15 was up-regulated in LUAD cells. Moreover, SNHG15 was also highly expressed in drug-resistant LUAD cells. Down-regulated SNHG15 strengthened the sensitivity of LUAD cells to DDP and induced DNA damage. SNHG15 could elevate ECE2 expression through binding with E2F1, and it could induce DDP resistance by modulating the E2F1/ECE2 axis. In vivo experiments verified that the SNHG15 could enhance DDP resistance in LUAD tissue.
The results suggested that SNHG15 could up-regulate ECE2 expression by recruiting E2F1, thereby enhancing the DDP resistance of LUAD.
肺腺癌（LUAD）是一种常见的恶性肿瘤。SNHG15 在许多类型的癌症中被证明具有致癌性，然而其在 LUAD 顺铂（DDP）耐药中的机制尚不清楚。在本研究中，我们证明了 SNHG15 对 LUAD 中 DDP 耐药的影响及其相关机制。
采用生物信息学分析评估 LUAD 组织中 SNHG15 的表达，并预测 SNHG15 的下游基因。通过 RNA 免疫沉淀、染色质免疫沉淀和双荧光素酶报告基因检测证实 SNHG15 与下游调控基因的结合关系。通过细胞计数试剂盒-8 检测 LUAD 细胞活力，并通过 Western blot 和定量实时聚合酶链反应测定基因表达。然后进行彗星试验评估 DNA 损伤。通过Tunnel 试验检测细胞凋亡。建立异种移植动物模型来体内检测 SNHG15 的功能。
SNHG15 在 LUAD 细胞中上调。此外，耐药 LUAD 细胞中 SNHG15 的表达也较高。下调 SNHG15 可增强 LUAD 细胞对 DDP 的敏感性并诱导 DNA 损伤。SNHG15 可通过与 E2F1 结合来上调 ECE2 的表达，并通过调节 E2F1/ECE2 轴诱导 DDP 耐药。体内实验验证了 SNHG15 可增强 LUAD 组织中 DDP 的耐药性。
研究结果表明，SNHG15 可通过募集 E2F1 上调 ECE2 的表达，从而增强 LUAD 的 DDP 耐药性。
