[摘 要] 目的：基于生物信息学分析和体内、体外实验研究长链非编码RNA00511（LINC00511）敲减对非小细胞肺癌细胞增 殖、凋亡、侵袭等恶性生物学行为的影响，并初步探究其作用机制。方法：通过基因表达谱交互分析（GEPIA）数据库分析 LINC00511在非小细胞肺癌的表达水平，及其与患者肿瘤分期、生存期等临床特征、肿瘤细胞恶性生物学行为有关基因的相关 性；利用shRNA慢病毒载体构建LINC00511敲减的H1299肺癌细胞株，克隆形成实验、划痕愈合实验和流式细胞术分别检测对 H1299细胞增殖、迁移、细胞周期和凋亡能力的影响，qRT-PCR检测相关调控基因表达，WB法检测肿瘤相关蛋白的表达；构建裸 鼠皮下移植瘤模型，取瘤组织进行免疫组织化学实验检测Ki67表达情况。结果：GEPIA数据库分析表明LINC00511在非小细胞 肺癌组织中表达水平升高，且与该病的临床分期情况相关（P < 0.05），LINC00511与肺癌中CASP3、CCNB1、CDK4等多种基因表 达均有相关性（P < 0.01）；LINC00511敲减可抑制细胞的克隆形成和迁移能力、促进肺癌细胞凋亡并影响细胞周期进展（P < 0.05， P < 0.01）；LINC00511敲减可下调肺癌细胞CCNB、CDK4、TGF-β1基因的表达（P < 0.01），对CCND1、VEGFA基因表达无明显影 响，LINC00511敲减可抑制细胞内MMP9、CTNNB1表达，上调CASP3的表达（P < 0.05，P < 0.01）；裸鼠体内实验证实，LINC00511 敲减可抑制移植瘤体组织内Ki67的表达（P < 0.01）。结论：LINC00511在非小细胞肺癌组织中呈高表达，与肺癌临床分期和多 种基因表达具有相关性，LINC00511敲减可能通过影响相关基因、蛋白的表达，抑制肺癌H1299细胞的恶性生物学行为。

[Abstract] Objective: To investigate the effects of long non-coding RNA LINC00511 (LINC00511) knockdown on the proliferation, apoptosis, invasion, and other malignant biological behaviors of non-small cell lung cancer (NSCLC) cells through bioinformatics analysis, in vivo and in vitro experiments, and to preliminarily explore its underlying mechanisms. Methods: The gene Expression profiling Interaction analysis (GEPIA) database was used to analyze the expression level of LINC00511 in NSCLC, and its correlation with clinical characteristics such as tumor stage and survival period of patients, as well as genes related to the malignant biological behaviors of tumor cells. The H1299 lung cancer cell line with LINC00511 knockdown was constructed using shRNA lentiviral vectors. The effects on the proliferation, migration, cell cycle and apoptosis of H1299 cells were detected by clone formation assay, scratch healing assay and flow cytometry, respectively. The expressions of related regulatory genes were detected by qRT-PCR, and the expressions of tumor-related proteins were detected by WB assay. A subcutaneous transplanted tumor model was constructed in nude mice, and the tumor tissues were taken for immunohistochemical experiments to detect the expression of Ki67. Results: GEPIA database analysis showed that the expression level of LINC00511 was elevated in NSCLC tissues and correlated with the clinical stage of the disease (P < 0.05). LINC00511 was correlated with the expressions of CASP, CCNB1, CDK4 and other genes in lung cancer (P < 0.01). Knockdown of LINC00511 could inhibit cell colony formation and migration abilities, promote the apoptosis of lung cancer cells, and affect cell cycle progression (P < 0.05, P < 0.01). LINC00511 knockdown could down-regulate the expressions of CCNB, CDK4 and TGF-β1 genes in lung cancer cells (P < 0.01), but had no significant effect on the expressions of CCND1 and VEGFA genes. LINC00511 knockdown could inhibit the expressions of MMP9 and CTNNB1, and up-regulated the expression of CASP3 (P < 0.05, P < 0.01). In vivo experiments in nude mice confirmed that LINC00511 knockdown could inhibit Ki67 expression in transplanted tumor tissues (P < 0.01). Conclusion: LINC00511 is highly expressed in non-small cell lung cancer tissues and is correlated with the clinical stage of lung cancer and the expressions of multiple genes. LINC00511 Knockdown of LINC00511 can inhibit the malignant biological behaviors of lung cancer H1299 cells by affecting the expressions of related genes and proteins.

[基金项目] 齐齐哈尔市科技计划联合引导项目（No. LSFGG-2023046）；黑龙江省省属高等学校基本科研业务费科研项目 （No.2019-KYYWF-1219）；齐齐哈尔医学科学院重点培育项目（No. 2022-ZDPY-011）