Zhang Yuanyuan, Ma Haitao
Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Thoracic Surgery, Binhai County People's hospital, Yancheng, China.
J Thorac Dis. 2023 Mar 31;15(3):1289-1301. doi: 10.21037/jtd-23-153. Epub 2023 Mar 27.
Non-small cell lung cancer (NSCLC) is the most common malignancy in lung cancer, with a low survival rate and unfavorable prognosis. Dysregulated long non-coding RNAs (lncRNAs) play vital functions in tumor progression. This study intended to probe the expression pattern and function of in NSCLC.
Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the expression of , , , mRNA-decapping enzyme 1A (), and . Cell viability, migration, and invasion were separately examined via 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and transwell experiments. Luciferase reporter assay was conducted to evaluate the binding of with or . Protein expression of was assessed via Western blot. NSCLC animal models were constructed through injection of H1975 cells transfected with lentivirus (LV)-sh-HOXD-AS2 into nude mice, followed by hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) analysis.
In this study, was upregulated in NSCLC tissues and cells, and high predicted short overall survival (OS). Downregulation of could impair the proliferation, migration, and invasion abilities of H1975 and A549 cells. was shown to bind with and be lowly expressed in NSCLC. Suppression of could abolish the inhibitory effect of silencing on proliferation, migration, and invasion. was screened as the target of and its overexpression could rescue upregulation-repressed proliferation, migration, and invasion activities. Moreover, animal experiments affirmed that promoted tumor growth .
modulates the / axis to boost the progression of NSCLC, which founds the basis of as a new diagnostic biomarker and molecular target for NSCLC therapy.
非小细胞肺癌(NSCLC)是肺癌中最常见的恶性肿瘤,生存率低且预后不良。长链非编码RNA(lncRNA)失调在肿瘤进展中发挥重要作用。本研究旨在探究lncRNA HOXD-AS2在NSCLC中的表达模式及功能。
采用定量实时聚合酶链反应(qRT-PCR)分析HOXD-AS2、miR-195-5p、miR-497-5p、mRNA去帽酶1A(DCP1A)和HOXD10的表达。通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)和Transwell实验分别检测细胞活力、迁移和侵袭能力。进行荧光素酶报告基因检测以评估HOXD-AS2与miR-195-5p或miR-497-5p的结合。通过蛋白质免疫印迹法评估HOXD10的蛋白表达。将慢病毒(LV)-sh-HOXD-AS2转染的H1975细胞注射到裸鼠体内构建NSCLC动物模型,随后进行苏木精-伊红(HE)染色和免疫组织化学(IHC)分析。
在本研究中,HOXD-AS2在NSCLC组织和细胞中上调,高表达的HOXD-AS2预示着总生存期(OS)短。HOXD-AS2下调可损害H1975和A549细胞的增殖、迁移和侵袭能力。结果显示HOXD-AS2与miR-195-5p结合且在NSCLC中低表达。抑制miR-195-5p可消除HOXD-AS2沉默对增殖、迁移和侵袭的抑制作用。筛选出HOXD10作为miR-195-5p的靶标,其过表达可挽救HOXD-AS2上调所抑制的增殖、迁移和侵袭活性。此外,动物实验证实HOXD-AS2促进肿瘤生长。
HOXD-AS2通过调节miR-195-5p/HOXD10轴促进NSCLC进展,这为HOXD-AS2作为NSCLC新的诊断生物标志物和分子治疗靶点奠定了基础。