PDF(Pubmed)
Abstract：
Objective: This study investigates the relationship between the HOXA11-AS/let-7c-5p/IGF2BP1 regulatory axis and lung adenocarcinoma. Methods: The expression levels of HOXA11-AS, let-7c-5p, and IGF2BP1 were evaluated in LUAD tissue and cell lines. Subcellular fractionation detection assay was adopted to verify the HOXA11-AS distribution in LUAD cells. The interaction relationship between let-7c-5p and HOXA11-AS or IGF2BP1 was validated by dual-luciferase reporter detection. In RNA binding protein immunoprecipitation assay, the binding relationship between HOXA11-AS and let-7c-5p was identified. The cell viability of transfected cells was tested by the Cell Counting Kit-8 assay. The mouse xenograft model was used to identify the effect of HOXA11-AS on tumor growth in vivo. Results: Upregulation of lncRNA HOXA11-AS was found in LUAD, and suppression of HOXA11-AS could suppress the proliferative ability of LUAD cells. The let-7c-5p was expressed to be downregulated, which played an inhibitory role in LUAD cell proliferation. Let-7c-5p was negatively regulated by HOXA11-AS. HOXA11-AS promoted LUAD cell proliferation, while let-7c-5p had an inverse effect. Besides, IGF2BP1, regulated by let-7c-5p, had a positive relation with HOXA11-AS, while overexpression of IGF2BP1 could suppress the inhibition of silencing HOXA11-AS on LUAD cell proliferation. Experiments on mice confirmed that HOXA11-AS facilitated LUAD cell growth in vivo through regulating the let-7c-5p/IGF2BP1 axis. Conclusion: HOXA11-AS promoted LUAD cell proliferation by targeting let-7c-5p/IGF2BP1, which could be potential molecular targets for LUAD.
摘要：
目的:本研究探讨HOXA11-AS/let-7c-5p/IGF2BP1调节轴与肺腺癌的关系。方法:HOXA11-AS的表达水平,let-7c-5p,在LUAD组织和细胞系中评估IGF2BP1。采用亚细胞分级分离检测法验证HOXA11-AS在LUAD细胞中的分布。通过双荧光素酶报告基因检测验证了let-7c-5p与HOXA11-AS或IGF2BP1之间的相互作用关系。在RNA结合蛋白免疫沉淀试验中，确定了HOXA11-AS和let-7c-5p之间的结合关系。通过细胞计数试剂盒-8测定法测试转染细胞的细胞活力。使用小鼠异种移植模型来鉴定HOXA11-AS对体内肿瘤生长的影响。结果：在LUAD中发现lncRNAHOXA11-AS上调，抑制HOXA11-AS可以抑制LUAD细胞的增殖能力。let-7c-5p表达下调，对LUAD细胞增殖有抑制作用。let-7c-5p受HOXA11-AS负调控。HOXA11-AS促进LUAD细胞增殖，而let-7c-5p有相反的效果。此外,IGF2BP1，受let-7c-5p调节，与HOXA11-AS呈正相关，而IGF2BP1的过表达可以抑制沉默HOXA11-AS对LUAD细胞增殖的抑制作用。小鼠实验证实HOXA11-AS通过调节let-7c-5p/IGF2BP1轴促进LUAD细胞在体内生长。结论:HOXA11-AS通过靶向let-7c-5p/IGF2BP1促进LUAD细胞增殖,可能成为LUAD潜在的分子靶点。
