Jiang Xiulin, Tang Lin, Yuan Yixiao, Wang Juan, Zhang Dahang, Qian Kebao, Cho William C, Duan Lincan
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/ Kunming Institute of Zoology, Kunming, China.
The Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming, China.
Front Oncol. 2022 Mar 3;12:846536. doi: 10.3389/fonc.2022.846536. eCollection 2022.
Hyaluronan-mediated motility receptor () plays a pivotal role in cell proliferation in various cancers, including lung cancer. However, its function and biological mechanism in lung adenocarcinoma (LUAD) remain unclear.
Data on expression from several public databases were extensively analyzed, including the prognosis of in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using DAVID and gene set enrichment analysis (GSEA) software. The correlation between expression and immune cell infiltration was analyzed in the Tumor Immune Estimation Resource (TIMER) database, and the gene and protein networks were examined using the GeneMANIA and STRING databases. Experimentally, the expression of in LUAD and lung cancer cell lines was determined using immunohistochemistry and quantitative RT-PCR assays. Besides, the function of on cancer cell proliferation and migration was examined using cell growth curve and colony formation, Transwell, and wound healing assays.
In this study, we found that was elevated in LUAD and that its high expression was associated with poor clinicopathological features and adverse outcomes in LUAD patients. Furthermore, our results demonstrated that the expression of was positively correlated with immune cell infiltration and immune modulation. Interestingly, diverse immune cell infiltration affects the prognosis of LUAD. In the functional assay, depletion of significantly repressed the cancer cell growth and migration of LUAD. Mechanically, we found that that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of in LUAD. Depletion of TMPO-AS1 and overexpression of let-7b-5p could result in the decreased expression of in LUAD cells. Furthermore, we found that TMPO-AS1 was positively correlated with , yet negatively correlated with let-7b-5p expression in LUAD.
Our findings elucidated that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of , which may be considered as a biomarker to predict prognosis in LUAD.
透明质酸介导的运动受体（）在包括肺癌在内的多种癌症的细胞增殖中起关键作用。然而，其在肺腺癌（LUAD）中的功能和生物学机制仍不清楚。
广泛分析了来自几个公共数据库的表达数据，包括基因表达谱交互分析（GEPIA）数据库中的预后情况。使用DAVID和基因集富集分析（GSEA）软件分析基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路。在肿瘤免疫评估资源（TIMER）数据库中分析表达与免疫细胞浸润之间的相关性，并使用GeneMANIA和STRING数据库检查基因和蛋白质网络。实验上，使用免疫组织化学和定量RT-PCR测定法确定LUAD和肺癌细胞系中的表达。此外，使用细胞生长曲线、集落形成、Transwell和伤口愈合测定法检查对癌细胞增殖和迁移的功能。
在本研究中，我们发现LUAD中升高，其高表达与LUAD患者不良的临床病理特征和不良预后相关。此外，我们的结果表明，的表达与免疫细胞浸润和免疫调节呈正相关。有趣的是，不同的免疫细胞浸润影响LUAD的预后。在功能测定中，的缺失显著抑制了LUAD的癌细胞生长和迁移。从机制上讲，我们发现DNA甲基化/TMPO-AS1/let-7b-5p轴介导了LUAD中 的高表达。TMPO-AS1的缺失和let-7b-5p的过表达可导致LUAD细胞中表达降低。此外，我们发现TMPO-AS1与LUAD中的呈正相关，但与let-7b-5p表达呈负相关。
我们的研究结果阐明了DNA甲基化/TMPO-AS1/let-7b-5p轴介导了的高表达，这可能被视为预测LUAD预后的生物标志物。
