Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China.
Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China.
Lung Cancer. 2024 Sep;195:107918. doi: 10.1016/j.lungcan.2024.107918. Epub 2024 Aug 5.
Tigger transposable element-derived 1 (TIGD1) expression and its underlying functions and regulatory mechanisms in lung adenocarcinoma (LUAD) remain unknown. Therefore, we intended to explore the expression, potential functions, and regulatory mechanisms of TIGD1 in LUAD.
TIGD1 expression in LUAD tissues was determined by immunohistochemistry analysis of a tissue microarray. Functional experiments were conducted to determine how TIGD1 affects LUAD tumorigenesis and metastasis. The molecular mechanisms by which TIGD1 induces LUAD progression were determined.
TIGD1 was upregulated in LUAD tissues and was related to lymph node metastases. TIGD1 knockdown suppressed LUAD cell proliferation, migration, and invasion, while promoted cell apoptosis. Furthermore, decreased metastatic nodules were observed in the TIGD1 knockdown mouse metastasis model. Moreover, microarray analysis was performed to determine the potential downstream genes of TIGD1 in LUAD. Hallmark pathway analysis revealed that the downstream genes of TIGD1 were involved in epithelial-mesenchymal transition (EMT). Western blotting confirmed that vimentin and TWIST was downregulated in TIGD1 knockdown cells, while E-cadherin was upregulated. Ingenuity pathway and hallmark pathway analyses revealed that TIGD1 regulated the interleukin-6 signaling pathway and related gene members. Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay indicated that downregulation of TIGD1 decreased interleukin-6 and CXCL1 expression. TIGD1 expression was negatively correlated with immune infiltration in LUAD. The upstream microRNA of TIGD1 was predicted, and subsequent luciferase reporter gene experiments confirmed the interactions between miR-137 and TIGD1. The expression of miR-137 was significantly downregulated in LUAD tissues and miR-137 suppressed the proliferation, migration, and invasion of LUAD cells, partially through negatively regulating the expression of TIGD1.
Our findings suggest that TIGD1, which was regulated by miR-137, contributed to LUAD progression by promoting cell proliferation, migration, invasion, and EMT and suppressing cell apoptosis.
Tigger 转座子衍生 1（TIGD1）在肺腺癌（LUAD）中的表达及其潜在功能和调控机制尚不清楚。因此，我们旨在探讨 TIGD1 在 LUAD 中的表达、潜在功能和调控机制。
通过组织微阵列的免疫组织化学分析来确定 LUAD 组织中的 TIGD1 表达。进行功能实验以确定 TIGD1 如何影响 LUAD 的肿瘤发生和转移。确定 TIGD1 诱导 LUAD 进展的分子机制。
TIGD1 在 LUAD 组织中上调，并与淋巴结转移有关。TIGD1 敲低抑制 LUAD 细胞增殖、迁移和侵袭，同时促进细胞凋亡。此外，在 TIGD1 敲低的小鼠转移模型中观察到转移结节减少。此外，进行了微阵列分析以确定 LUAD 中 TIGD1 的潜在下游基因。标志性途径分析显示，TIGD1 的下游基因参与上皮-间充质转化（EMT）。Western blot 证实，TIGD1 敲低细胞中波形蛋白和 TWIST 下调，而 E-钙粘蛋白上调。Ingenuity 途径和标志性途径分析显示，TIGD1 调节白细胞介素-6 信号通路和相关基因成员。Western blot、定量实时聚合酶链反应、酶联免疫吸附试验表明，下调 TIGD1 可降低白细胞介素-6 和 CXCL1 的表达。TIGD1 的表达与 LUAD 中的免疫浸润呈负相关。预测了 TIGD1 的上游 microRNA，随后的荧光素酶报告基因实验证实了 miR-137 与 TIGD1 之间的相互作用。miR-137 在 LUAD 组织中的表达明显下调，miR-137 抑制 LUAD 细胞的增殖、迁移和侵袭，部分通过负调控 TIGD1 的表达。
我们的研究结果表明，受 miR-137 调控的 TIGD1 通过促进细胞增殖、迁移、侵袭和 EMT 并抑制细胞凋亡来促进 LUAD 的进展。
