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KMID : 1094720230280010192
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Biotechnology and Bioprocess Engineering
2023 Volume.28 No. 1 p.192 ~ p.202
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Cyclic AMP Responsive Element Binding Protein 3-like 4/AarF Domain Containing Kinase 5 Axis Facilitates Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells by Modulating the TGFβ Pathway
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Cheng Ai
Tenghao Rong
Zhengyu Chen
Wang Shen
Kaili Huang
Qiang Li
Jing Xiong
Wen Li
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Abstract
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Cyclic AMP responsive element binding protein 3-like 4 (CREB3L4) has been reported as a transcription factor showing high expression in various cancers, whereas the mechanism of CREB3L4 in lung adenocarcinoma (LUAD) progression remains unclear yet. Expression levels of CREB3L4 and its downstream target gene AarF Domain Containing Kinase 5 (ADCK5) in LUAD tissues were analyzed by bioinformatics methods and were detected by real-time quantitative polymerase chain reaction at cellular level. The signaling pathways in which the downregulated ADCK5 enriched were analyzed via Gene Set Enrichment Analysis. The regulatory relationship between CREB3L4 and ADCK5 was identified by ChIP and dual luciferase reporter assay. CCK-8 and colony formation assays were utilized to evaluate LUAD cell proliferation. Transwell was utilized to measure migration and invasion of LUAD cells. Western blot was employed to check expression changes of CREB3L4, ADCK5, TGFβ pathway proteins and Epithelial-Mesenchymal Transition related proteins. Compared with paracancer tissues, CREB3L4 and ADCK5 were highly expressed in LUAD tissues, while silencing CREB3L4 could dramatically hinder invasion, proliferation and migration of LUAD cells. ADCK5 was the downstream target gene of CREB3L4, and CREB3L4 promoted the transcription of ADCK5. ADCK5 was markedly enriched in the TGFβ pathway, which stimulated the malignant development of LUAD cells by activating this pathway. In addition, the rescue assay verified that CREB3L4 regulated the TGFβ pathway by activating ADCK5, thereby accelerating LUAD cell malignant phenotypes. This study revealed the mechanism of CREB3L4/ADCK5 axis facilitating malignant phenotypes of LUAD cells, and bred new insights into the LUAD treatment.
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KEYWORD
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Cyclic AMP responsive element binding protein 3-like 4, AarF Domain Containing Kinase 5, TGFβ pathway, lung adenocarcinoma
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