EPN3 plays oncogenic role in non‐small cell lung cancer by activating the JAK1/2‐STAT3 pathway

• Published in: Environmental toxicology Vol. 38; no. 8; pp. 1968 - 1979
• Main Authors: Meng, Jiguang, Zhang, Chunyang, Zhu, Nengyang, Zhang, Caiyun, Liu, Meng, Han, Zhihai, Li, Yongqun
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2023; Wiley Subscription Services, Inc
• Subjects: Adaptor Proteins, Vesicular Transport - genetics; Adaptor Proteins, Vesicular Transport - metabolism; Animals; Apoptosis; Cancer; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cells; EPN3; Flow cytometry; Gene Expression Regulation, Neoplastic; Genomes; Humans; Immunohistochemistry; invasion; JAK1/2‐STAT3 pathway; Janus kinase; Janus Kinase 1 - genetics; Lung - pathology; Lung cancer; Lung Neoplasms - pathology; Mice; Mice, Nude; MicroRNAs - genetics; Non-small cell lung carcinoma; NSCLC; Nucleotide sequence; Patients; Phenotypes; Polymerase chain reaction; Proliferation; Reverse transcription; Small cell lung carcinoma; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Survival; Transcription; Xenotransplantation; EPN3; JAK1/2-STAT3 pathway; apoptosis; NSCLC; invasion
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23822

The effect of Epsin 3 (EPN3) on non‐small cell lung cancer (NSCLC) has not yet been clearly elucidated. This study identified the exact function of EPN3 on NSCLC progression. EPN3 expression in NSCLC patients were analyzed based on the Cancer Genome Atlas database. Kaplan–Meier analysis was implemented to research the effect of EPN3 on patients' survival. EPN3 expression in clinical tissues of 62 NSCLC cases was monitored by real‐time quantitative reverse transcription polymerase chain reaction, immunohistochemistry and Western blot. A549 and H1299 cells were transfected with EPN3 shRNA and treated by RO8191 (20 μM). Proliferation was researched by cell counting kit‐8 and 5‐ethnyl‐2 deoxyuridine assays. Apoptosis was monitored by flow cytometry. Migration and invasion was assessed by Transwell experiment. EPN3 effect on A549 cell in vivo growth was researched using nude mice. RO8191 (200 μg) was intratumoral injected into mice. Immunohistochemistry and Western blot was implemented to monitor protein expression in cells and xenograft tumor tissues. EPN3 was abnormally up‐regulated in NSCLC patients and cells, indicating a lower overall survival. Loss of EPN3 weakened proliferation, migration and invasion, induced apoptosis, and repressed epithelial‐mesenchymal transition in NSCLC cells. Loss of EPN3 inactivated the JAK1/2‐STAT3 pathway in NSCLC cells. RO8191 treatment reversed the inhibition of EPN3 knockdown on the malignant phenotype of NSCLC cells. RO8191 intratumoral injection reversed the suppression of EPN3 silencing on NSCLC cell in vivo growth. EPN3 acted as an oncogene in NSCLC via activating the JAK1/2‐STAT3 pathway. EPN3 may be a promising target for NSCLC treatment.