IGF2BP1 facilitates non-small cell lung cancer progression by regulating the KIF2A-mediated Wnt/β-catenin pathway

• Published in: Functional & integrative genomics Vol. 24; no. 1; p. 4
• Main Authors: Sun, Ming, Wang, Ling, Ge, Lei, Xu, Daojun, Zhang, Renquan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2024; Springer Nature B.V
• Subjects: Animal Genetics and Genomics; Apoptosis; beta Catenin - genetics; beta Catenin - metabolism; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Carcinoma, Non-Small-Cell Lung - metabolism; Cell Biology; Cell Line, Tumor; Cell Proliferation - genetics; Cell viability; family; Flow cytometry; Gene Expression Regulation, Neoplastic; genomics; Humans; Immunohistochemistry; Immunoprecipitation; insulin-like growth factor II; Invasiveness; Kinesin; Kinesins - genetics; Kinesins - metabolism; Life Sciences; Lung cancer; lung neoplasms; Lung Neoplasms - pathology; Microbial Genetics and Genomics; MicroRNAs; mRNA; neoplasm progression; Non-small cell lung carcinoma; Original Article; Plant Genetics and Genomics; precipitin tests; quantitative polymerase chain reaction; RNA; RNA, Messenger; RNA-binding protein; Small cell lung carcinoma; Western blotting; Wnt protein; Wnt Signaling Pathway - genetics; β-Catenin; IGF2BP; Wnt/β-catenin signaling pathway; Gene regulation; Non-small cell lung cancer
• ISSN: 1438-793X; 1438-7948; 1438-7948
• DOI: 10.1007/s10142-023-01275-x

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are crucially implicated in the cancer progression. The current study intends to excavate and clarify the mechanisms of the key IGF2BPs in non-small cell lung cancer (NSCLC). The expression of IGF2BPs and kinesin family member 2A (KIF2A) was examined using immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot in NSCLC tissue samples or cell lines. NSCLC cell viability was examined using a cell counting kit-8 assay. Cell apoptotic rate was assessed using flow cytometry analysis. The migration and invasion of H1299 cells were subject to scratch test and Transwell assays, respectively. Starbase 2.0 was used to detect the downstream factors of the IGF2BP1 protein. The binding of IGF2BP with KIF2A was detected using RNA binding protein immunoprecipitation assays. Ki-67 immunohistochemistry assay and TUNEL assays were applied for the evaluation of proliferation and apoptosis in vivo, respectively. IGF2BP1 was upregulated in NSCLC tissue samples and cells. Functionally, IGF2BP1 overexpression promoted the proliferative ability, migration, and invasiveness of H1299 cells, while inhibiting cell apoptosis in vitro. In vivo studies revealed that overexpression of IGF2BP1 promoted tumor growth of NSCLC. Mechanistically, IGF2BP1 was involved in KIF2A mRNA stabilization. KIF2A exerted the same functions as IGF2BP1 via the Wnt/β-catenin signaling. In conclusion, IGF2BP1 enhances NSCLC malignant progression by stabilizing KIF2A to modulate the Wnt/β-catenin pathway.