A-to-I-edited miR-1251-5p restrains tumor growth and metastasis in lung adenocarcinoma through regulating TCF7-mediated Wnt signaling pathway

作者：Shuhua Xu, Zhou Guoping, Qiyu He, Junning Ding, Xiaoli Liu, Youshuang Cheng, Yaqing Shen · 发表于：Discover Oncology · 年份：2024 · DOI：10.1007/s12672-024-01462-7 · 被引用次数：8 · 研究领域：RNA regulation and disease、Cancer-related molecular mechanisms research、RNA Research and Splicing

BACKGROUND: RNA editing from A (adenine nucleotide) to I (hypoxanthine nucleotide) mediated by ADARs has attracted more and more attention as an important post-transcriptional processing method. This research investigates the regulatory mechanism of A-to-I-edited miR-1251-5p in lung adenocarcinoma (LUAD). METHODS: RT-qPCR, Western blot, and Immunohistochemistry assays measured miRNA and gene expression. Colony formation, CCK-8, Transwell, Wound-healing, and Animal assays were used to determine MiRNA function. Luciferase reporter assay tested miRNA downstream target. RESULTS: ADAR1 increased the A-to-I editing efficiency of miR-1251-5p in LUAD cells. In comparison to the unedited wild-type form, edited miR-1251-5p exhibits a marked inhibition of tumor growth and metastasis in LUAD. Moreover, knockdown of TCF7 also exhibits tumor inhibitory effect in LUAD development. Mechanically, edited miR-1251-5p inactivates Wnt signaling pathway by inhibiting TCF7, MYC, and CCND1 expression. CONCLUSION: Compared with original miR-1251-5p, edited miR-1251-5p has stronger anti-cancer effect on LUAD development through inactivating Wnt signaling pathway by inhibiting TCF7.