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

Abstract

Abstract 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.

Keywords

• A-to-I RNA editing
• miR-1251-5p
• Lung adenocarcinoma
• TCF7
• Wnt signaling