MiR-195-5p suppresses the proliferation, migration, and invasion of gallbladder cancer cells by targeting FOSL1 and regulating the Wnt/β-catenin pathway.

Background: MicroRNA-messenger RNA (miRNA-mRNA) regulatory networks are essential factors that regulate tumor development and metastasis in various cancers including gallbladder carcinoma (GBC). Here, we identified the miR-195-5p/Fos-like antigen-1 ( FOSL1 ) axis in GBC by bioinformatics analysis and aimed to investigate its role and regulatory mechanism in the development and progression of GBC.
Methods: Bioinformatics analysis was used to construct a miRNA-mRNA regulatory network. Real-time quantitative polymerase chain reaction (qRT-PCR), western blot, and dual luciferase reporter assays confirmed that miR-195-5p targets FOSL1 in GBC. Cell Counting Kit-8 (CCK-8), wound healing, transwell, flow cytometry assays, western blotting, and immunofluorescence were used to detect the biological effects of the miR-195-5p / FOSL1 regulatory axis and the Wnt / β-catenin signaling pathway on the proliferation, migration, invasion, and cell cycle of GBC cells. A nude mouse tumorigenesis model was constructed to verify the role of miR-195-5p in vivo .
Results: Bioinformatics analysis and qRT-PCR confirmed that the miR-195-5p / FOSL1 regulatory axis was closely related to GBC cells. Overexpression of miR-195-5p inhibited the proliferation, migration, and invasion of GBC cells, and the cells were blocked in the G0/G1 phase. Dual luciferase reporter gene assays and western blot analysis showed that FOSL1 is targeted by miR-195-5p . The recovery experiment showed that miR-195-5p can inhibit cell proliferation, migration, invasion, and increase of cells in the G0/G1 phase, and the overexpression of FOSL1 could restore this effect by regulating the Wnt/β-catenin signaling pathway. Finally, we confirmed that miR-195-5p inhibited the growth of transplanted tumors in vivo .
Conclusions: The overexpression of miR-195-5p inhibits the proliferation and metastasis of GBC cells by directly targeting FOSL1 and regulating the Wnt/β-catenin signaling pathway.
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3685/coif). All authors report that this work was supported by grants from the National Natural Science Foundation of China (Nos. 30671987 and 8180102403), PhD Start-up Fund of Natural Science Foundation of Guangdong Province (No. 2015A030310377) and National Key Clinical Discipline. The authors have no other conflicts of interest to declare.
(2022 Annals of Translational Medicine. All rights reserved.)