miR‑92a represses the viability and migration of nerve cells in Hirschsprung's disease by regulating the KLF4/PI3K/AKT pathway

Autor: Chun‑Yi Ji, Miao‑Xian Yuan, Li‑Jian Chen, Hong‑Qiang Gao, Tian Zhang, Qiang Yin
Rok vydání: 2022
Předmět:
Zdroj: Acta neurobiologiae experimentalis. 82(3)
ISSN: 1689-0035
Popis: Hirschsprung’s disease (HSCR) is an intestinal disease caused by defects in neural crest cell migration, proliferation, differentiation, and survival. Many reports have proposed that miRNA dysregulation is related to the occurrence of HSCR. However, the roles and mechanisms of miRNAs have not been thoroughly studied. The levels of miR‑92a and KLF4 were examined using qRT‑PCR and immunohistochemistry, respectively. Cell viability, migration and apoptosis were evaluated by MTT, Transwell and flow cytometry assays, respectively. A dual‑luciferase reporter assay was employed to verify the binding relationship between miR‑92a and KLF4. Levels of PI3K/AKT signals were further determined by western blot assay. Herein, elevated expression of miR‑92a and reduced expression of KLF4 were found in HSCR tissues, and their expression patterns were negatively correlated. Overexpression of miR‑92a inhibited cell viability and migration but enhanced cell apoptosis. However, overexpression of KLF4 had the opposite effects. Mechanistically, KLF4 was a target of miR‑92a and it negatively affected biological functions by activating PI3K/AKT signaling. These results proved that miR‑92a inhibited the proliferation and metastasis of nerve cells by regulating the KLF4/PI3K/AKT axis.
Databáze: OpenAIRE