The FTO/miR‐181b‐3p/ARL5B signaling pathway regulates cell migration and invasion in breast cancer

Background N6‐methyladenosine (m6A) RNA modification has been demonstrated to be a significant regulatory process in the progression of various tumors, including breast cancer. Fat mass and obesity‐associated (FTO) enzyme, initially known as the obesity‐related protein, is the first identified m6A demethylase. However, the relationship between FTO and breast cancer remains controversial. In this study, we aimed to elucidate the role and clinical significance of FTO in breast cancer and to explore the underlying mechanism. Methods We first investigated the expression of FTO in breast cancer cell lines and tissues by quantitative reverse transcription‐PCR (qRT‐PCR), Western blotting, and immunohistochemistry. Wound healing assay and Transwell assay were performed to determine the migration and invasion abilities of SKBR3 and MDA‐MB453 cells with either knockdown or overexpression of FTO. RNA sequencing (RNA‐seq) was conducted to decipher the downstream targets of FTO. qRT‐PCR, luciferase reporter assay, and Western blotting were employed to confirm the existence of the FTO/miR‐181b‐3p/ARL5B axis. The biological function of ADP ribosylation factor like GTPase 5B (ARL5B) in breast cancer cells was evaluated by wound healing assay and Transwell invasion assay. Results High FTO expression was observed in human epidermal growth factor receptor 2 (HER2)‐positive breast cancer, predicting advanced progression (tumor size [P