Knockdown of STAU1 inhibits inflammation and autophagy in in vitro chronic obstructive pulmonary disease model by regulating AMPK-mTOR signaling pathway.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, airway obstruction, and lung damage, often triggered by cigarette smoke. Dysregulated autophagy and inflammation are key contributors to its progression. Although double-stranded RNA-binding protein Staufen homolog 1 (STAU1), a multifunctional protein primarily involved in mRNA transport and localization, is identified as a potential biomarker, its role in COPD pathogenesis remains unclear. This study investigates the effects of STAU1 knockdown on inflammation and autophagy in an in vitro COPD model. We found that STAU1 expression was significantly elevated in the in vitro COPD model. Knockdown of STAU1 led to a marked reduction in inflammation in cigarette smoke extract (CSE)-induced non-tumorigenic human bronchial epithelial cells (BEAS-2B). Additionally, STAU1 knockdown suppressed autophagy in CSE-induced BEAS-2B cells. Mechanistically, it inhibited the activation of the adenosine monophosphate-activated protein kinase-mechanistic target of rapamycin (AMPK/mTOR) pathway. In summary, STAU1 knockdown inhibits inflammation and autophagy by modulating the AMPK/mTOR axis. Targeting STAU1 could provide new avenues for the treatment of COPD.