Abstract
Pancreatic cancer (PC) is a highly aggressive malignancy of the digestive system. Recent studies have indicated that the long noncoding RNA SOX21-AS1 is significantly upregulated in PC tissue samples. This study aims to elucidate the biological role and underlying molecular mechanisms of SOX21-AS1 in PC progression. Quantitative real-time PCR (qRT-PCR) and western blot analyses were employed to assess RNA and protein expression levels, respectively. The subcellular localization of SOX21-AS1 was determined using subcellular fractionation assays. PC cell viability, migratory capacity, and apoptosis were evaluated through CCK-8 assays, wound healing assays, and flow cytometry. Dual-luciferase reporter and RNA pull-down assays were conducted to confirm the interactions between miR-9-3p and either SOX21-AS1 or YOD1. Additionally, a xenograft mouse model was established to investigate the in vivo effects of SOX21-AS1. The findings revealed that SOX21-AS1 is highly expressed in PC tissues and cell lines, with its upregulation correlating with poor patient prognosis. Functional assays demonstrated that knockdown of SOX21-AS1 suppressed PC cell proliferation and migration, induced apoptosis in vitro, and reduced tumor growth in vivo. Mechanistically, SOX21-AS1 competitively interacted with miR-9-3p to upregulate YOD1, consequently activating the TGF-β/Smad signaling pathway. Furthermore, overexpression of YOD1 reversed the tumor-suppressive effects observed after SOX21-AS1 knockdown. In conclusion, SOX21-AS1 promotes PC cell malignancy through the miR-9-3p/YOD1 axis and subsequent activation of TGF-β/Smad signaling.