miR-30d suppresses proliferation and invasiveness of pancreatic cancer by targeting the SOX4/PI3K-AKT axis and predicts poor outcome
Xiaodong Xu, Ke Zong, Xinxing Wang, Dongwei Dou, Pengwei Lv, Zhe Zhang, Hongwen Li
Abstract
Aberrant expression of miR-30d is associated with the development and progression of several human cancers. However, its biological roles and underlying mechanisms in pancreatic cancer are largely unknown. The expression of miR-30d in pancreatic cancer was evaluated in public databases and further valuated by real-time quantitative PCR, western blot, and immunohistochemistry in a cohort of pancreatic cancer patients. The role of miR-30d in the proliferation and metastasis of pancreatic cancer cells was determined using in vitro and in vivo assays. Bioinformatics analyses were performed to examine potential target genes of miR-30d. Luciferase reporter assay and functional rescue experiments were used to elucidate the mechanisms of miR-30d. miR-30d was found frequently decreased in pancreatic cancer compared with nontumor tissues, and downregulation of miR-30d predicted poor prognosis and early relapse of pancreatic cancer patients. Overexpression of miR-30d significantly repressed the growth and metastasis of pancreatic cancer cells both in vitro and in vivo. Bioinformatics analyses identified sex-determining region Y-box 4 (SOX4) as a target gene of miR-30d. Mechanically, miR-30d exerted its tumor suppressive effect by directly targeting SOX4, which caused inhibition of the PI3K-AKT signaling pathway. Overexpression of SOX4 partially antagonized the inhibitory effects of miR-30d. Our study demonstrated that dysregulation of the miR-30d/SOX4/PI3K-AKT axis promotes the development and progression of pancreatic cancer. These findings suggest miR-30d as a promising and reliable therapeutic target for pancreatic cancer.