FOXM1-induced miR-552 expression contributes to pancreatic cancer progression by targeting multiple tumor suppressor genes

Abstract

Dysregulation of microRNAs (miRNAs) plays important roles during carcinogenesis. Forkhead box M1 (FOXM1), a well-known oncogenic transcription factor, has been implicated in the progression of multiple cancer types. To find out FOXM1-induced abnormal miRNAs in pancreatic cancer, we analyzed TCGA database and figured out miR-552 as the most relevant miRNA with FOXM1. Molecular experimental results demonstrated that FOXM1 transcriptionally activated miR-552 expression by directly binding to the promoter region of miR-552. In a pancreatic cancer tissue microarray, miR-552 expression was positively correlated with FOXM1 and high expression of miR-552 could predict poor patient outcome. Functionally, overexpression of miR-552 promoted pancreatic cancer cell migration and inhibition of miR-552 attenuated this phenotype. The inhibitory effect on cell migration caused by FOXM1 knockdown could be restored by exogenous expression of miR-552. By informatics analysis, we identified three tumor suppressor genes: DACH1, PCDH10 and SMAD4, all of which were negatively associated with FOXM1 and validated as functionally relevant targets of miR-552. Taken together, our findings provide a new FOXM1-miR-552-DACH1/PCDH10/SMAD4 axis to regulate pancreatic cancer cell progression and new opportunities for therapeutic intervention against this disease.

Upregulated NORAD is implicated in apoptosis, inflammation, and oxidative stress in ulcerative colitis through the nuclear factor-κappaB signaling

“…Previous reports discovered that miR-552-3p played different functions in different diseases. It was reported that miR-552-3p exerted a promoting role in pancreatic cancer [32], gastric cancer [33], and osteosarcoma [34]. Moreover, miR-552-3p could decrease LDL-C in high fat-fed mice [35] and ameliorate hepatic glycolipid metabolism disorder in high fat-high fructose diet-fed mice [36].…”

The Clinical Significance of Forkhead Box M1 in Esophageal Squamous Cell Carcinoma Tissues: A Study Based on In-house Immunohistochemistry, RNA-sequencing, and Data Mining

“…Liu et al observed that FOXM1 plays a regulatory role in tumor proliferation, invasion, chemotherapy resistance, and genomic mutation by regulating downstream ovarian cancer-related genes (44). In a study focus on pancreatic cancer, Wang et al thought that upregulated FOXM1 will activate the production of miRNA-552 and in uence the expression of DACH1, PCDH10, and SMAD4, which promotes the development of pancreatic cancer (45). Moreover, the transcriptional regulation of FOXM1 has also been reported in head and neck cancer, prostatic cancer, breast cancer, hepatocellular carcinoma, and other cancers ( 46),( 47), ( 48), (49).…”

Defects of endoscopic biopsy in the diagnosis of periampullary carcinoma and recommendations for diagnosis and treatment: a retrospective study before and after surgery

“…In recent years, there are emerging possible adjuvant strategies to prolong postoperative survival time. Targeting the YAP-autophagy circuit and the FOXM1-miR-552-DACH1/PCDH10/SMAD4 axis may offer new opportunities for therapeutic intervention against PAC ( 30 , 31 ). In addition, leflunomide plus gemcitabine has demonstrated inhibition of the growth of pancreatic ductal adenocarcinoma ( 32 ).…”