The Regulatory Role of SNORD35A in Pancreatic Cancer Involves the HGF/C-Met Pathway

Pancreatic adenocarcinoma (PAAD) is a type of malignant tumors in the digestive tract. It is extremely aggressive. However, the molecular mechanism of the occurrence and development of pancreatic cancer has not yet been elucidated. New evidence shows that the dysregulation of small nucleolar RNAs (SnoRNAs) plays an important role in tumorigenesis and has a certain connection with tumor stem cells. In this study, the authors screened differentially expressed SnoRNAs in pancreatic cancer, further explored whether the HGF/C-Met pathway is involved in the regulation of SNORD35A in pancreatic cancer stem cells. AffymetrixmiRNA 4.0 and QRT-PCR was used for differential screening of SnoRNA. CCK8, wound healing assay and TransWell chamber were used to detect cell proliferation, migration and invasion. QRT-PCR was used to detect the changes of epithelial - mesenchymal Transition (EMT) related genes of tumors. The authors detected the expression levels of HGF/C-Met pathway and its related proteins by Western blotting. The authors found that SNORD35A is significantly overexpressed in pancreatic cancer. After disturbing the expression of SNORD35A, the epithelial markers increased and the mesenchymal markers decreased during the EMT process. At the same time, down-regulation of SNORD35A inhibited the proliferation, migration and invasion of pancreatic cancer stem cells in cellular level. In nude mouse transplanted tumor models, low expression of SNORD35A reduced tumor growth volume and attenuated its pathological features. Finally, the authors found that silencing SNORD35A reduced the expression levels of C-Met and its phosphorylated proteins. These results suggest that the regulation of SNORD35A on proliferation, migration, invasion and EMT of pancreatic cancer stem cells involves HGF/C-Met signaling pathway. SNORD35A has carcinogenic effects in pancreatic cancer and may become a prognostic biomarker and therapeutic target for pancreatic cancer patients.