关键词: 胰腺导管癌, 单羧酸转运蛋白1, 预后, 转移, miR-124-3p

Abstract: Background and purpose: Monocarboxylate transporter 1 (MCT1) is commonly seen to be significantly overexpressed in cancer tissues that takes charge of transporting the lactate, pyruvate and their derivatives belonging to monocarboxylate in cells. However, the role of MCT1 in pancreatic ductal adenocarcinoma has rarely been described. This study aimed to investigate the expression of MCT1 and its clinicopathological significance. Methods: The tumor tissues from 78 cases of pancreatic ductal adenocarcinoma and the paired normal control tissues were collected. Immunohistochemistry was performed to detect and analyze the expression of MCT1 and its clinicopathological significance. In vitro, pancreatic ductal adenocarcinoma cell lines PANC-1 and Capan-1 were used to analyze the biological role of MCT1 in the proliferation, migration and invasion of cancer cells using clonogenic, wound-healing and Transwell assays. To explore the relevant mechanism by which MCT1 functions in pancreatic cancer cells, miR-124-3p was predicted to be a putative regulatory miRNA. To further confirm the potential regulation, luciferase reporter assay was used. Moreover, both mRNA of MCT1 and miR-124-3p were detected using real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) in additional 51 paired cases of pancreatic ductal adenocarcinoma and their normal controls. Results: The positive expression of MCT1 was mainly located in the cell membrane and cytoplasm and remarkably up-regulated in pancreatic ductal adenocarcinoma tissues compared with paired normal control tissues. Over-expressed MCT1 significantly correlated with differentiation, clinical stage, lymph node metastasis and poor overall prognosis. In vitro, silencing of MCT1 was shown to be able to markedly suppress the proliferation, migration and invasion of PANC-1 and Capan-1 cells. miR-124-3p was identified to be able to negatively regulate MCT1 expression. Conclusion: MCT1 is an oncogene in pancreatic ductal adenocarcinoma, and miR-124-3p can negatively modulate the expression of MCT1 in pancreatic ductal adenocarcinoma.

Key words: Pancreatic ductal adenocarcinoma, Monocarboxylate transporter 1, Prognosis, Metastasis, miR-124-3p