Tumor suppressive role of miR-33a-5p in pancreatic ductal adenocarcinoma cells by directly targeting RAP2A

Background The suppressive effects of miR-33a-5p have been reported in colorectal cancer and lung cancer. However, the functional role of miR-33a-5p in pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated. Methods The expression of miR-33a-5p was determined using reverse-transcription quantitative PCR (RT-qPCR) in PDAC tissues and cell lines. The association between miR-33a-5p expression and clinical categorical parameters was analyzed by the chi-square test. Cell proliferation was analyzing by Cell Counting Kit -8 (CCK-8) assay. Transwell assay was utilized to assess cell migration and invasion. The interactions between miR-33a-5p and RAP2A were verified by luciferase reporter assay, RT-qPCR, western blot analysis and RNA immunoprecipitation (RIP) assay. Results Here, we observed for the first time that miR-33a-5p expression level was significantly decreased in PDAC tissues and cell lines. There was a significant association between decreased miR-33a-5p expression and TNM stage or lymph node metastasis. Overexpression of miR-33a-5p significantly inhibited SW1990 and PANC-1 cell proliferation, migration and invasion. Knockdown of miR-33a-5p remarkedly promoted cell proliferation, migration and invasion in BxPC-3 and ASPC-1. Mechanistically, RAP2A was confirmed as the target of miR-33a-5p in PDAC cells. Moreover, RAP2A overexpression abolished miR-33a-5p-mediated suppressive effects on SW1990 and PANC-1 cells. Conclusions Taken together, these results suggest that miR-33a-5p exerted tumor suppressive effects on PDAC cells by targeting RAP2A, which might provide a new theoretical basis for the clinical treatment of PDAC.

Automated summary

The study found that miR-33a-5p expression is significantly decreased in PDAC tissues and cell lines, and its downregulation is significantly associated with TNM staging and lymph node metastasis. Overexpression of miR-33a-5p inhibits cell proliferation, migration, and invasion in SW1990 and PANC-1 cells, while knockdown of miR-33a-5p promotes these processes in BxPC-3 and ASPC-1 cells. Additionally, RAP2A was identified as a direct target of miR-33a-5p in PDAC cells, and its overexpression reversed the suppressive effects of miR-33a-5p in SW1990 and PANC-1 cells.