MiR-590 Suppresses Proliferation and Induces Apoptosis in Pancreatic Cancer by Targeting High Mobility Group A2.

BACKGROUND: Pancreatic ductal adenocarcinoma is a common malignancy with high morbidity. MicroRNAs have been demonstrated to be critical posttranscriptional regulators in tumorigenesis. This study aimed to investigate the effect of microRNA-590 on the proliferation and apoptosis of pancreatic ductal adenocarcinoma. MATERIAL AND METHODS: The expression of microRNA-590 and high mobility group AT-hook 2 were examined in clinical pancreatic ductal adenocarcinoma tissues. Pancreatic ductal adenocarcinoma cell line Capan-2 was employed and transfected with microRNA-590 mimics or inhibitor. The correlation between microRNA-590 and high mobility group AT-hook 2 was verified by luciferase reporter assay. Cell viability and apoptosis were detected by MTT and flow cytometry assay. The protein level of high mobility group AT-hook 2, AKT, p-AKT, mTOR, and phosphorylated mTOR were analyzed by Western blotting. RESULTS: MicroRNA-590 was found to be negatively correlated with the expression of high mobility group AT-hook 2 in pancreatic ductal adenocarcinoma tissues. Further studies identified high mobility group AT-hook 2 as a direct target of microRNA-590. Moreover, overexpression of microRNA-590 downregulated expression of high mobility group AT-hook 2, reduced cell viability, and promoted cell apoptosis, while knockdown of miR-590 led to an inverse result. MicroRNA-590 also suppressed the phosphorylation of AKT and mTOR without altering total AKT and mTOR levels. CONCLUSION: Our study indicated that microRNA-590 negatively regulates the expression of high mobility group AT-hook 2 in clinical specimens and in vitro. MicroRNA-590 can inhibit cell proliferation and induce cell apoptosis in pancreatic ductal adenocarcinoma cells. This regulatory effect of microRNA-590 may be associated with AKT signaling pathway. Therefore, microRNA-590 has the potential to be used as a biomarker for predicting the progression of pancreatic ductal adenocarcinoma.

miR-410 acts as an oncogene in colorectal cancer cells by targeting dickkopf-related protein 1 via the Wnt/ß-catenin signaling pathway.

Colorectal cancer (CRC) is a common malignancy with high morbidity. MicroRNAs (miRNAs or miRs) have been demonstrated to be critical post-transcriptional regulators in tumorigenesis. The current study aimed to investigate the effect of miR-410 on the proliferation and metastasis of CRC. The expression of miR-410 was examined in CRC cell lines. SW-480 and HCT-116 CRC cell lines were employed and transfected with miR-410 inhibitor or miR-410 mimics. The association between miR-410 and dickkopf-related protein 1 (DKK-1) was verified by luciferase reporter assay. Cell viability and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Cell migration and invasion capacity were determined by Transwell assay. The protein level of DKK1, ß-catenin and phosphorylated glycogen synthase kinase-3ß (pGSK-3ß) were analyzed by western blotting. miR-410 was revealed to be upregulated in CRC cell lines. Further studies identified DKK-1 as a direct target of miR-410. In addition, knockdown of miR-410 promoted the expression of DKK, inhibited CRC cell proliferation, migration and invasion capacity, and induced cell apoptosis, while overexpression of miR-410 reversed these results. miR-410 silencing also decreased ß-catenin and pGSK-3ß levels. The current study indicated that miR-410 negatively regulates the expression of DKK-1 in vitro. miR-410 promotes malignancy phenotypes in CRC cell lines. This regulatory effect of miR-410 may be associated with the Wnt/ß-catenin signaling pathway. Therefore, miR-410 could be used as a biomarker for predicting the progression of CRC.