Abstract. Thioredoxin binding protein (thioredoxin-interacting protein, TXNIP), known as vitamin D3 increase protein 1, has been identified as a tumor suppressor in various cancers such as pancreatic, breast, lung and thyroid cancer. However, the role of TXNIP in hepatocellular carcinoma cell proliferation and apoptosis remains unknown. In this study, we first used qRT-PCR, western blotting and immunohistochemistry to compare the expression of TXNIP between hepatocellular carcinoma tissues and tumor-adjacent normal liver tissues. In vitro, we explored the role of TXNIP in hepatocellular carcinoma progression via transfection of the pcDNA-3.1-TXNIP plasmid into SMMC7221 cells. Our results showed that the expression of TXNIP was significantly decreased in hepatocellular carcinoma tissues. Moreover, TXNIP over expression inhibited hepatocellular carcinoma cell proliferation and induced apoptosis by triggering mitochondrial-mediated ROS generation and activating MAPK pathways. This study provides insight into the molecular mechanisms of TXNIP overexpression in liver cancer cell survival and apoptosis and indicated that TXNIP may be a novel promising agent for liver cancer treatment.
microRNAs (miRNAs) have been proved to be involved in many events of tumor development and progression, including cell proliferation, cell apoptosis, and cell cycle arrest. However, the potential role of miR-144-3p in pancreatic cancer (PC) remains elusive. In this study, we demonstrated that miR-144-3p was decreased in PC tissues and PANC-1 cells, whereas proline-rich protein 11 (PRR11) was remarkably increased. miR-144-3p mimics were discovered to inhibit cell proliferation by arresting cells at the S-phase of the cell cycle, and inducing cell apoptosis in PANC-1 cells. The effects of miR-144-3p on cell proliferation and cell apoptosis were reversed after treatment with the miR-144-3p inhibitor. Furthermore, a luciferase activity assay indicated that miR-144-3p directly targeted PRR11 3'-UTR. Moreover, transfection with miR-144-3p mimics inhibited the expression of PRR11. miR-144-3p mimics also upregulated the expression of p-JNK and p-p38, whereas they downregulated the expression of p-ERK. The effects of miR-144-3p on mitogen-activated protein kinase pathway proteins were reversed by the miR-144-3p inhibitor. PRR11 overexpression attenuated the effect of miR-144-3p mimics on cell apoptosis and cell cycle arrest. The expression of caspase-3 was decreased by enhanced PRR11. In summary, our findings indicated that miR-144-3p induced cell cycle arrest and apoptosis in PC by targeting PRR11. Therefore, the targeting of miR-144-3p could serve as a potential therapeutic strategy for the treatment of PC.
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