Cancer stem cells (CSCs), a rare population in any type of cancers, including colon cancer, are tumorigenic. It has been thought that CSCs are responsible for cancer recurrence, metastasis, and drug resistance. Isolating CSCs in colon cancers is challenging, and thus the molecular mechanism regulating the self-renewing and differentiation of CSCs remains unknown. We cultured DLD-1 cells, one of types of cells derived from colon cancers, in serum-free medium to obtain spheroid cells. These cells possessed the characteristics of CSCs, with the expression of CD133, CD166, Lgr5, and ALDH1, higher capacities of chemo-resistance, migration, invasion, and tumorigenicity in vitro and in vivo than the adherent DLD-1 cells. Krüppel-like factor 4 (KLF4) is essential factor for maintaining self-renewal of adult and embryonic stem cells. It has been used to induce pluripotent stem cells (iPS) from somatic cells. Since KLF4 is expressed in colon cancer cells, we investigated its role in spheroid cells isolated from DLD-1 cells and found that KLF4 was overexpressed only in spheroid cells and reducing the expression of KLF4 by short-hairpin RNA significantly decreased the capacities of these cells to resist the chemicals, migrate, invade, and generate tumors in vitro and in vivo. The spheroid cells with reduced KLF4 expression also had decreased expression of CSCs markers and mesenchymal markers. Taken together, culturing DLD-1 cells in serum-free medium enriches CSCs and the expression of KLF4 is essential for the characteristics of CSCs in DLD-1; thus KLF4 can be a potential therapeutic target for treating colon cancer.
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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