MiR-29 Induces K562 Cell Apoptosis by Down-Regulating FoxM1.

BACKGROUND: Leukemia seriously threatens human life and health. MicroRNAs can regulate cell growth, proliferation, and death. This article investigated the role of miR-29 on regulating leukemia cell growth, proliferation, and apoptosis. MATERIAL AND METHODS: miR-29 and scramble miRNA were transfected to K562 cells. MTT assay, colony formation assay, caspase-3 activity detection, and flow cytometry were applied to test miR-29 effect on cell growth, proliferation, and apoptosis. Western blot was used to detect Forkhead box protein M1 (FoxM1) protein expression. After we transfected miR-29, K562 cells were transfected with FoxM1 siRNA to test cell apoptosis. RESULTS: K562 cell growth and proliferation were inhibited after transfection with miR-29. Apoptosis phenome and caspase-3 activation were observed. FoxM1 level decreased. SiRNA FoxM1 enhanced miR-29-induced K562 cell apoptosis. FoxM1 overexpression suppressed miR-26-induced K562 cell apoptosis. CONCLUSIONS: MiR-29 restrained K562 cell growth and proliferation. MiR-29 induced K562 cell apoptosis through down-regulating FoxM1.

Invasion inhibition by a MEK inhibitor correlates with the actin-based cytoskeleton in lung cancer A549 cells.

Metastasis remains the primary cause of lung cancer. The molecules involved in metastasis may be candidates for new targets in the therapy of lung cancer. The MEK/ERK signaling pathway has been highlighted in a number of studies on invasiveness and metastasis. In this paper, we show that the MEK inhibitor U0126 induces flattened morphology, remodels the actin-based cytoskeleton, and potently inhibits chemotaxis and Matrigel invasion in the human lung cancer A549 cell line. Furthermore, downregulation of ERK by small interfering RNA significantly inhibits the invasion of A549 cells and induces stress fiber formation. Taken together, our findings provide the first evidence that the inhibition of invasion of lung cancer A549 cells by inhibiting MEK/ERK signaling activity is associated with remodeling of the actin cytoskeleton, suggesting a novel link between MEK/ERK signaling-mediated cell invasion and the actin-based cytoskeleton.

A positive feedback loop of p53/miR-19/TP53INP1 modulates pancreatic cancer cell proliferation and apoptosis.

Pancreatic cancer is a common malignancy whose prognosis and treatment of pancreatic cancer is extremely poor, with only 20% of patients reaching two years of survival. Previous findings have shown that the tumor suppressor p53 is involved in the development of various types of cancer, including pancreatic cancer. Additionally, p53 is able to activate TP53INP1 transcription by regulating several phenotypes of cancer cells. Using gain and loss-of-function assays, the aim of the present study was to examine the relationships between miR-19a/b and cancer development as well as potential underlying mechanisms. The results showed that miR-19a/b identified a positive feedback regulation of p53/TP53INP1 axis. Additionally, p53 upregulated the TP53INP1 level in pancreatic cancer cells. However, overexpressed miR-19a/b partially restored the TP53 function in the pancreatic cancer cells while miR-19a/b downregulated TP53INP1 protein by directly targeting 3'UTR of its mRNA at the post-transcriptional level. In addition, the patient tissues identified that the miR-19a/b level in pancreatic cancer tissues was conversely correlated with TP53 and TP53INP1 expression. The results provide evidence for revealing the molecular mechanism involved in the development of pancreatic cancer and may be useful in the identification of new therapeutic targets for pancreatic cancer.

Changes of Th17/Treg cell and related cytokines in pancreatic cancer patients.

To explore the mechanism of Th17 cells and Treg cells in the peripheral blood of patients with pancreatic cancer through analyzing the changes of the related genes and cytokines expression. 40 patients were divided into three groups based on clinical staging, and 20 healthy subjects were treated as normal control. Proportion of Th17 cells and Treg cells were detected by flow cytometry. RORα, RORγt, FoxP3, and CTLA-4 expression in peripheral blood mononuclear cells were detected by RT-PCR. IL-10, IL-23, INF-γ, TGF-ß, and IL-17 cytokine levels in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). The proportion of Th17 cells in peripheral blood of pancreatic cancer patients was lower than that in the normal control, while the proportion of Treg was higher. RORα and RORγt mRNA expression in Th17 cells from pancreatic cancer patients decreased, while FoxP3 and CTLA-4 mRNA expressions in Treg cells increased compared with the normal control. And the correlation analysis revealed that they were significantly correlated with clinical staging. Compared with healthy control, IL-23, IL-17 and INF-γ levels were lower in pancreatic cancer patients, while IL-10 and TGF-ß levels were higher. Following the progression of disease, patients in advanced stage exhibited higher level of IL-10 and TGF-ß, and lower levels of IL-23 and INF-γ. Pancreatic cancer patients exhibited Th17/Treg balance disorders with higher Treg and lower Th17 cells. They affect cytokine IL-10, IL-23, INF-γ, TGF-ß, and IL-17 expression changes mainly through regulating transcription factors such as RORα, RORγt, FoxP3 and CTLA-4, suggesting that Th17/Treg balance disorders plays an important role in the tumorigenesis of pancreatic cancer.