Effect of MT2A on apoptosis and proliferation in HL60 cells.

Although accumulating evidence has revealed that metallothioneins (MTs) and its family member MT2A are strongly linked to the risk of various solid tumors, researches on the occurrence and development of acute myeloid leukemia (AML) have rarely been investigated. Here, we constructed a lentiviral vector with MT2A over-expression and the interfering plasmids with MT2A expression inhibition to study the influence of MT2A on the bioactivities of HL60 cells. After cells were infected with a lentiviral vector containing the MT2A gene, both transcription and translation levels of MT2A were significantly increased in the over-expressed group in comparison with control groups. In vitro experiments, all results demonstrated that cell reproductive capacity was inhibited, but cell apoptosis rate was significantly increased. Together, the expression of apoptosis-related protein Bcl2 was remarkably reduced, while a high expression level of Bax protein was detected. Further experiments revealed that up-regulation of MT2A induced cell apoptosis and promoted G2/M phase arrest. The mechanism may be associated with down-regulated p-IκB-α and cyclinD1 expression and up-regulated IκB-α expression in the nuclear factor-kappaB (NF-κB) pathway. On the contrary, MT2A expression was down-regulated by interfering plasmids. We found that cell proliferative potential was notably increased in the interfering group compared with the negative and untreated group. What's more, MT2A may be closely related to AML cell proliferation and function via the NF-κB signal pathway.

Pan YQ ，Niu M ，Liu SM ，Bao YX ，Yang K ，Ma XB ，He L ，Li YX ，Cao JX ，Zhang X ，Du Y ... -  《International Journal of Medical Sciences》

Metallothionein 2A inhibits NF-κB pathway activation and predicts clinical outcome segregated with TNM stage in gastric cancer patients following radical resection.

Pan Y ，Huang J ，Xing R ，Yin X ，Cui J ，Li W ，Yu J ，Lu Y ... -  《Journal of Translational Medicine》

Epigenetic Upregulation of Metallothionein 2A by Diallyl Trisulfide Enhances Chemosensitivity of Human Gastric Cancer Cells to Docetaxel Through Attenuating NF-κB Activation.

Pan Y ，Lin S ，Xing R ，Zhu M ，Lin B ，Cui J ，Li W ，Gao J ，Shen L ，Zhao Y ，Guo M ，Wang JM ，Huang J ，Lu Y ... -  《-》

Effect of GINS2 on proliferation and apoptosis in leukemic cell line.

Zhang X ，Zhong L ，Liu BZ ，Gao YJ ，Gao YM ，Hu XX ... -  《-》

Overexpression of microRNA-125b inhibits human acute myeloid leukemia cells invasion, proliferation and promotes cells apoptosis by targeting NF-κB signaling pathway.

microRNA-125b has been reported to play an novel biological function in the progression and development of several kinds of leukemia. However, the detail role of miR-125b in acute myeloid leukemia (AML) is remains largely unknown. The present study aimed to investigate the biological role of miR-125b in AML and the potential molecular mechanism involved in this process. Our results showed that overexpression of miR-125b suppressed AML cells proliferation, invasion and promotes cells apoptosis in a dose-dependent manner, while the miR-NC did not show the same effect. In addition, miR-125b induced AML cells G2/M cell cycle arrest in vitro. Overexpression of miR-125b resulted in a significant decrease of the expression of p-IκB-α and inhibition of IκB-α degradation, and the nuclear translocation of NF-κB subunit p65 was abrogated by miR-125b simutaneously. To further verify that miR-125b targeted NF-κB signaling pathway, the NF-κB-regulated downstream genes that were associated with cell cycle arrest and apoptosis was also determined. The results showed that, miR-125b also affect NF-κB-regulated genes expression involved in cell cycle arrest and apoptosis. In conclusion, the present work certificates that miR-125b can significantly inhibit human AML cells invasion, proliferation and promotes cells apoptosis by targeting the NF-κB signaling pathway, and thus it can be viewed as an promising therapeutic target for AML.

Wang Y ，Tang P ，Chen Y ，Chen J ，Ma R ，Sun L ... -  《-》