Effect of MT2A on apoptosis and proliferation in HL60 cells

Abstract

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.

Metallothionein 2A with Antioxidant and Antitumor Activity Is Upregulated by Caffeic Acid Phenethyl Ester in Human Bladder Carcinoma Cells

“…MTs have been found to be associated with human cancers [ 40 , 41 ]. Reports have illustrated that MT2A is the modulator of cell proliferation and apoptosis in vitro and in vivo [ 42 , 43 ]. Results from in situ, in vitro, and in vivo studies have suggested that MT2A is an antitumor gene in gastric and colorectal cancers [ 11 , 43 , 44 ].…”

Human Infrapatellar Fat Pad Mesenchymal Stem Cell-Derived Extracellular Vesicles Inhibit Fibroblast Proliferation by Regulating MT2A to Reduce Knee Arthrofibrosis

“…Using transcriptomic sequencing, we screened metallothionein 2A (MT2A), a potential target gene of IPFSC-EVs, for its ability to inhibit knee arthrofibrosis. Studies have shown that MT2A plays an important role in regulating cell proliferation and inflammatory responses [24][25][26][27]. Therefore, exploring the effects of IPFSC-EVs on fibroblast proliferation in the inflammatory environment and the role of MT2A in this process is expected to provide new intervention targets for treating fibrotic diseases in clinical practice.…”