Nucleus‐localized adiponectin is survival gatekeeper through miR‐214‐mediated AIFM2 regulation

Abstract

Adiponectin secreted from adipocytes into plasma has anti‐aging, anti‐obesity and anti‐inflammation effects. Here, we detected intracellular adiponectin localized in the nuclei of human and mouse pluripotent stem cells, mouse germ cells and some somatic cells. Nucleus‐localized (Nu) adiponectin protein is characterized by an N‐terminal truncated monomer form in a native state, compared with intact multimer forms of cytoplasm‐localized (Cy) adiponectin protein. Doxycycline‐induced over‐expression of ADIPONECTIN caused cell death in human and mouse Nu‐type pluripotent stem cells. Genome‐wide gene expression analysis indicated that apoptosis by ADIPONECTIN over‐expression was induced in accompany with upregulation of AIFM2 and MEG3. Upregulation of AIFM2 and MEG3 and down‐regulation of miR‐214‐3p verified by qPCR analyses after ADIPONECTIN over‐expression indicated that the MEG3/miR‐214/AIFM2 pathway played a role in the apoptotic cell death of pluripotent cells. Adiponectin‐induced cell death was rescued by the treatment with miR‐214‐3p mimic. Global data analysis shows that Nu adiponectin has a role in microRNA‐mediated post‐transcription regulation, cell–cell interactions and chromatin remodeling as a survival gatekeeper.

IMPA2 blocks cervical cancer cell apoptosis and induces paclitaxel resistance through p53-mediated AIFM2 regulation

“…Although we have confirmed the proapoptotic function of AIFM2 in cervical cancer, conflicting data exist on the proapoptotic function of the protein in different diseases [ 18 – 20 ] . By comparing the viability of AIFM2 -silenced cells and control cells, we found that there was no significant difference ( ), indicating that apart from apoptosis, other processes regulated by AIFM2 may also be involved in cervical cancer cell death.…”

The apoptosis‐inducing factor family: Moonlighting proteins in the crosstalk between mitochondria and nuclei

“…This has taken to the proposal of the MEG3‐miR‐214‐AMID pathway regulating the growth of T‐cell lymphoblastic lymphoma and playing a role in apoptotic cell death induced by over accumulation of the nuclear adiponectin hormone, providing potential prognosis markers as well as new potential targets for the treatment of such lymphoma (Table SP1). 89 Despite being initially envisaged as a potential tumour suppressor gene, recent studies appear to indicate that AMID does not seem to be a requirement for normal development and tumour suppression. On the contrary, its pharmacological targeting suggests that its coenzyme Q 10 ‐NAD(P)H pathway rather cooperates to suppress phospholipid peroxidation and ferroptosis 58 .…”