AKT family and miRNAs expression in IL-۲-induced CD۴+T cells

Objective(s): Study of non-coding RNAs is considerable to elucidate principal biological questions or design new therapeutic strategies. miRNAs are a group of non-coding RNAs that their functions in PI۳K/AKT signaling and apoptosis pathways after T cell activation is not entirely clear. Herein, miRNAs expression and their putative targets in the mentioned pathways were studied in the activated CD۴+T cells. Materials and Methods: Herein, proliferation rate and IL-۲ secretion were measured in treated and untreated cells by IL-۲. Putative targets of up-regulated miRNAs were predicted by bioinformatics approaches in the apoptotic and PI۳K/AKT signaling pathways. Then the expression of two putative targets was evaluated by quantitative RT-PCR.  Results: Proliferation rate of treated cells by IL-۲ increased in a dose- and time- dependent manner. Naive and activated CD۴+T cells  induced by different dose of IL-۲ secreted abundant amounts of IL-۲. Also, in IL-۲ un-induced cells (IL-۲ depleted cells) after ۳ days, decrease of proliferation has been shown. In silico analysis predicted putative targets of up-regulated miRNAs such as AKT۱, AKT۳ and apoptotic genes in the activated cells induced or un-induced by IL-۲. Decrease of AKT۳ was shown by Q-RT-PCR as a potential target of miRNAs overexpressed in IL-۲ depleted cells. But there was no significant difference in AKT۱ expression in two cell groups. Conclusion:  Our analysis suggests that decrease of AKT۳ was likely controlled via up-regulation of specific miRNAs in IL-۲ depleted cells. Also it seems that miRNAs play role in induction of different apoptosis pathways in IL-۲ induced and un-induced cells.

Keywords:

AKT۳ , IL-۲ induction , In silico analysis , miRNAs