Glioblastoma cancer cells select specific miR-20a pulse frequency for proliferation

ELSI FERRO; SZISCHIK CANDELA; BOSIA CARLA; ALEJANDRA C VENTURA

Heidelberg

Simposio; Biological oscillators: design, mechanism, function; 2022

EMBL

Many gene regulatory pathways are now recognized to function by exploiting pulsatile signals. In these circuits, signal oscillations must occur at specific rates and amplitudes for the desired gene response to be achieved. Specifically, it has been highlighted that microRNAs (miRNAs) can repress their target genes by acting in a pulsatile fashion and that alteration of pulse features may lead cells to aberrant conditions.MiR-20a is known for affecting the invasiveness and viability of glioblastoma cancer cells, including the human U87 cell line. Indeed, miR-20a targets a key transcription factor that regulates the cell cycle, E2F1. Interestingly, E2F1 expression has been observed to pulse coherently with cell cycle phases.We hereby aim to study the oscillatory action of miR-20a on E2F1 function by means of mathematical modelling and optogenetics. Cells will be engineered for endogenous miR-20a expression to be inducible by blue light. Variable spatial and temporal light patterns are provided by a programmable Arduino platform. Light pulses will be applied to cells in order to generate oscillating miRNA expression. Upon variation of the input frequency and amplitude, temporal E2F1 expression will be monitored along with the cell cycle progression and cell viability, and compared to theoretical predictions. We suggest that this response may present optimal features for a given pulse frequency and amplitude, features that are lost if such input parameter requirements are not met. Thus, U87 cancer cell proliferation and invasiveness may be subject to a mechanism of frequency preference.