Involvement of HuR in the serum starvation induced autophagy through regulation of Beclin1 in breast cancer cell-line, MCF-7.

ABSTRACT

Starvation is a cellular stress that induces autophagy, a conserved cellular self-digestion mechanism that allows cells to degrade and recycle damaged proteins and organelles. The present study illustrated that during serum deprivation, Beclin1, a crucial gene that is essential for autophagosome formation in autophagy, gets controlled post-transcriptionally in breast cancer cell-line MCF-7. RNA affinity chromatography and co-immunoprecipitation confirmed the association of HuR with 3'-UTR of beclin1 mRNA. After cytosolic translocation, HuR enhances beclin1 protein synthesis in response to serum starvation by enhancing the association of beclin1 mRNA to the polysomes. Partial silencing of HuR resulted in reduction of beclin1 expression both at mRNA and protein levels, which in turn decreased starvation-induced autophagic flux. Thus, in conclusion, fine-tuning of beclin1 gene expression at post-transcriptional level by HuR is one of the key regulatory mechanisms of starvation induced autophagy in breast cancer cell-line, MCF-7.