Autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell’s own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products. It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more-essential processes. Autophagy is an evolutionarily conserved mechanism of cellular self-digestion in which proteins and organelles are degraded through delivery to lysosomes. Defects in this process are implicated in numerous human diseases including cancer.
The most well-known mechanism of autophagy involves the formation of a membrane around a targeted region of the cell, separating the contents from the rest of the cytoplasm. The resultant vesicle then fuses with a lysosome and subsequently degrades the contents.
Starving of Cancer Cells by microRNA-101
Many cancer cells have an increased capacity to carry out activity of autophagy , which give them an unfair advantage over normal cells. Defects in the process have been associated with a number of other health disorders.
Professor Andres H. Lund, principal scientist at the University of Copenhagen and his team has developed a small molecule...
known as microRNA-101 to block this process, and to also shed light on its mechanics. According to them, microRNA-101 can be used specifically to increase the sensitivity of breast cancer cells towards a commonly used treatment.
They identified the tumour suppressive miRNA, miR-101as a potent inhibitor of basal, etoposide- and rapamycin-induced autophagy. Through transcriptome profiling, they identified three unique miR-101 targets e.g. STMN1, RAB5A and ATG4D. siRNA-mediated depletion of these genes phenocopied the effect of miR-101, resulting their involvement in autophagy regulation. Importantly, overexpression of STMN1 could partially rescue cells from miR-101-mediated inhibition of autophagy, indicating a functional importance for this target.
The researchers concluted that breast cancer cells become more sensitive towards treatment with the anti-hormone Tamoxifen, when they turn off the autophagy system. Resistance against tamoxifen is a large problem in the treatment of breast cancer, through microRNA-101.