Try to imagine that what is happening within our cells is a sort of ‘symphony’. The music is complex, performed by thousands of players who need to be directed. The tune that cells play is determined by small segments of DNA—genes.
Coding genes are copied out by messenger RNAs (mRNAs) to produce the musicians of our cell orchestra—the proteins. Yet the genes coding proteins are only a small part of the story. The majority of genes do not code for any proteins, but play an important role in conducting ‘cell symphonies’ by producing so-called non-coding RNAs.
A recently discovered class of non-coding RNAs called microRNAs has a crucial part in directing what tune our protein orchestra plays. MicroRNAs are small, about 1% of the length of normal coding mRNAs, but mighty, because they regulate the amount of proteins produced in the cell. A single microRNA can control hundreds of different mRNAs, and the 700 microRNAs in the human genome might regulate as many as half of our coding genes. They are like ‘conductors’ of protein orchestras.
microRNAs regulate some of the most basic processes in cells such as multiplication and, above all, determining what type of cell a developing cell ultimately becomes. Thus it is not surprising that they seem to be central to the initiation and progression of cancer. A tumour can be regarded as tissue in which cells ‘lose their identity’—become malignant—and start to grow in an uncontrolled or inappropriate manner instead of developing into their predestined cell type. The proteins in cancer cells interfere with normal cell development and cause the cells to ‘play out of tune’.
Researchers around the world are now trying to understand the functions of microRNAs in cancer and investigate their possible application as treatments. My research group at the Department of Genetics and Molecular Biology, Sapienza University of Rome, is interested in the role of microRNAs in a type of blood cancer called acute myeloid leukaemia. Acute myeloid leukaemia is the most common acute leukaemia in adults and is typically fatal within weeks or months if left untreated. It affects a group of blood cells called myeloid cells, which normally develop into mature blood cells such as red blood cells, white blood cells and platelets. Blood cells are produced daily from stem cells in our bone marrow—the spongy tissue inside bones. Acute myeloid leukaemia occurs when these cells become stuck at an immature stage and fail to develop into functional mature blood cells. The immature cells accumulate until they outnumber normal cells in the blood and bone marrow.
Some types of leukaemia can be cured with specific drugs that nudge the immature leukaemic cells into developing to normal functional cells. One of these drugs is a form of vitamin A called retinoic acid. My team is currently doing research on a subtype of acute myeloid leukaemia in which leukemic cells develop into normal white blood cells when treated with retinoic acid promotes. Most importantly, retinoic acid produces complete clinical remission in patients with this particular type of leukaemia. By analysing changes in microRNA levels during treatment with retinoic acid, we have identified the specific ‘microRNAs conductors’ that make sure the protein musicians stick to the correct score.
We are now concentrating on testing the potential of these microRNAs to promote normal cell development in the types of acute myeloid leukaemia that do not respond to retinoic acid treatment —unfortunately the majority. Our findings indicate that microRNAs re-programme malignant leukaemic cells into a more normal state: these tiny molecules ‘conduct’ the protein orchestra in cancer cells. We are testing whether microRNAs will be able to affect the type of music that cells play and turn cancer cell ‘noise’ into the soothing sound of normal cells.
Hopefully, by controlling the action of these micro-cell conductors we will be able to affect the type of music that cells play and prevent them from playing ‘out of tune’.
