It is known that chronic inflammation in the gut increases the risk of colon cancer by as much as 500%. Therefore, the genetic basis and mechanism of cancer proliferation in these cases are highly desirable targets. Now, a study from researchers at Duke University shows that a biomarker in the cellular machinery could not only serve as an early warning of colon cancer, it could also potentially be harnessed to counteract advanced forms of the disease. The team state that their findings show how colon cancer development is intricately linked to a specific microRNA that dictates how cells divide. The opensource study is published in the journal Cell Stem Cell.
Previous studies show that cells usually divide symmetrically, producing two identical daughter cells. However, there are prokaryotic and eukaryotic cells that can divide asymmetrically, giving rise to daughter cells with different characteristics. Cancer stem cells undergo both symmetric and asymmetric division. Recent studies show that microRNA called miR-34a gives cancer stem cells the odd ability to divide asymmetrically. This process has been shown to control the cancerous stem cell population and generate a diverse set of cells. While researchers knew that miR-34a was responsible for this ability, nobody knew where it came from, because normal, healthy colon stem cells don’t asymmetrically divide and don’t need this microRNA. The current study investigates if there is a mutation unique to cancer stem cells, or a hidden role for the microRNA in normal physiology.
The current study deleted miR-34a from the genetic code of mice and observed that the mice’s tissues became inflamed. Results show that without any miR-34a, their stem cells quickly grew out of control and formed many tumour-like structures. Data findings show that miR-34a is an immune response which is triggered to act when the gut becomes inflamed, where it forces the process of asymmetrical division, helping to control normal stem cell populations.
Results show that even in the early stages of tumour growth, the microRNA remains active to keep the cancer stem cell population down. The lab observed that as the cancer progresses however, its cells develop mutations that enable shutting off miR-34a, causing cells to divide into flexible hybrids that can revert back into stem cells if needed. The group state that it’s this flexibility that makes late-stage cancers so difficult to eradicate. They go on to explain that these microRNAs are the good guys who only show up when things go wrong and when they are silenced in late-stage cancer, the cancer becomes much worse.
The team surmise that their findings suggest that a test to look for elevated levels of miR-34a could be an early warning system to catch cancers. They go on to add that they are trying to get the cancer cells to express miR-34a again as this should stop the tumour cells from gaining the flexibility to revert back to stem cells and allow doctors to wipe them. For the future, the researchers state that clinical trials are currently trying to do just this in multiple cancer types, however, this is the first study that has shown that it might also work for colon cancer.
Source: Duke University