National Cancer Institute (NCI) figures suggest that 140,250 new cases of colorectal cancer could be diagnosed in the United States in 2018.
Among all the known risk factors for this cancer, the Centers for Disease Control and Prevention (CDC) name a family history of colon cancer, an unhealthful diet, and obesity.
Lately, researchers are becoming more and more interested in whether variations in the bacterial populations of our guts impact the regulation of gene expression and facilitate the development of colon cancer.
A new study from the University of Minnesota in Twin Cities, which has now been published in the journal mSystems, suggests that there is a link between the composition of a person’s gut microbiome and the emergence of colon cancer.
The researchers, led by Ran Blekhman, believe that certain gut bacteria influence the activity of some types of microRNA (miRNA), which are non-coding molecules that help to regulate gene expression.
Such an interaction, they surmise, may lead to dysregulations at cell level that are characteristic of colon cancer.
“This is a correlation, but it is still very exciting, because if we see a causal effect, you can think of ways to manipulate the microRNA in the tumors by changing the microbiome, and that could potentially be used as a cancer therapy.”
Ran Blekhman
Are gut bacteria-miRNA interactions key?
The notion that gut bacteria could potentially play a role in colon cancer, the fact that — according to recent research — miRNA dysreguations can facilitate tumor growth, and the belief that these non-coding molecules can interact with gut bacteria all influenced the team’s decision to begin their recent investigation.
“We wanted to look at all of these things together,” Blekhman goes on to say, “to see if there is any interaction between the host microRNA and the microbiome in the context of colon cancer.”
The researchers started by assessing colon cancer tumor, as well as colon tissue samples collected from human patients during a former study conducted at the University of Minnesota. In total, they analyzed 88 samples from 44 people.
Next, Blekhman and team used miRNA sequencing to determine the presence of these molecules in the tumor and tissue samples. They then traced associations between particular microbiota compositions and levels of miRNA expression in the patient samples.
They revealed that many types of miRNA molecule were diferentially expressed in colon tumors, compared with healthy colon tissue. Moreover, these differences appeared to be consistent with the bacterial abundance found in tumors.
Gut bacteria previously linked to colon cancer, such as Fusobacterium and Providencia, were linked to the expression of miRNAs — such as miRNA-182, miRNA-503, and miRNA17-92 — that may play a role in the production of glycans, carbohydrate compounds that have been tied to the development of cancer.
Hope for better colon cancer therapies
“We found networks of microbes that are dependent on the microRNA,” Blekhman explains. “Then, we specifically investigated the microbes that have been previously linked to cancer, and we identified all of the microRNAs that are correlated with the abundance of these microbes.”
Although the researchers are happy about their recent findings, they note that, so far, they have only observed correlations, and more work will be necessary to prove a causal relationship between the miRNA-gut bacteria interaction and the development of colon cancer.
“This is an exciting result, but for now, we have shown correlation,” cautions Blekhman.
However, the researchers are already attending to the task of identifying the potential underlying mechanisms that would prove causation. “We are currently working to show a direct effect of the microbiome on the microRNA using animal models,” says Blekhman.
If this hypothesis is correct, it could guide researchers in developing treatments that would act on miRNA expression in such a way as to prevent tumor growth.
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