Could these 'molecular switches' stop brain cancer?

It might be possible to change the course of glioblastoma, a very aggressive brain cancer, by manipulating small molecules that switch genes on and off inside cells.

This was the conclusion of a study in which researchers in the United Kingdom and India manipulated gene-regulating molecules known as microRNAs (miRNAs) in "human glioblastoma cells."

In a paper published in the journal Scientific Reports, they report how "overexpression" of two particular miRNAs reduced the ability of the brain cancer cells to invade and multiply.

The findings strengthen the case for using molecular techniques to slow or reverse the progress of glioblastoma — a "devastating disease" with few treatment options — says co-senior study author Dr. Arijit Mukhopadhyay, who researches and lectures in human genetics at the University of Salford in the U.K.

"We observed," he adds, "significant reduction of proliferation and invasion capacity and increased apoptosis [programmed cell death] of cancer cells when we used increased expression of microRNAs as a switch."

Glioblastomas are difficult to treat

Glioblastoma is an aggressive cancer that starts in cells known as astrocytes. These form the tissue that supports the neurons that carry and process information in the brain and spinal cord.

The main reason that the cancer is so aggressive is because astrocytes "reproduce quickly" and the tissue has a rich blood supply. Around 15.4 percent of "all primary brain tumors" are glioblastomas.

Management of glioblastoma, which has "remained stable" for 40 years, usually consists of surgery with radiation and chemotherapy.

But, the tumors can be very difficult to remove with surgery because they have long "tentacles" that can reach into other parts of the brain.

There is hope, however, that recent progress in genetic and molecular techniques will improve the "management and outcome of this devastating tumor."

miRNAs have a role in cancer

miRNAs are small non-coding molecules inside cells that can alter the expression of specific genes. This means, for example, that if the affected gene is one that codes for a protein, a miRNA that silences the gene could stop the cell from making the protein.

The study of miRNAs is a relatively "new and exciting field" with "profound implications" for medicine.

Although there is still a lot to learn about their specific targets and mechanisms of action, we know that miRNAs regulate many genes that control a great number of cell processes and pathways.

Since the first miRNA was discovered 30 years ago in roundworms, researchers have identified more than 2,000 in humans and it is thought that they control around a third of "protein-coding genes" in the human genome.

Studies show that miRNAs have altered "expression profiles" in particular tumors, which suggests that they have a role in cancer.

It has also been demonstrated that miRNAs are likely to be involved in the development of colon cancer through interaction with gut bacteria.

'New candidates for disease management'

In the new study, Dr. Mukhopadhyay and his colleagues investigated a "cluster" of miRNAs that previous work had found to be more weakly expressed in human glioblastoma.

Using a technique called "real-time polymerase chain reaction," they tested the effect of miRNA expression in tumor samples taken from patient biopsies.

They found that they could manipulate two miRNAs — called miR-134 and miR-485-5p — like "molecular switches" to make the cancer cells act more like normal cells.

They note, "Overexpression of miR-134 and miR-485-5p in human glioblastoma cells suppressed invasion and proliferation, respectively."

The authors conclude that the two molecules may have "therapeutic value" that progresses the field "toward better disease management and therapy."

"Adult brain cancers, especially glioblastoma [are] very aggressive with very limited management options. This research opens up newer approaches and candidates for disease management and therapy."

Dr. Arijit Mukhopadhyay