Written by Tori Tucker
Our understanding in cancer biology goes beyond the simplified teachings of the classic “Central Dogma” (DNA → RNA → Protein). Non-coding regions of the genome were once thought as “junk DNA”, but scientists have found that non-coding genes such as microRNAs (miRs) serve an important role in the cell.
In the cell, the nucleus acts as the headquarter in which DNA (the boss) resides. After shuffling through tedious paperwork (cell signals), DNA gives rise to two key workers: mRNA and miRs. mRNAs are the “overachievers” that want to make proteins. However, miRs want to prevent the mRNA workers from making protein product. A checks-and-balances system is needed between mRNA and miRs to keep cells healthy. Dysregulation of miRs can lead to diseases such as cancer when there are too many or too few of them.
Professor Irene Pedersen of the University of California, Irvine is an expert in the field of miRs and studies their regulatory role in cancer, namely in Leukemia. In an interview with Professor Pedersen, she comments on how we need to “look at the microRNA in the pathogenesis of Leukemia because there is a whole new layer of regulation that we have thrown out in the past.”
Professor Pedersen has involved herself in cancer research because “we have all been touched by cancer through family or friends and cancer has become if not the first, but the second killer in our society.”
In one particular study, Professor Pedersen examines the role of miR-155 in targeting SHIP, a protein that prevents cells from dividing rapidly and causing cancer. In the clinic, patients with lymphoma were studied to understand proliferation of lymphoid B cells. Patients who had a type of B cell lymphoma non-GC (germinal centre) had a lower survival rate. After close examination it was understood that non-GC patients had an increase in miR-155 expression that lead to the suppression of SHIP. It was found that miR-155 binds to mRNA of SHIP and causes no protein expression of SHIP.
The major discovery was that miRs are actively involved in cancer and could potentially be targeted with a drug to instead decrease miR production or suppress miRs by an antagonist. Professor Pedersen states that “we can use a specific pathway in our cells to target miR in order to bypass going into the immune cells because we need a good immune response. We can take advantage of tumor environment by using for instance, the acidic environment of a tumor, to deliver an anti-miR that specifically inhibits miRs in that tumor.”
Professor Pedersen also explains the first promising therapeutic in miR treatment against diseases outside of cancer. “Hepatitis C, which affects the liver, is very rich in miR-122 which forms a circular structure that makes it very efficient at being transcribed. miR-122 has caused liver cells to proliferate into Hepatitis C. The anti-miR-122 drug is promising because all drugs pass through the liver and upon taking anti-miR-122, it is guaranteed to go to the liver. However, the challenge is how [the drug] may affect other parts of the body.”
References:
1. Pedersen, Irene M., Dennis Otero, Elaine Kao, Ana V. Miletic, Christoffer Hother, Elisabeth Ralfkiaer, Robert Rickert, Kirsten Gronbaek, and Michael David. 2009. Onco-miR-155 Targets SHIP1 to Promote TNFalpha-dependent Growth of B Cell Lymphomas. EMBO Molecular Medicine.