One of the things a cancer patient can hear from their doctor is “recurrence.” Modern cancer therapies are actually quite effective at inducing remission in many patients. Cancer is a persistent disease, however, and many patients experience recurrence. In ovarian cancer, after surgery and platinum/paclitaxel combination therapy, there is still more than a fifty percent chance of recurrence after five years. Clearly, the standard treatment needs improving.
An effort has been established to identify as many biomarkers as possible for this purpose. Biomarkers are proteins or molecules that indicate a disease is present, or how aggressive a disease might be. They may also be used as drug targets. An increased understanding of biomarkers can give patients and doctors a considerable head start in treatment and increase the chances of survival.
A team from the Beijing Center for Physical and Chemical Analysis hypothesized it could use microRNA (miRNA) as a biomarker. miRNAs have already been shown to act as tumor suppressors or promoters in many cancers and are a target for many biomarker studies. The miRNA miR-454, in particular, was of interest to them. It has been linked to pro-tumor activities in some cancers, but in others has shown anti-tumor effects. They decided to investigate miR-454’s effects on ovarian cancer.
They began by examining miR-454 in ovarian cancer patients compared to healthy patients. miR-454 was significantly elevated in ovarian cancer patients. They also noticed a clear association of miR-454 levels with the pathological stages of ovarian cancer with earlier stages showing a much higher level of miR-454 compared to later stages.
In vitro studies found that miR-454 seemed to negatively affect both the growth and invasiveness of ovarian cancer cell lines. The team identified that miR-454 appeared to inactivate Akt/mTOR and Wnt/β-catenin signaling pathways. Both pathways are critical for cancer formation and progression, and suppression of either is usually a sign of a tumor suppressor.
A scan of potential binding sites for the miR-454 found the E2F6 mRNA would be a prime target. In vitro experimentation confirmed this observation. Further investigation found E2F6 overexpression in ovarian cancer cells to have a pro-tumor growth effect. Combined with ovarian cancer tissue showing higher levels of E2F6 compared to healthy tissue, their observations solidify E2F6 as an oncogene.
The use of miRNA as a potential biomarker, or even treatment path, is rapidly coming into focus as a legitimate idea. Many miRNAs have already been found to correlate with anti-tumor or pro-tumor effects, miR-454 included. This study links miR-454 to the suppression of the oncogene E2F6, as well as the inactivation of Akt/mTOR and Wnt/β-catenin signaling pathways in ovarian cancer. These observations make it a prime target as a biomarker. The team concludes, “Collectively, our data support the view that miR-454 functions as a tumor suppressor in ovarian cancer.”