York University researchers have identified a genetic process that may allow ovarian cancer to resist chemotherapy.
York University researchers have zeroed in on a genetic process that may allow ovarian cancer to resist chemotherapy.
Researchers in the York University Faculty of Science & Engineering studied a tiny strand of our genetic makeup known as a microRNA (miRNA), involved in the regulation of gene expression. Cancer occurs when gene regulation goes haywire.
For many years, DNA and proteins have been viewed as the real movers and shakers in genomic studies, with RNA seen as little more than a messenger that shuttles information between the two. In fact, miRNA was considered relatively unimportant less than a decade ago; that is no longer the case. MiRNA seems to stifle the production of proteins exclusively — a function opposite that of its better-known relative, messenger RNA, or mRNA, which translates instructions from genes to create proteins. MiRNA attaches to a piece of mRNA – which is the master template for building a protein, thereby acting as a signal to prevent translation of the mRNA into a protein. The “silencing” of proteins by miRNAs can be a good or a bad thing, depending on the circumstances.
“Ovarian cancer is a very deadly disease because it’s hard to detect,” says biology professor Chun Peng, who co-authored the study. “By the time it’s diagnosed, usually it is in its late stages. And by that point there’s really no way to treat the disease.” “Even when the disease is discovered in its early stages, chemotherapy doesn’t always work,” she says.
Peng was among a team of researchers that discovered a receptor, ALK7 (activin receptor-like kinase 7), that induces cell-death in epithelial ovarian cancer cells. They have now discerned that miRNA 376c targets this crucial receptor, inhibiting its expression and allowing ovarian cancer cells to thrive.
“Our evidence suggests that miRNA 376c is crucial to determining how a patient will respond to a chemotherapeutic agent,” says Peng. “It allows cancer cells to survive by targeting the very process that kills them off,” she says.
In examining tumors taken from patients who were non-responsive to chemotherapy, researchers found a higher expression of miRNA 376c and a much lower expression of ALK7. Peng believes that this research is a step towards being able to make chemotherapy drugs more effective in the treatment of the disease.
“Further study is needed, but ultimately if we can introduce anti-microRNAs that would lower the level of those microRNAs that make cancer cells resistant to chemotherapeutic drugs, we will be able to make chemotherapy more effective against ovarian cancer,” Peng says.
She urges women to educate themselves about the risk factors and symptoms of the disease. For more information, visit http://www.ovariancanada.org.
Peng is a world expert in the area of ovarian cancer and the molecular basis of complications in pregnancy. Her research on chemoresistance has also contributed to knowledge and prediction of pre-eclampsia, a pregnancy disorder that is a leading cause of maternal and perinatal complications and death.
The article, MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance, was published in the Journal of Cell Science.
The study’s lead author, Gang Ye, is a Research Associate in Peng’s lab. Several trainees in Peng’s lab, as well as scientists in Toronto’s Sunnybrook Research Institute and in China, also participated in the project.
The research was supported by an operating grant from the Canadian Institutes of Health Research (CIHR) and a mid-career award to Peng from the Ontario Women’s Health Council/CIHR. Ye was supported in part by a Fellowship from the Toronto Ovarian Cancer Research Network.
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1/Xu G, Zhou H, Wang Q, et. al. Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and down-regulation of Xiap in normal and malignant ovarian epithelial cell lines. Mol Cancer Res. 2006 Apr;4(4):235-46. PubMed PMID: 16603637.
2/Ye G, Fu G, Cui S, et. al. MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance. J Cell Sci. 2011 Feb 1;124(Pt 3):359-68. Epub 2011 Jan 11. PubMed PMID: 21224400.
Source: York U researchers uncovering how ovarian cancer resists chemotherapy, Press Release, York University, March 2, 2011.