Ovarian cancer has the highest prevalence among gynecological cancers in the world with 200,000 new cases and 150,000 deaths per year. The main problem of this pathology is the late detection leading to the formation of metastases and chemoresistance. In a study published March 21, 2018 in the journal Cell Research, researchers at the Institute of Human Genetics discovered a new mechanism for regulating the expression of the protein Dicer, a mechanism involved in the progression of ovarian cancer. This discovery could allow the setting up of a new therapeutic process as well as that of a prognostic marker.
Micro-RNAs (miRNAs) are small non-coding RNAs with a length of 18 to 22 nucleotides that allow the level of messenger RNAs (mRNA) to be finely regulated. Dicer protein is a key enzyme in the biogenesis of these miRNAs. Decreased expression is often associated with aggressive and invasive cancer and low survival, especially in ovarian cancer. However, the regulation of Dicer’s expression is poorly understood.
Researchers have shown that the NF90 protein, which is capable of binding double-stranded RNA, facilitates the expression of Dicer by blocking the processing of a miRNA, miR-3173, located in the first intron of pre-RNA. They also determined that, surprisingly, miR-3173 targeted the NF90 messenger RNA thus establishing a feedback amplifying loop that controls Dicer expression.
The results indicate in several ovarian cancer cell lines that overexpression of NF90 decreases proliferation and tumor invasion. In addition, the researchers observed, in vivo, that this overexpression greatly reduces the size of the ovarian tumor and the number of metastases. In contrast, overexpression of miR-3173 increases the proliferation of cancer cells and the number of metastases depending on the level of NF90 and Dicer.
Finally, analysis of ovarian tumor samples demonstrated that low expression of NF90 and a high level of miR-3173 were associated with greater tumor aggressiveness (higher tumor grade) and low survival rate in a cohort of women with ovarian cancer.
These findings suggest that by facilitating the expression of Dicer, NF90 could act as a suppressor of ovarian carcinoma and allow the creation of a new therapeutic track mimicking the effect of NF90.