The role of the tumor suppressor microRNA-1 in ovarian cancer

Background: Even though ovarian cancer (OC) represents the most lethal cancer in gynecologic oncology, an unsatisfactory characterization of the underlying cellular mechanisms primarily prevents development of promising future approaches for diagnosis, prognosis and treatment benefit. In this study we examined the role of the tumor suppressor microRNA-1 (miR-1) in OC cells and OC tumor samples to evaluate miR-1 as a putative biomarker.

Materials and methods: miR-1 levels were detected by quantitative RT-PCR applying total RNA preparations from OC cell lines and tumor samples. For in vitro modulation of miR-1 expression, a miR-1 encoding overexpression vector was cloned and applied in subsequent transfection experiments. miR-1 functionality in OC cell lines was assessed by cell growth kinetics.

Results: In OC cell lines, surprinsingly, higher miR-1 levels were linked to higher cell growth rates. Subsequently, experimental upregulation of miR-1 failed to significantly alter cellular growth compared to control cells. Further analysis of OC patients samples (1) revealed no significant differences between healthy and malignant ovary tissue samples, and (2) showed increased miR-1 levels in relapsed tumors compared to primary tumor tissue.

Conclusion: miR-1 has been characterized as an anti-proliferative and anti-metastatic tumor suppressor in several solid cancer entities. This study exhibited that OC cell growth was not affected by high levels of miR-1, which points to a so far unknown dysregulation of miR-1 dependent signaling and/or effector cascades. Despite the disordered functionality of miR-1 in OC cells, however, increased expression of miR-1 during OC progression may serve as biomarker for tumor relapse.