Abstract

Despite ovarian cancer (OC) represents the leading cause of death in gynecology, however, current understanding of the molecular machinery governing initiation, development and recurrence of the tumor is still limited. Particularly, lack of specific biomarkers defining the complex states of OC limits effective diagnosis and prognosis and, subsequently, hinders appropriate therapy strategies for OC patients. MicroRNA (miR) are small non-coding, regulatory RNA molecules which have critical functions in tumor biology, and which have been functionally grouped into tumor suppressive and tumor promoting miR. miR-1 has been described operating as a tumor suppressor which attenuates proliferation and progression in divers solid cancer entities. Currently, there are no data available concerning miR-1 functionality in progression of OC, particularly, in regard to its potentialas a biomarker for OC diagnosis and treatment. Therefore, the present study examined miR-1 expression levels in established OC cell lines as well as in tissue samples from primary and relapsed OC patients to get a first understanding of putative miR-1 properties in OC progression. Notably, we found miR-1 in OC cell lines was linked to higher cell growth rates. Moreover, analysis of patient samples revealed miR-1 levels in relapsed tumors appeared being up-regulated compared to primary tumors. The findings of our preliminary study (1) may suggest a novel role of miR-1 in OC as a promotor of cancer progression or (2) exhibit a dysregulation of miR-1 functions by a so far unknown disruption of miR-1 regulatory cascades.

Highlights

  • Ovarian cancer (OC) is the leading cause of death among all gynecological malignancies [1]

  • The OC cell lines UWB1.289, TOV-112D, and TOV-21G - all purchased from the American Type Culture Collection (Manassas, VA, USA) - were propagated in RPMI (Biochrom)/MEGM (Lonza, Basel, Switzerland) 1:1 media mixture containing 3% fetal calf serum and 0.065% gentamicin (UWB 1.289) and MCDB105/Medium 199 (Biochrom) mixture containing 15% fetal calf serum and 0.125% gentamicin (TOV-112D, TOV-21G)

  • In this study we aimed at analysing expression levels of miR-1 in OC cell lines as well as in OC tissue samples

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Summary

Introduction

Ovarian cancer (OC) is the leading cause of death among all gynecological malignancies [1]. The advanced stage at the time of diagnosis is defined by a lack of specific symptoms and explained by the absence of appropriate screening tests. Despite achievements in both surgical treatment and the development of new drugs the 5-year survival rate remains very low [2]. Even though OC represents the most lethal cancer in gynecological oncology, very little is known about the molecular machinery governing tumor development and progression. Current studies have identified dysregulated miR expression pattern in various malignancies and, pointed to miR being exceedingly involved in tumor initiation and progression [5, 6]. Recent studies showed miR-1 linked to central mechanisms in tumor biology, e.g. suppression of tumor growth, epithelial-mesenchymal transition, and cell motility [9,10,11], and from these properties it follows that miR-1 belongs to the miR group of tumor suppressors

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