Abstract

RAS protein activator like-1 (RASAL1) exists in numerous human tissues and has been commonly demonstrated to act as a tumor suppressor in several cancers. This study aimed to identify the functional characteristics of RASAL1 in ovarian adenocarcinoma and a potential mechanism of action. We analyzed RASAL1 gene expression in ovarian adenocarcinoma samples and normal samples gained from the GEO and Oncomine databases respectively. Then the relationship between RASAL1 expression and overall survival (OS) was assessed using the Kaplan-Meier method. Furthermore, the biological effect of RASAL1 in ovarian adenocarcinoma cell lines was assessed by Quantitative real time-PCR (qRT-PCR), Cell Counting Kit-8 (CCK-8), western blot, wound healing and transwell assay. The statistical analysis showed patients with higher RASAL1 expression correlated with worse OS. The in vitro assays suggested knockdown of RASAL1 could inhibit cell proliferation, cell invasion and migration of ovarian adenocarcinoma. Moreover, the key proteins in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathway were also decreased in ovarian adenocarcinoma cells with RASAL1 silencing. These findings provide promising evidence that RASAL1 may be not only a powerful biomarker but also an effective therapeutic target of ovarian adenocarcinoma.

Highlights

  • Ovarian cancer is ranked as the fifth most common type of cancer in women and the fourth most common cause of cancer death in women worldwide

  • Given that silencing of RAS protein activator like-1 (RASAL1) inhibits the proliferation of ovarian adenocarcinoma cell line HEY, we investigated cell migration and invasion in HEY transfected with si-RASAL1 using a wound healing assay and a transwell assay

  • To determine whether RASAL1 manipulates ovarian adenocarcinoma progression, we evaluated the activation of key signaling proteins in the MAPK signaling pathway, including p-ERK and p-mitogenactivated protein kinase (MEK)

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Summary

Introduction

Ovarian cancer is ranked as the fifth most common type of cancer in women and the fourth most common cause of cancer death in women worldwide. The American Cancer Society estimates over 20 000 new cases of ovarian cancer will be diagnosed each year and almost 15 500 women died of this disease [1, 2]. Most ovarian cancer cases are diagnosed as advanced stages (III and IV) and the 5-year survival is

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