Abstract

BackgroundOvarian cancer is a common type of gynecological malignancies, and is the fifth leading cause of cancer-related death in women in the United States. MiR-429 and KIAA0101 have been found to be involved in several human malignancies, respectively. However, the role of miR-429 and KIAA0101, and the correlation between them during development of epithelial ovarian cancer (EOC) remain to be investigated.MethodsThe expression of KIAA0101 in EOC tissues and cells was measured by Quantitative real-time PCR, western blot, and immunochemistry. Cell proliferation assay, colony formation assay, and transwell assay was performed to assess the role of miR-429 and KIAA0101 in regulation of proliferation, migration, and chemoresistance of EOC cells. Luciferase assay was used to test the Wnt/β-catenin signaling activity in response to depletion of KIAA0101 and overexpression of miR-429.ResultsWe found that KIAA0101 was upregulated in metastatic EOC tissues, compared to primary EOC tissues, and KIAA0101 was required for the migration activity and chemoresistance of EOC cells by enhancing Wnt/β-catenin signaling. Furthermore, we revealed KIAA0101 is direct target of miR-429. Similar to knockdown of KIAA0101, overexpression of miR-429 reduced invasion and chemoresistance of EOC cells. Co-transfection of KIAA0101 partially abrogates the inhibitory effects on invasion and chemoresistance in EOC cells.ConclusionsKIAA0101, a target gene of miR-429, was upregulated in the metastatic EOC tissues, and enhanced the migration activity and chemoresistance of EOC cells. Both miR-429 and KIAA0101 may represent the potential therapeutic targets of EOC.

Highlights

  • Ovarian cancer is a common type of gynecological malignancies, and is the fifth leading cause of cancer-related death in women in the United States

  • We found that compared to those in normal ovarian epithelial tissues, the levels of KIAA0101 expression were significantly higher in epithelial ovarian cancer (EOC) tissues (Fig. 1a, p < 0.001)

  • In this study, we investigated the role of miR-429 and its target gene KIAA0101 in regulation of migration and chemoresistance of EOC cell lines, SKOV3 and COV644

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Summary

Introduction

Ovarian cancer is a common type of gynecological malignancies, and is the fifth leading cause of cancer-related death in women in the United States. MiR-429 and KIAA0101 have been found to be involved in several human malignancies, respectively. The role of miR-429 and KIAA0101, and the correlation between them during development of epithelial ovarian cancer (EOC) remain to be investigated. EOC is a common type of gynecological malignancy that accounts for the majority of gynecologic cancer-related, mainly because of the highly metastatic capacity of EOC cells [3]. In recent years, accumulating evidence has demonstrated that miRNAs are involved in cancer development by acting as oncogenes or tumor suppressors [9, 10]. MiR-429, a member of the miR-200 family of miRNAs, has been reported to inhibit invasion in gastric cancer [11], colorectal carcinoma [12], breast cancer [13], and oral squamous cell

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