Abstract
The roles of long non-coding RNAs (lncRNAs), a class of long non-protein-coding RNAs, in the tumorigenesis of ovarian epithelial cells remain unknown. In this study, we discovered that the expression of long intergenic non-coding RNA 1088 (LINC01088) was clearly reduced in benign epithelial ovarian tumor tissues compared to matched normal ovarian tissues. This was shown by global cDNA gene chip scanning and real-time qPCR, and validated in 42 clinical specimens. Furthermore, we found that LINC01088 inhibited the growth of ovarian cancer xenografts in nude mice. Correlation analysis between LINC01088 and mircoRNAs (miRNAs) conducted using primary clinical samples and RNA co-precipitation experiments revealed that miR-24-1-5p was one of the targets of LINC01088. Overexpression of miR-24-1-5p facilitated cell proliferation both in vitro and in vivo, however, LINC01088 could partially reverse the cell proliferation induced by miR-24-1-5p. Finally, we demonstrated that p21 activated kinase 4 (PAK4) was one of the downstream key targets of miR-24-1-5p by luciferase reporter assay and Western blotting; and our results showed a remarkable decrease in cell proliferation after overexpression of PAK4. We conclude that LINC01088 might function as a tumor suppressor, inhibiting the tumorigenesis of ovarian epithelial cells through LINC01088/ miR-24-1-5p/ PAK4 axis.
Highlights
Ovarian neoplasm is one of the most common gynecological tumors
To identify the genes involved in tumorigenesis of ovarian epithelial cells, we conducted the global cDNA gene chip scanning and found that the expression of long intergenic non-coding RNA 1088 (LINC01088) in benign epithelial ovarian tumor tissues was reduced in comparison to normal ovarian epithelial tissues
NAs involved in tumorigenesis of ovarian epithelial cells, we analysed lincRNA expression in 3 benign epithelial ovarian tumor tissue specimens and 3 normal ovarian epithelial tissue specimens using gene chip scanning
Summary
Ovarian neoplasm is one of the most common gynecological tumors. The benign ovarian tumors can be cured by excision. Epithelial ovarian cancer is among the most lethal gynecological malignancies, with the five-year survival rate of less than 30%1. Long non-coding RNAs (LncRNAs) and mircoRNAs (miRNAs) are two classes of common non-protein-coding RNAs. LncRNAs are transcripts longer than 200 nucleotides[2] that are involved in various biological processes, such as transcription regulation, cell proliferation and differentiation[3]. MiRNAs are composed of approximately 18 to 22 nucleotides, and they play a role in biological processes like cell proliferation, apoptosis and cell differentiation[8,9]. It has been confirmed that aberrant expression of miRNAs is closely related to tumor progression, and to tumorigenesis and neoplasm metastasis[10,11]. Further exploration indicated that miR-24-1-5p was a target of LINC01088, which provided experimental support for the role of LINC01088 in effective suppression of the occurrence of epithelial ovarian cancers
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