Long non-coding RNA LINC00152 is up-regulated in ovarian cancer tissues and regulates proliferation and cell cycle of SKOV3 cells.

Abstract

OBJECTIVE\nTo characterize functions of long non-coding RNA (lncRNA) in the progression of epithelial ovarian cancer.\n\n\nPATIENTS AND METHODS\nEpithelial ovarian cancer tissues and matching normal tissues were collected from two individual patients for RNA microarray analysis. Besides, twenty-two ovarian cancer samples and ten healthy ovarian epithelial tissues were collected for Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR). Microarray assay suggested that a list of cancer relating mRNAs and lncRNAs were upregulated. The identified lncRNAs were validated via RT-qPCR, which led to the identification of long intergenic non-protein coding RNA 152 (LINC00152). To determine the function of LINC00152 in ovarian cancer, we knocked down the expression of LINC00152 in epithelial ovarian cancer cell line SKOV3 with small interference RNAs (siRNAs). The effects of LIN00152 on the proliferation and cell cycle were determined by comparing the cell viability of SKOV3 cells with LIN00152 knockdown and the control cells with negative siRNA. The cell viability was assessed using Cell Counting Kit-8 (CCK-8) and flow cytometry assay. RNA microarray assay was used again in control and LINC00152 knockdown SKOV3 cells to identify downstream signaling pathways.\n\n\nRESULTS\nFourteen ovarian cancer relating lncRNAs were identified by RNA microarray assay. Up-regulation of LINC00152 was validated via RT-qPCR. A higher expression of LINC00152 in late cancer stage (III-IV) compared to the early stage tumors was also demonstrated. Inhibition of LINC00152 in SKOV3 cells inhibited cell proliferation and induced cell cycle arrest that involved prolonged G1 phase and shortened S phase. The microarray assay data of SKOV3 cells suggested that Cyclin-Dependent Kinase Inhibitor 1C (CDKN1C) was a potential downstream target of LINC00152.\n\n\nCONCLUSIONS\nLINC00152 is upregulated in epithelial ovarian cancer tissues comparing to normal tissues. Knockdown of LINC00152 expression inhibits cell proliferation and induces cell cycle arrest. LINC00152 possibly interacts with Tumor Necrosis Factor (TNF) signaling pathway. CDKN1C is a potential downstream target of LINC00152.