Abstract
Long noncoding RNA (lncRNA) profiles in ovarian cancer (OC) remain largely unknown. In the present study, we screened AB073614 as a new candidate lncRNA which promotes development of OC, in two independent datasets (GSE18521 and GSE38666) from the Gene Expression Omnibus (GEO). The level of AB073614 was then detected in 75 paired OC tissues and adjacent normal tissues by qRT-PCR. Results showed that AB073614 expression was significantly up-regulated in 85.3% (64/75) cancerous tissues compared with normal counterparts (P < 0.01). Further, the 5-year overall survival (OS) in OC patients with high expression of AB073614 was inferior to that with low expression (17.2 months vs 30.0 months, P = 0.0025). To investigate the functional role of AB073614, AB073614 siRNA was transfected into OC cell lines. Knockdown of AB073614 expression significantly inhibited cell proliferation and invasion, resulted in cell arrest in G1 phase of cell cycle and a dramatic increase of apoptosis, both in HO-8910 and OVCAR3 cells. In vivo experiment also revealed that knockdown AB073614 inhibited OVCAR3 cells proliferation. Finally, western blot assays indicated that lncRNA AB073614 may exert its function by targeting ERK1/2 and AKT-mediated signaling pathway. In conclusion, our study suggests that lncRNA AB073614 acts as a functional oncogene in OC development.
Highlights
Ovarian cancer (OC) is the most lethal gynecological cancer and a common cause of cancer-related deaths in women worldwide [1,2,3]
AB073614 expression was significantly up-regulated in 85.3% (64/75) cancerous tissues compared with normal counterparts (P < 0.01) (Figure 2A)
Kaplan-Meier analysis and log-rank test were used to evaluate the correlation of AB073614 expression and prognosis, as shown in Figure 2C, the 5-year overall survival (OS) in OC patients with high expression of AB073614 was inferior to that with low expression (mean 17.2 months vs 30.0 months, P = 0.0025)
Summary
Ovarian cancer (OC) is the most lethal gynecological cancer and a common cause of cancer-related deaths in women worldwide [1,2,3]. Despite advances in surgery and chemotherapy, the overall survival of OC patients remains unsatisfactory, with a five-year survival rate of only 30% [4]. Patients with this malignancy have an extremely poor prognosis due to late clinical presentation, subtle symptomatology, and rapid disease progression. In order to develop better preventive and diagnostic approaches, as well as more effective treatment modalities, a deep understanding is required of the molecular mechanisms implicated in the complex process of ovarian carcinogenesis. Emerging evidences indicate that lncRNAs may play complex and extensive roles in promoting the development and progression of cancer [6, 7]
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