A long noncoding RNA AB073614 promotes tumorigenesis and predicts poor prognosis in ovarian cancer - PubMed (original) (raw)

A long noncoding RNA AB073614 promotes tumorigenesis and predicts poor prognosis in ovarian cancer

Zhongping Cheng et al. Oncotarget. 2015.

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.

Keywords: AB073614; RNAi; lincRNA; ovarian cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no competing financial interests.

Figures

Figure 1

Figure 1. Screen of OC specific LncRNA in GEO database

LncRNA AB073614 was consistently over-expressed in OC tissue compared to the normal tissue in both of GSE18521 (A) and GSE38666 (B).

Figure 2

Figure 2. LncRNA AB073614 expression in human ovarian cancer tissues

A. Relative expression of AB073614 in OC tissues (n = 75) compared with corresponding non-tumor tissues (n = 75). AB073614 expression was examined by qPCR and normalized to GAPDH expression. Results are presented as the fold-change in tumor tissues relative to normal tissues. B. LncRNA AB073614 expression was classified into two groups, according the expression level in OC tissues. C. The correlation between AB073614 expression and prognosis. 5 year overall survival was analyzed by Kaplan-Meier survival curve. D. The receiver operating characteristic (ROC) curve for prognosis prediction of patients using AB073614 level. The area under curve (AUC) was shown in the plots.

Figure 3

Figure 3. Knockdown AB073614 inhibits OC cells proliferation and invasion in vitro

A. Expression of lncRNA AB073614 in human ovarian epithelial cell line (HOEpiC) and five OC cell lines as determined by qRT-PCR. B. Knockdown efficiency was determined by qRT-PCR in HO-8910 and OVCAR3 cells. Knockdown AB073614 in HO-8910 and OVCAR3 cells significantly reduced their proliferative capacities, as determined by cell number counting assay C. and colony formation assay D. Knockdown AB073614 in HO-8910 and OVCAR3 cells resulted in cell arrest in G1 phase of cell cycle E. and a dramatic increase of apoptosis F. Invasion and metastasis capacities determined by Transwell assays G.

Figure 4

Figure 4. Knockdown AB073614 inhibits OC cells proliferation in vivo

OVCAR3 cells transfected with Si-AB073614 or Si-NC were subcutaneously inoculated into nude mice (6 per group). A. The tumor size was monitored every three days. B. Mice were sacrificed and the tumors were isolated after 33 days. C. Transplanted tumors with H&E staining and PCNA immunostaining. D. The expression of MMP-2 and MMP-9 in xenograft from the nude mice was determined by western blot.

Figure 5

Figure 5. Mechanisms of LncRNA AB073614 exerts its function

Signal pathway and key moderators in tumor progression were determined by western blotting in HO-8910 A, C. and OVCAR3 cells B, D. Left panel, representative results of western blot; right panal, protein levels relative to GAPDH. Data were presented as the mean value from three independent experiments ± S.D. **P < 0.01, **P < 0.001.

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