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

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.

The Role of Long Non-Coding RNAs in Ovarian Cancer

“…However, the level of lncRNAs expression is associated with disease prognosis, patients' survival, and therapeutic response [14,15] . In addition, their expression has been found to be significantly regulated by estrogen.…”

“…It has been shown to be up-regulated in 85.3% of ovarian cancerous tissues compared with normal counterparts [15] . Besides, patients with high expression of AB073614 had a lower 5-year overall survival in comparison with low expression group.…”

“…Down-regulation of this lncRNA using small interfering RNA (siRNA) strategy in ovarian cancer cell lines considerably reduced cell proliferation and invasion, leading to cell arrest in G1 phase of cell cycle and a remarkable increase in apoptosis. The function of this lncRNA may be exerted through the targeting of extracellular signal-regulated kinase (ERK)1/2 and Protein Kinase B Alpha (PKB, AKT)-mediated signaling pathway [15] .…”

Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer

“…For example, poor prognosis (shorter OS) is associated with high expression of nuclear paraspeckle assembly transcript 1 (NEAT1) [79], ANRIL [63], and AB0736614 in patients with OC [69]. Furthermore, both shorter OS and disease-free survival (DFS) were associated with up-regulated CCAT2 [62] and HOXA11as [66], whereas low expression of GAS5 was associated with shorter OS and DFS in patients with OC [61].…”

Upregulation of long noncoding RNA zinc finger antisense 1 enhances epithelial–mesenchymal transition in vitro and predicts poor prognosis in glioma

“…7 Among them, lncRNAs have acquired extensive attention, recently, as new regulators in many biological processes, such as transcriptional regulation, 8 differentiation, 9 immune response, 10 metabolism, 11 cell growth, and especially tumorigenesis. 12,13 Moreover, since an increasing number of reports have indicated that their abnormal expression is frequently observed in human cancers, some lncRNAs have been validated as biomarkers for diagnostic, metastasis, recurrence, and poor prognosis, [14][15][16][17] such as MALAT-1 for lung, glioma, gastric, and prostate cancer; [18][19][20][21] HOTAIR for breast, ovarian, pancreatic, and colorectal cancer; [22][23][24][25] and CCAT2 for oral squamous cell carcinoma and bladder cancer. 26,27 Zinc finger antisense 1 (ZFAS1) locus is host to three C/D-box small nucleolar RNAs (snoRNAs), and its transcription initiates from the antisense strand near the 5′ end of the protein-coding gene Znfx1.…”