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Long noncoding RNA NBAT-1 suppresses tumorigenesis and predicts favorable prognosis in ovarian cancer.

ABSTRACT: Long noncoding RNA (lncRNA) has been proven to be involved in many biological processes in ovarian cancer (OC). However, the mechanism still remains unknown. In this study, we screened significantly downregulated NBAT-1, which has been proven to play a significant role in breast cancer, clear cell renal cell carcinoma, and neuroblastoma, but not in OC, in two independent datasets with relatively more samples (GSE18520 and GSE38666) from Gene Expression Omnibus. We found that lncRNA NBAT-1 was obviously downregulated in OC tissue compared to normal ovarian tissue (P<0.001) which was free of OC, and the detected levels of NBAT-1 were associated with the International Federation of Gynecology and Obstetrics stage and tumor size guidelines. Moreover, it has been shown that lower levels of NBAT-1 predict poor outcomes of OC. In order to investigate the functional role of NBAT-1, pcDNA-NBAT-1 and empty vector were transfected into TOV112D and OVCAR-3 cell lines. Overexpressed NBAT-1 significantly inhibited cell proliferation, invasion, and migration in both TOV112D and OVCAR-3 cell lines. Finally, Western blot assay indicated that NBAT-1 may exert its function by targeting the ERK1/2 and AKT signaling pathways. In addition, tumor formation growth assay showed that overexpressed NBAT-1 significantly suppresses tumor growth in vivo. In conclusion, our study suggests that NBAT-1 acts as an anti-oncogene in the development of OC.

SUBMITTER: Yan C

PROVIDER: S-EPMC5388203 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Long noncoding RNA NBAT-1 suppresses tumorigenesis and predicts favorable prognosis in ovarian cancer.

Yan Changsheng C Jiang Yi Y Wan Yicong Y Zhang Lin L Liu Jinhui J Zhou Shulin S Cheng Wenjun W

OncoTargets and therapy 20170406

Long noncoding RNA (lncRNA) has been proven to be involved in many biological processes in ovarian cancer (OC). However, the mechanism still remains unknown. In this study, we screened significantly downregulated NBAT-1, which has been proven to play a significant role in breast cancer, clear cell renal cell carcinoma, and neuroblastoma, but not in OC, in two independent datasets with relatively more samples (GSE18520 and GSE38666) from Gene Expression Omnibus. We found that lncRNA NBAT-1 was ob ...[more]

PMID: 28435289

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Project description:Objective:This study aims to investigate the functional role of long noncoding RNA SNHG15 in epithelial ovarian cancer (EOC). Materials and methods:The expression of SNHG15 was measured in EOC cells and tissues using qRT-PCR. The correlation of SNHG15 expression and the clinicopathological characters was statistically analyzed. The prognosis of patients with different clinical features in the high/low SNHG15 expression groups were calculated. Moreover, univariate and multivariate Cox regression analyses were performed to identify the risk factors for poor overall survival (OS) and progression-free survival (PFS). The effect of SNHG15 on the migration and invasion was evaluated using Transwell and Matrigel, respectively. The proliferation ability of EOC cells was tested using colony formation and MTT assay. The influence of SNHG15 on the cisplatin resistance was detected by measuring cell inhibition rate and cell viability. Results:SNHG15 was upegulated in EOC cells and tissues. High SNHG15 expression was correlated with EOC progression and predicted poor OS and PFS in different subgroups of EOC patients. Moreover, multivariate Cox regression analysis defined high SNHG15 expression as an independent risk factor for poor OS and PFS. Furthermore, functional assays showed that the overexpression of SNHG15 promoted migration and invasion, while the loss of SNHG15 suppressed migration and invasion. Furthermore, the proliferation of EOC cells was improved after the ectopic expression of SNHG15, which was suppressed with SNHG15 deficiency. In addition, cisplatin-resistant EOC cells were established for detecting the effect of SNHG15 on EOC chemoresistance. The results showed that cisplatin-resistant EOC cells exhibited much higher levels of SNHG15 expression than controls, and SNHG15 contributed to the chemoresistance of EOC cells. Conclusion:This study confirms that SNHG15 contributes to the migration, invasion, proliferation, and chemoresistance of EOC. SNHG15 may serve as a potential therapeutic target and prognostic biomarker of EOC patients.

Dataset Information

Long noncoding RNA NBAT-1 suppresses tumorigenesis and predicts favorable prognosis in ovarian cancer.

Publications

Long noncoding RNA NBAT-1 suppresses tumorigenesis and predicts favorable prognosis in ovarian cancer.

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