Long noncoding RNA LINC00473 indicates a poor prognosis of breast cancer and accelerates tumor carcinogenesis by competing endogenous sponging miR-497

J. Bai, W.-Y. Zhao, W.-J. Li, Z.-W. Ying, D.-Q. Jiang

Department of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital Institute, Shenyang, Liaoning, China. daqing26@126.com

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• Oncology

OBJECTIVE: Long noncoding RNA LINC00473 (LINC00473) has been reported to be involved in the progression of several tumors. Our present study was conducted to study the potential roles and mechanism of long noncoding RNA LINC00473 (LINC00473) on cells proliferation, migration, invasion, and apoptosis of breast cancer (BC).
PATIENTS AND METHODS: RT-PCR was applied for the analysis of LINC00473 in BC cell lines and tissues samples. The correlations between the LINC00473 levels and clinicopathological parameters were investigated. Kaplan-Meier methods and Cox proportional hazards regression models were explored to reveal potential associations of LINC00473 levels with overall survival of BC patients. The effect of LINC00473 on tumor behavior was evaluated by colony formation, Cell Counting Kit-8, EdU assays, flow-cytometric analysis, wound healing assays and transwell assays. Interactions between LINC00473 and miR-497 were determined using a luciferase reporter assay and RT-PCR assays.
RESULTS: Upregulation of the expression of LINC00473 was found in BC samples and cell lines, in comparison with non-tumor breast tissues and human breast epithelial cells. High expression of LINC00473 was correlated with lymph node metastasis, clinical stage, and poorer outcome in BC patients. Multivariate logistic regression assays further showed LINC00473 as an independent prognostic factor in BC. Lost-of-function assays revealed that knockdown of LINC00473 resulted in the suppression of tumor cell proliferation, promotion of cells apoptosis, inhibition of cells metastasis. Bioinformatics analysis and luciferase reporter assays revealed LINC00473 bonds to miR-497. Further RT-PCR revealed that knockdown of LINC00473 suppressed the expressions of miR-497 in BC cells.
CONCLUSIONS: Our data revealed that LINC00473 acted as a tumor promoter in BC and LINC00473/miR-497 axis may be a novel therapeutic strategy for this tumor.

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