<p>Long noncoding RNA LINC01089 predicts clinical prognosis and inhibits cell proliferation and invasion through the Wnt/β-catenin signaling pathway in breast cancer</p>

Abstract

Background: Recently, emerging evidence has indicated crucial roles for long noncoding RNAs (lncRNAs) in breast cancer (BC) development and progression. Our study aimed to investigate the clinical significance of LINC01089 in patients with BC and to determine its biological functions and underlying molecular mechanisms. Materials and methods: Correlations between LINC01089 expression and the clinicopathological characteristics of BC patients were assessed using chi-square tests. The Kaplan-Meier method was used to produce survival curves. The clinical risk characteristics associated with the overall survival and recurrence-free survival of patients with BC were estimated using univariate and multivariate Cox regression analyses. Several methods were used to determine the expression profile, biological functions and underlying mechanisms of LINC01089 in BC, including cell proliferation assays, colony formation assays, flow cytometry, transwell assays, wound healing assays, quantitative real-time polymerase chain reaction and Western blotting. Results: LINC01089 was downregulated in BC tissues and cell lines. Low LINC01089 expression was significantly correlated with age ( P =0.026), lymph node metastasis ( P =0.003), and poor prognosis of patients with BC. According to the multivariate Cox regression analysis results, LINC01089 was an independent prognostic indicator of overall survival ( P =0.032) and recurrence-free survival ( P =0.014). Functional studies revealed significant decreases in the proliferation, migration, and invasion of tumor cells overexpressing LINC01089, and EGF could reverse above effects of LINC01089 on BC cells. Additionally, increased LINC01089 expression promoted apoptosis and cell cycle arrest at G0/G1 phase, accompanied by decreased expression of the key cell cycle regulators CDK4 and CDK6. Loss-of-function assays confirmed partial results. Mechanistically, LINC01089 blocked the Wnt/β-catenin pathway and the expression of downstream target genes by inhibiting β-catenin expression at the transcriptional level. Conclusion: Based on our results, LINC01089 functions as a tumor suppressor and potentially represents a novel prognostic indicator and therapeutic target in BC. Keywords: long noncoding RNA, breast cancer, prognostic indicator, tumor suppressor, the canonical Wnt signaling