LncRNA AK024094 aggravates the progression of breast cancer through regulating miRNA-181a

T.-Z. Zheng, Y.-T. Li, W.-J. Li

Department of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China. zhengtianzhi@cancerhosp-ln-cmu.com

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• Oncology

OBJECTIVE: The aim of this study was to investigate the role of long noncoding ribonucleic acids (lncRNAs) AK024094 in regulating the progression of breast cancer (BCa) and the potential mechanism. Our findings might help to provide a theoretical basis for the targeted therapy of BCa.

PATIENTS AND METHODS: The relative expression level of lncRNA AK024094 in BCa and adjacent normal tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The prognostic potential of AK024094 in BCa was assessed by the Kaplan-Meier method. Meanwhile, AK024094 level in BCa cell lines was detected by qRT-PCR as well. The regulatory effects of AK024094 on the proliferative, migratory, and invasive abilities of MDA-MB-468 and MCF-7 cells were evaluated by functional assays. The Dual-Luciferase Reporter Gene Assay was applied to verify the binding between AK024094 and miRNA-181a. In addition, the rescue experiments were conducted to uncover the role of AK024094/miRNA-181a in the progression of BCa.

RESULTS: AK024094 was significantly upregulated in BCa tissues and cell lines. Compared with BCa patients with low expression of AK024094, the tumor staging of those with a high level of AK024094 was remarkably worse. Meanwhile, the rate of distant metastasis was significantly higher, and the overall survival was shorter in BCa patients with high expression of AK024094. The knockdown of AK024094 significantly attenuated the proliferative, migratory, and invasive abilities of MDA-MB-468 and MCF-7 cells. Subsequently, miRNA-181a was predicted and verified as the target of AK024094. A negative correlation was identified between the expression levels of AK024094 and miRNA-181a in BCa. Furthermore, the knockdown of miRNA-181a partially reversed the effect of AK024094 on cellular behaviors of BCa cells.

CONCLUSIONS: AK024094 aggravates the malignant progression of BCa, and is closely related to tumor staging, distant metastasis, and poor prognosis of BCa. In addition, AK024094 accelerates the proliferation and metastasis of BCa cells by targeting miRNA-181a.

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