A novel long non-coding RNA-PRLB acts as a tumor promoter through regulating miR-4766-5p/SIRT1 axis in breast cancer

一种新型长链非编码RNA-PRLB通过调控乳腺癌中的miR-4766-5p/SIRT1轴发挥肿瘤启动子作用

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作者:Yiran Liang, Xiaojin Song, Yaming Li, Yuting Sang, Ning Zhang, Hanwen Zhang, Ying Liu, Yi Duan, Bing Chen, Renbo Guo, Wenjing Zhao, Lijuan Wang, Qifeng Yang

Abstract

Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in cancerous processes as either oncogenes or tumor suppressor genes. Here, we demonstrated that lncRNA-PRLB (progression-associated lncRNA in breast cancer) was upregulated in human breast cancer tissues and breast cancer cell lines. Further evaluation verified that lncRNA-PRLB was positively correlated with the extent of metastasis, and its expression was correlated with shorter survival time of breast cancer patients. We identified microRNA miR-4766-5p as an inhibitory target of lncRNA-PRLB. Both lncRNA-PRLB overexpression and miR-4766-5p knockdown could remarkably enhance cell growth, metastasis, and chemoresistance. We also determined that sirtuin 1 (SIRT1) was an inhibitory target of miR-4766-5p, and that SIRT1 was inhibited by both lncRNA-PRLB knockdown and miR-4766-5p overexpression. Significantly, we found that the promotion of cell proliferation and metastasis, the acquisition of chemoresistance, and the increased expression of SIRT1 induced by lncRNA-PRLB overexpression could be partly abrogated by ectopic expression of miR-4766-5p. Taken together, our findings indicated that lncRNA could regulate the progression and chemoresistance of breast cancer via modulating the expression levels of miR-4766-5p and SIRT1, which may have a pivotal role in breast cancer treatment and prognosis prediction.

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