4.7 Article

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

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CELL DEATH & DISEASE
卷 9, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41419-018-0582-1

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资金

  1. National Natural Science Foundation of China [81272903, 81672613]
  2. Key Research and Development Program of Shandong Province [2016GGE2775]
  3. Shandong Science and Technology Development Plan [2016CYJS01A02]
  4. Special Support Plan for National High Level Talents (Ten Thousand Talents Program)

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Accumulating evidence indicates that long non-coding RNAs (IncRNAs) play a critical role in cancerous processes as either oncogenes or tumor suppressor genes. Here, we demonstrated that IncRNA-PRLB (progression-associated IncRNA in breast cancer) was upregulated in human breast cancer tissues and breast cancer cell lines. Further evaluation verified that IncRNA-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 IncRNA-PRLB. Both IncRNA-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 IncRNA-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 IncRNA-PRLB overexpression could be partly abrogated by ectopic expression of miR-4766-5p. Taken together, our findings indicated that IncRNA 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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