Journal
CELL DEATH & DISEASE
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41419-018-0582-1
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Funding
- National Natural Science Foundation of China [81272903, 81672613]
- Key Research and Development Program of Shandong Province [2016GGE2775]
- Shandong Science and Technology Development Plan [2016CYJS01A02]
- 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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