MiR-361-5p inhibits glycolytic metabolism, proliferation and invasion of breast cancer by targeting FGFR1 and MMP-1.

MiR-361-5p inhibits glycolytic metabolism, proliferation and invasion of breast cancer by targeting FGFR1 and MMP-1.
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MiR-361-5p通过靶向FGFR1和MMP-1抑制乳腺癌的糖酵解代谢、增殖和侵袭

DOI:
10.1186/s13046-017-0630-1
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发表时间:
2017-11-13
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Guo B
Guo B
中科院分区:
其他
文献类型:
--
作者:
Ma F;Zhang L;Ma L;Zhang Y;Zhang J;Guo B

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micrornas在包括乳腺癌(BC)在内的多种人类癌症中起着关键的调节作用。我们前期的研究已经证实MiR-361-5p在结直肠癌和胃癌中具有抑瘤作用。在本研究中,我们旨在发现miR-361-5p在乳腺癌进展中的功能,并阐述miR-361-5p在乳腺癌中的作用机制。方法和结果我们报道了miR-361-5p在乳腺癌组织中与正常乳腺组织相比下调,miR-361-5p的表达与BC患者的预后呈正相关。功能研究表明,过表达miR-361-5p在体内和体外均能抑制乳腺癌细胞的增殖、侵袭和转移。在机制上,我们发现miR-361-5p通过抑制糖酵解抑制BC细胞的增殖。FGFR1是糖酵解相关酶的启动子,被认为是miR-361-5p促进糖酵解和抑制氧化磷酸化的靶标。此外,我们证明miR-361-5p通过靶向MMP-1抑制乳腺癌细胞的侵袭和转移。在60个BC组织队列中,miR-361-5p与FGFR1或MMP-1之间也发现了反向表达模式。结论我们的研究结果表明,miR-361-5p分别通过抑制FGFR1和MMP-1抑制乳腺癌细胞的糖酵解和侵袭,提示miR-361-5p及其靶点可能作为乳腺癌治疗的靶点。
BackgroundMicroRNAs function as key regulators in various human cancers, including breast cancer (BC). MiR-361-5p has been proved to be a tumor suppressor in colorectal cancer and gastric cancer in our previous study. In this study, we aim to find out the function of miR-361-5p in breast cancer progression and elaborate the mechanism that miR-361-5p acts its function in breast cancer.Methods and resultsHere we reported that miR-361-5p was down-regulated in breast cancer tissue compared with normal breast tissue and the expression of miR-361-5p was positively associated with prognosis in BC patients. Functional studies showed that overexpression of miR-361-5p suppressed the proliferation, invasion and metastasis of breast cancer cells both in vivo and in vitro. Mechanistically, we found that miR-361-5p inhibited the proliferation of BC cells by suppressing glycolysis. FGFR1, a promoter of glycolysis-related enzyme, was identified as the target of miR-361-5p that promoted glycolysis and repressed oxidative phosphorylation. Furthermore, we demonstrated that miR-361-5p inhibited breast cancer cells invasion and metastasis by targeting MMP-1. An inverse expression pattern was also found between miR-361-5p and FGFR1 or MMP-1 in a cohort of 60 BC tissues.ConclusionOur results indicate that miR-361-5p inhibits breast cancer cells glycolysis and invasion by respectively repressing FGFR1 and MMP-1, suggesting that miR-361-5p and its targets may serve as therapeutic targets in breast cancer treatment.
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发表时间: 1962-01-01
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