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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。

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

机构信息

Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nangang District, Harbin, China.

Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

J Exp Clin Cancer Res. 2017 Nov 13;36(1):158. doi: 10.1186/s13046-017-0630-1.

DOI:10.1186/s13046-017-0630-1
PMID:29132384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5683540/
Abstract

BACKGROUND

MicroRNAs 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 RESULTS

Here 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.

CONCLUSION

Our 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.

摘要

背景

MicroRNAs 在包括乳腺癌(BC)在内的各种人类癌症中作为关键调节剂发挥作用。我们之前的研究已经证明 miR-361-5p 在结直肠癌和胃癌中是一种肿瘤抑制因子。在这项研究中,我们旨在探讨 miR-361-5p 在乳腺癌进展中的作用,并阐述 miR-361-5p 在乳腺癌中发挥作用的机制。

方法和结果

在这里,我们报告 miR-361-5p 在乳腺癌组织中表达下调,与正常乳腺组织相比,并且 miR-361-5p 的表达与 BC 患者的预后呈正相关。功能研究表明,miR-361-5p 的过表达在体内和体外均抑制乳腺癌细胞的增殖、侵袭和转移。机制上,我们发现 miR-361-5p 通过抑制糖酵解来抑制 BC 细胞的增殖。FGFR1,一种糖酵解相关酶的促进剂,被鉴定为 miR-361-5p 的靶标,miR-361-5p 促进糖酵解并抑制氧化磷酸化。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 例 BC 组织的队列中,还发现 miR-361-5p 与 FGFR1 或 MMP-1 之间存在相反的表达模式。

结论

我们的研究结果表明,miR-361-5p 通过分别抑制 FGFR1 和 MMP-1 抑制乳腺癌细胞的糖酵解和侵袭,提示 miR-361-5p 及其靶标可能作为乳腺癌治疗的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/208880c58c11/13046_2017_630_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/4d35bab22dce/13046_2017_630_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/4442b9b8294b/13046_2017_630_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/8fe0bbee486a/13046_2017_630_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/c0caecfcc8b2/13046_2017_630_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/9caf59e83692/13046_2017_630_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/208880c58c11/13046_2017_630_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/4d35bab22dce/13046_2017_630_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/4442b9b8294b/13046_2017_630_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/8fe0bbee486a/13046_2017_630_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/c0caecfcc8b2/13046_2017_630_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/9caf59e83692/13046_2017_630_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc4/5683540/208880c58c11/13046_2017_630_Fig6_HTML.jpg

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