PDL1 And LDHA act as ceRNAs in triple negative breast cancer by regulating miR-34a.
PDL1 And LDHA act as ceRNAs in triple negative breast cancer by regulating miR-34a.
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PDL1 和 LDHA 通过调节 miR-34a 在三阴性乳腺癌中充当 ceRNA
DOI：
10.1186/s13046-017-0593-2
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发表时间：
2017-09-15
期刊：
影响因子：
--
通讯作者：
Xie X
中科院分区：
文献类型：
--
作者：
Huang X;Xie X;Wang H;Xiao X;Yang L;Tian Z;Guo X;Zhang L;Tang H;Xie X
本研究旨在阐明程序性死亡配体1（programmed death ligand 1，PDL 1）、乳酸脱氢酶A（lactate dehydrogenase A，LDHA）和miR-34 a在三阴性乳腺癌（triple negative breast cancer，TNBC）中的调控作用，探讨PDL 1和LDHA作为竞争性内源性RNA（competitive endogenous RNAs，ceRNAs）通过调控miR-34 a在TNBC中的作用和机制。采用定量RT-PCR（qRT-PCR）和免疫组化（IHC）方法检测PDL 1、LDHA和miR-34 a在TNBC中的表达及其相关性。通过MTS细胞存活率、Transwell迁移率、葡萄糖消耗和乳酸产生测定以及流式细胞术，并构建小鼠异种移植模型，探讨PDL 1 3 'UTR和LDHA 3' UTR以及miR-34 a在TNBC中的功能和调控。PDL 1和LDHA的共表达与TNBC的不良结局相关。PDL 1和LDHA都是miR-34 a的靶标，并且PDL 1和LDHA的3 'UTR都具有miR-34 a的结合位点。miR-34 a可抑制PDL 1和LDHA的功能。结论PDL 1和LDHA在TNBC中通过调控miR-34 a的表达，发挥各自的作用，为TNBC的治疗提供新的理论依据。同时靶向PDL 1和LDHA，将联合收割机免疫治疗和代谢靶向治疗相结合，可能会为乳腺癌，特别是TNBC的治疗带来一些启示。
BackgroudThe purpose of this study was to elucidate the regulation of programmed death ligand 1 (PDL1), lactate dehydrogenase A (LDHA) and miR-34a in triple negative breast cancer (TNBC) and to explore the function and mechanism of PDL1 and LDHA as competitive endogenous RNAs (ceRNAs) in TNBC via regulation of miR-34a.MethodsWestern blotting, quantitative RT-PCR (qRT-PCR) and immunohistochemistry (IHC) assays were conducted to explore the expression of PDL1, LDHA and miR-34a in TNBC and correlations between them. MTS cell viability, Transwell migration, glucose consumption and lactate production assays and flow cytometry were performed and mouse xenograft models were constructed to explore the functions and regulation of the PDL1 3’UTR and LDHA 3’UTR and miR-34a in TNBC.ResultsWe found that PDL1 and LDHA were synchronously upregulated in TNBC cell lines and tissues. Co-expression of PDL1 and LDHA was correlated with poor outcome in TNBC. Both PDL1 and LDHA are targets of miR-34a, and the 3’UTRs of PDL1 and LDHA both have binding sites for miR-34a. The functions of PDL1 and LDHA were inhibited by miR-34a. In addition, PDL1 and LDHA acted as ceRNAs to promote the expression and function of each other through regulation of miR-34a in TNBC.ConclusionsThis study provides a new theoretical basis for a novel TNBC therapeutic strategy. Simultaneously targeting PDL1 and LDHA, which would combine immunotherapy and metabolically targeted treatments, might shed some light on the treatment of breast cancer, especially TNBC.
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