The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer.
The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer.
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miR-34a-LDHA轴调节乳腺癌中的葡萄糖代谢和肿瘤生长
DOI：
10.1038/srep21735
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发表时间：
2016-02-23
影响因子：
4.6
通讯作者：
Xie X
中科院分区：
文献类型：
--
作者：
Xiao X;Huang X;Ye F;Chen B;Song C;Wen J;Zhang Z;Zheng G;Tang H;Xie X
乳酸脱氢酶A （LDHA）与多种癌症有关。本研究的目的是探讨LDHA在乳腺癌中的表达、预后作用和功能。通过实时荧光定量PCR (qRT-PCR)，我们发现LDHA在乳腺癌细胞系和临床标本中均上调。组织微阵列（TMAs）免疫组化（IHC）分析显示，高LDHA表达与细胞增殖、转移和患者总生存期（OS）和无病生存期（DFS）差有关。此外，我们发现LDHA在体外和体内促进糖酵解和细胞增殖。我们还进行了荧光素酶报告基因检测，发现LDHA是miR-34a的直接靶点。miR-34a抑制LDHA可抑制乳腺癌细胞糖酵解和细胞增殖。我们的研究结果为miR-34a通过体外和体内抑制LDHA在乳腺癌中的抑癌作用提供了线索。通过miR-34a靶向LDHA可能是乳腺癌的潜在治疗策略。
Lactate dehydrogenase A (LDHA) is involved in a variety of cancers. The purpose of this study was to investigate the expression, prognostic roles and function of LDHA in breast cancer. We found that LDHA was upregulated in both breast cancer cell lines and clinical specimens using quantitative real-time PCR (qRT-PCR). Immunohistochemistry (IHC) analysis of tissue microarrays (TMAs) showed that high LDHA expression was associated with cell proliferation, metastasis and poor patient overall survival (OS) and disease free survival (DFS). Furthermore, we found that LDHA promoted glycolysis and cell proliferationin vitroandin vivo. We also performed luciferase reporter assays and found that LDHA was a direct target of miR-34a. Repression of LDHA by miR-34a suppressed glycolysis and cell proliferation in breast cancer cellsin vitro. Our findings provide clues regarding the role of miR-34a as a tumor suppressor in breast cancer through the inhibition of LDHA bothin vitroandin vivo. Targeting LDHA through miR-34a could be a potential therapeutic strategy in breast cancer.