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c-Myc诱导的长链非编码RNA小核仁RNA宿主基因7调控乳腺癌中的糖酵解

c-Myc-Induced Long Non-Coding RNA Small Nucleolar RNA Host Gene 7 Regulates Glycolysis in Breast Cancer.

作者信息

Zhang Linlei, Fu Yanying, Guo Hao

机构信息

Department of General Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

J Breast Cancer. 2019 Dec;22(4):533-547. doi: 10.4048/jbc.2019.22.e54.

Abstract

PURPOSE

Recent studies have shown that long non-coding RNA (lncRNA) play an important role in cancer metabolism and development. The lncRNA small nucleolar RNA host gene 7 () was reported to be upregulated in colorectal cancer and contribute to its progression. In the current study, we investigated the role of lncRNA- in breast cancer and explored the underlying mechanism.

METHODS

We monitored the expression of lncRNA- in breast cancer tissues and breast cancer cell lines. We evaluated the effects of lncRNA- on cell proliferation and glycolysis in breast cancer cells by knocking down or overexpressing lncRNA-. We searched for the potential microRNA (miRNA) target of lncRNA- and evaluated the effects of the target miRNA on glycolysis. We evaluated the potential regulation of lncRNA- by c-Myc.

RESULTS

LncRNA- was up-regulated in both breast cancer tissues and breast cancer cell lines. Knocking down lncRNA- inhibited breast cancer cell proliferation while overexpressing lncRNA- enhanced cell proliferation. Knocking down lncRNA- resulted in decreased expression of lactate dehydrogenase A (LDHA) and decreased glycolysis. LncRNA- targeted miR-34a-5p to regulate LDHA expression and glycolysis. c-Myc bound to promoter of lncRNA- and positively regulated lncRNA- expression.

CONCLUSION

We demonstrated that c-Myc regulated glycolysis through the lncRNA-/miR-34a-5p/LDHA axis in breast cancer cells.

摘要

目的

近期研究表明,长链非编码RNA(lncRNA)在癌症代谢和发展中发挥重要作用。据报道,lncRNA小核仁RNA宿主基因7()在结直肠癌中上调并促进其进展。在本研究中,我们调查了lncRNA-在乳腺癌中的作用并探索其潜在机制。

方法

我们监测了lncRNA-在乳腺癌组织和乳腺癌细胞系中的表达。通过敲低或过表达lncRNA-,我们评估了lncRNA-对乳腺癌细胞增殖和糖酵解的影响。我们寻找lncRNA-的潜在微小RNA(miRNA)靶点,并评估该靶点miRNA对糖酵解的影响。我们评估了c-Myc对lncRNA-的潜在调控作用。

结果

lncRNA-在乳腺癌组织和乳腺癌细胞系中均上调。敲低lncRNA-抑制乳腺癌细胞增殖,而过表达lncRNA-增强细胞增殖。敲低lncRNA-导致乳酸脱氢酶A(LDHA)表达降低和糖酵解减少。lncRNA-靶向miR-34a-5p以调节LDHA表达和糖酵解。c-Myc与lncRNA-的启动子结合并正向调节lncRNA-的表达。

结论

我们证明了c-Myc在乳腺癌细胞中通过lncRNA-/miR-34a-5p/LDHA轴调节糖酵解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9b3/6933030/efba74a31485/jbc-22-533-g001.jpg

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