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miR-26a enhances colorectal cancer cell growth by targeting RREB1 deacetylation to activate AKT-mediated glycolysis
Cancer Letters ( IF 9.1 ) Pub Date : 2021-08-19 , DOI: 10.1016/j.canlet.2021.08.017
Bing Chen 1 , Ya-Nan Deng 1 , Xixi Wang 1 , Zijing Xia 2 , Yu He 1 , Peng Zhang 3 , Samina Ejaz Syed 4 , Qiu Li 5 , Shufang Liang 1
Affiliation  

We previously reported the inhibitory effects of microRNA-26a (miR-26a) on the conversion of pyruvate to acetyl coenzyme A in glucose metabolism by directly targeting pyruvate dehydrogenase protein X component in colorectal cancer (CRC) cells (Chen B et al., BMC Cancer 2014). Here, using microRNA in situ hybridization, we confirmed that miR-26a levels were elevated in 77 human CRC tissue samples and further investigated the key miR-26a-mediated metabolic regulation elements and signaling pathways in CRC cells through quantitative proteomic dissection combined with cancer cell biology and biochemical loss-of-function analysis. We found that AKT transcription signaling was a target pathway via miR-26a-mediated deacetylation modification of Ras-responsive element-binding protein 1 (RREB1) at the Lys-60 residue. miR-26a improved the deacetylation level of RREB1, thus contributing to RREB1 binding to the AKT1 promoter to activate AKT transcription and its related signaling pathway in glycolysis. Moreover, miR-26a promoted CRC tumorigenesis in CRC cells and subcutaneous xenograft mice. Thus, miR-26a is a key regulator of CRC tumorigenesis that mediates the deacetylation modification of RREB1 to enhance AKT1 transcription and downstream target gene expression in glycolysis for CRC growth.



中文翻译:


miR-26a 通过靶向 RREB1 去乙酰化激活 AKT 介导的糖酵解来增强结直肠癌细胞生长



我们之前报道了 microRNA-26a (miR-26a) 通过直接靶向结直肠癌 (CRC) 细胞中的丙酮酸脱氢酶蛋白 X 成分,对葡萄糖代谢中丙酮酸转化为乙酰辅酶 A 的抑制作用 (Chen B et al., BMC癌症 2014)。在这里,我们利用microRNA原位杂交证实了77个人类CRC组织样本中miR-26a水平升高,并通过定量蛋白质组学解剖结合癌细胞进一步研究了CRC细胞中miR-26a介导的关键代谢调节元件和信号通路生物学和生化功能丧失分析。我们发现AKT转录信号传导是通过 miR-26a 介导的 Ras 响应元件结合蛋白 1 (RREB1) 在 Lys-60 残基处的脱乙酰化修饰的靶途径。 miR-26a提高了RREB1的去乙酰化水平,从而有助于RREB1与AKT1启动子结合,激活AKT转录及其糖酵解中的相关信号通路。此外,miR-26a 促进 CRC 细胞和皮下异种移植小鼠的 CRC 肿瘤发生。因此,miR-26a 是 CRC 肿瘤发生的关键调节因子,介导 RREB1 的脱乙酰化修饰,以增强AKT1转录和糖酵解中下游靶基因的表达,从而促进 CRC 生长。

更新日期:2021-08-21
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