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Cancer Lett. 2019 Jan;440-441:211-222. doi: 10.1016/j.canlet.2018.10.025. Epub 2018 Oct 26.

HIF-1α-induced miR-23a∼27a∼24 cluster promotes colorectal cancer progression via reprogramming metabolism.

Author information

1
State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
2
Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute, Nanjing, Jiangsu, 210009, China.
3
Department of General Surgery, Jiangsu Cancer Hospital and Research Institute, Nanjing, Jiangsu, 210009, China.
4
State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China. Electronic address: ybwang@nju.edu.cn.
5
State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China. Electronic address: kzen@nju.edu.cn.
6
State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China. Electronic address: liminli@nju.edu.cn.

Abstract

Tumor cells switch metabolic profile from oxidative phosphorylation to glycolysis in a hypoxic environment for survival and proliferation. The mechanisms governing this metabolic switch, however, remain incompletely understood. Here, we show that three miRNAs in the miR-23a∼27a∼24 cluster, miR-23a, miR-27a and miR-24, are the most upregulated miRNA cluster in colorectal cancer (CRC) under hypoxia. Gain- and loss-of-function assays, a human glucose metabolism array and gene pathway analyses confirm that HIF-1α-induced miR-23a∼27a∼24 cluster collectively regulate glucose metabolic network through regulating various metabolic pathways and targeting multiple tricarboxylic acid cycle (TCA)-related genes. In specific, miR-24/VHL/HIF-1α in CRC form a double-negative feedback loop, which in turn, promotes the cellular transition to the 'high HIF-1α/miR-24 and low VHL' state and facilitates cell survival. Our findings reveal that the miR-23a∼27a∼24 cluster is critical regulator switching CRC metabolism from oxidative phosphorylation to glycolysis, and controlling their expression can suppress colorectal cancer progression.

KEYWORDS:

Feedback; Metabolism reprogramming; miRNA

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