Downregulating microRNA-144 mediates a metabolic shift in lung cancer cells by regulating GLUT1 expression

被引:51
作者
Liu, Min [1 ]
Gao, Jun [1 ]
Huang, Qin [1 ]
Jin, Yanfeng [1 ]
Wei, Zhonghua [1 ]
机构
[1] Shanghai Jiao Tong Univ, Dept Pathol, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China
关键词
RT-PCR; QUANTIFICATION; PROLIFERATION; TARGETS; MIRNAS; GENES;
D O I
10.3892/ol.2016.4468
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Lung cancer is the leading cause of cancer-associated mortality worldwide. Increasing evidence has found that cancer metabolism alternations represent a critical hallmark for lung cancer. There is an urgent requirement to understand and dissect the molecular mechanisms underlying cancer metabolism for lung cancer therapy. It remains largely unknown whether the deregulation of miRNAs contributes to the cancer metabolism. The present study aimed to investigate the role of miR-144 in lung cancer. Glucose uptake rate and lactate production assays demonstrated that miR-144 expression is decreased and therefore enhances the aerobic metabolism in lung cancer cells. In addition, western blot analysis revealed that.miR-1.44 performs this function by increasing the expression of glucose transporter I (GLUTI), leading to an increase in glucose uptake and lactate production. Furthermore, cell viability assays demonstrated that the altered metabolism induced by miR-144 results in the rapid growth of cancer cells. In conclusion, these results identify.rniR-144 as a molecular switch involved in the orchestration of the Warburg effect in lung cancer cells via targeting the expression of GLUT1.
引用
收藏
页码:3772 / 3776
页数:5
相关论文
共 22 条
[1]   Clinical significance of miR-144-ZFX axis in disseminated tumour cells in bone marrow in gastric cancer cases [J].
Akiyoshi, S. ;
Fukagawa, T. ;
Ueo, H. ;
Ishibashi, M. ;
Takahashi, Y. ;
Fabbri, M. ;
Sasako, M. ;
Maehara, Y. ;
Mimori, K. ;
Mori, M. .
BRITISH JOURNAL OF CANCER, 2012, 107 (08) :1345-1353
[2]   MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[3]   The microRNA.org resource: targets and expression [J].
Betel, Doron ;
Wilson, Manda ;
Gabow, Aaron ;
Marks, Debora S. ;
Sander, Chris .
NUCLEIC ACIDS RESEARCH, 2008, 36 :D149-D153
[4]   Real-time quantification of microRNAs by stem-loop RT-PCR [J].
Chen, CF ;
Ridzon, DA ;
Broomer, AJ ;
Zhou, ZH ;
Lee, DH ;
Nguyen, JT ;
Barbisin, M ;
Xu, NL ;
Mahuvakar, VR ;
Andersen, MR ;
Lao, KQ ;
Livak, KJ ;
Guegler, KJ .
NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e179.1-e179.9
[5]   MiR-144 Inhibits Proliferation and Induces Apoptosis and Autophagy in Lung Cancer Cells by Targeting TIGAR [J].
Chen, Shanshan ;
Li, Ping ;
Li, Juan ;
Wang, Yuanyuan ;
Du, Yuwen ;
Chen, Xiaonan ;
Zang, Wenqiao ;
Wang, Huaqi ;
Chu, Heying ;
Zhao, Guoqiang ;
Zhang, Guojun .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2015, 35 (03) :997-1007
[6]   CDKN2A, NF2, and JUN Are Dysregulated Among Other Genes by miRNAs in Malignant Mesothelioma-A miRNA Microarray Analysis [J].
Guled, Mohamed ;
Lahti, Leo ;
Lindholm, Pamela M. ;
Salmenkivi, Kaisa ;
Bagwan, Izhar ;
Nicholson, Andrew G. ;
Knuutila, Sakari .
GENES CHROMOSOMES & CANCER, 2009, 48 (07) :615-623
[7]   Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation [J].
Heiden, Matthew G. Vander ;
Cantley, Lewis C. ;
Thompson, Craig B. .
SCIENCE, 2009, 324 (5930) :1029-1033
[8]   MicroRNA and cancer [J].
Jansson, Martin D. ;
Lund, Anders H. .
MOLECULAR ONCOLOGY, 2012, 6 (06) :590-610
[9]   Differential expression of miR-144* as a novel fecal-based diagnostic marker for colorectal cancer [J].
Kalimutho, Murugan ;
Blanco, Giovanna Del Vecchio ;
Di Cecilia, Serena ;
Sileri, Pierpaolo ;
Cretella, Micaela ;
Pallone, Francesco ;
Federici, Giorgio ;
Bernardini, Sergio .
JOURNAL OF GASTROENTEROLOGY, 2011, 46 (12) :1391-1402
[10]   Tumor cell metabolism: Cancer's Achilles' heel [J].
Kroemer, Guido ;
Pouyssegur, Jacques .
CANCER CELL, 2008, 13 (06) :472-482