MiR-let-7a Inhibits Cell Proliferation, Migration, and Invasion by Down-regulating PKM2 in Gastric Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Jan 9

PMID 26745603

Citations 54

Authors

Ran Tang

Chao Yang

Xiang Ma

Younan Wang

Dakui Luo

Chi Huang

Zekuan Xu

Ping Liu

Li Yang

Affiliations

Soon will be listed here.

Abstract

In contrast to normal differentiated cells that depend on aerobicoxidation for energy production, cancer cells use aerobic glycolysis as the main source (Warburg's effect). The M2 splice isoform of pyruvate kinase (PKM2) is the key regulator for the aerobic glycolysis, high expression of PKM2 contributes to the aerobic glycolysis, promotes the growth of tumors. In the present study, we found that PKM2 was highly expressed in gastric cancer (GC) tissues and had a strongly inverse correlation with the expression of microRNA-let-7a (miR-let-7a). Furthermore, we found that the overexpression of miR-let-7a markedly suppressed the proliferation, migration, and invasion of GC cells by down-regulating the expression of PKM2. MicroRNAs (miRNAs) are important regulators play key roles in tumorigenesis and tumor progression. Although previous reports showed that let-7 family members act as tumor suppressors in many cancers. The specific regulatory mechanism of miR-let-7a to PKM2 in gastric cancer is still unclear. In this study, we revealed that miR-let-7a function as the antitumor and gene regulatory effects of PKM2 in GC cells.

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References

Noguchi T, Inoue H, Tanaka T . The M1- and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing. J Biol Chem. 1986; 261(29):13807-12. View

Nair V, Maeda L, Ioannidis J . Clinical outcome prediction by microRNAs in human cancer: a systematic review. J Natl Cancer Inst. 2012; 104(7):528-40. PMC: 3317879. DOI: 10.1093/jnci/djs027. View

Warburg O . On the origin of cancer cells. Science. 1956; 123(3191):309-14. DOI: 10.1126/science.123.3191.309. View

Mazurek S, Boschek C, Hugo F, Eigenbrodt E . Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol. 2005; 15(4):300-8. DOI: 10.1016/j.semcancer.2005.04.009. View

Calin G, Croce C . MicroRNA signatures in human cancers. Nat Rev Cancer. 2006; 6(11):857-66. DOI: 10.1038/nrc1997. View

Johnson C, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D . The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007; 67(16):7713-22. DOI: 10.1158/0008-5472.CAN-07-1083. View

Wang L, Yao J, Shi X, Hu L, Li Z, Song T . MicroRNA-302b suppresses cell proliferation by targeting EGFR in human hepatocellular carcinoma SMMC-7721 cells. BMC Cancer. 2013; 13:448. PMC: 3850949. DOI: 10.1186/1471-2407-13-448. View

Taniguchi K, Ito Y, Sugito N, Kumazaki M, Shinohara H, Yamada N . Organ-specific PTB1-associated microRNAs determine expression of pyruvate kinase isoforms. Sci Rep. 2015; 5:8647. PMC: 4342556. DOI: 10.1038/srep08647. View

Reinhart B, Slack F, Basson M, Pasquinelli A, Bettinger J, Rougvie A . The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000; 403(6772):901-6. DOI: 10.1038/35002607. View

10.

Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C . let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007; 131(6):1109-23. DOI: 10.1016/j.cell.2007.10.054. View

11.

Christofk H, Vander Heiden M, Harris M, Ramanathan A, Gerszten R, Wei R . The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008; 452(7184):230-3. DOI: 10.1038/nature06734. View

12.

Esquela-Kerscher A, Trang P, Wiggins J, Patrawala L, Cheng A, Ford L . The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle. 2008; 7(6):759-64. DOI: 10.4161/cc.7.6.5834. View

13.

Gregory P, Bert A, Paterson E, Barry S, Tsykin A, Farshid G . The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008; 10(5):593-601. DOI: 10.1038/ncb1722. View

14.

Kong W, Yang H, He L, Zhao J, Coppola D, Dalton W . MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol. 2008; 28(22):6773-84. PMC: 2573297. DOI: 10.1128/MCB.00941-08. View

15.

Nicoloso M, Spizzo R, Shimizu M, Rossi S, Calin G . MicroRNAs--the micro steering wheel of tumour metastases. Nat Rev Cancer. 2009; 9(4):293-302. DOI: 10.1038/nrc2619. View

16.

Hartgrink H, Jansen E, van Grieken N, van de Velde C . Gastric cancer. Lancet. 2009; 374(9688):477-90. PMC: 4613761. DOI: 10.1016/S0140-6736(09)60617-6. View

17.

Hitosugi T, Kang S, Vander Heiden M, Chung T, Elf S, Lythgoe K . Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal. 2009; 2(97):ra73. PMC: 2812789. DOI: 10.1126/scisignal.2000431. View

18.

David C, Chen M, Assanah M, Canoll P, Manley J . HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature. 2009; 463(7279):364-8. PMC: 2950088. DOI: 10.1038/nature08697. View

19.

He X, Chen J, Zhang Z, Li C, Peng Q, Peng H . The let-7a microRNA protects from growth of lung carcinoma by suppression of k-Ras and c-Myc in nude mice. J Cancer Res Clin Oncol. 2009; 136(7):1023-8. DOI: 10.1007/s00432-009-0747-5. View

20.

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View