miR-214 modulates cisplatin sensitivity of osteosarcoma cells through regulation of anaerobic glycolysis

Y-D. Song; D-D. Li; Y. Guan; Y-L. Wang; J. Zheng

doi:10.14715/cmb/2017.63.9.14

Issue

Vol. 63 No. 9: Issue 9

Issue Published : September 30, 2017

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miR-214 modulates cisplatin sensitivity of osteosarcoma cells through regulation of anaerobic glycolysis

https://doi.org/10.14715/cmb/2017.63.9.14

Y-D. Song

Department of Orthopedics, General Hospital of Daqing Oil Field, Heilongjiang 163001, China

D-D. Li

General Hospital of Daqing Oil Field, Heilongjiang 163001, China

Y. Guan

Department of Orthopedics, First Affiliated Hospital of Harbin Medical University, Harbin 150080, Heilongjiang, China

Y-L. Wang

General Hospital of Daqing Oil Field, Heilongjiang 163001, China

J. Zheng

Shenzhen Hospital of Southern Medical University, Shenzhen 518110, China

Corresponding Author(s) : J. Zheng

jie_zheng5@163.com

Cellular and Molecular Biology, Vol. 63 No. 9: Issue 9
Article Published : September 30, 2017

Abstract

Osteosarcoma is the most frequent primary bone tumor originating from adolescents and young adults. Despite improvements in the chemo- or radio- therapy of osteosarcoma patients, survival rate has not increased and drug resistance becomes a major factor that limits the effectiveness. Therefore, investigation of new treatment modalities is urgently required to optimize therapeutic options. Our previous study described an oncogenic role of miR-214 through promotion of osteosarcoma cells proliferation. In this study, we report miR-214 contributes to cisplatin resistance in osteosarcoma cells. Overexpression of miR-214 decreased the cisplatin sensitivity. By establishing an osteosarcoma cisplatin resistant cell line, we find miR-214 is significantly upregulated in cisplatin resistant cells. Moreover, we show miR-214 promotes anaerobic glycolysis rates of osteosarcoma cells but suppresses mitochondrial oxidative phosphorylation. Consistently, cisplatin resistant cells exhibit upregulated glycolysis but decreased mitochondrial oxidative phosphorylation, a phenotype called "Warburg effect”. Finally, we demonstrate inhibition of glycolysis by either glycolysis inhibitor or miR-214 inhibition significantly re-sensitizes cisplatin resistant osteosarcoma cells. In summary, this study illustrates a miRNA-involved chemosensitivity of osteosarcoma and will contribute to the developments of therapeutic agents for the anti-chemoresistance treatments.

Keywords

miR-214 Osteosarcoma cells Anaerobic glycolysis.

Song, Y.-D., Li, D.-D., Guan, Y., Wang, Y.-L., & Zheng, J. (2017). miR-214 modulates cisplatin sensitivity of osteosarcoma cells through regulation of anaerobic glycolysis. Cellular and Molecular Biology, 63(9), 75–79. https://doi.org/10.14715/cmb/2017.63.9.14

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References

References
Kansara M, Teng MW, Smyth MJ, Thomas DM. Translational biology of osteosarcoma. Nat Rev Cancer 2014; 14:722-735.
Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol 2013; 25:398-406.
O'Kane G, Cadoo KA, Walsh EM, Emerson R, Dervan P, O'Keane C, et al. Perioperative chemotherapy in the treatment of osteosarcoma: A 26-year single institution review. Clin Sarcoma Res 2015; 5:17.
Dasari S, Tchounwou PB. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol 2014; 740:364-378.
Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bellan A, et al. Systems biology of cisplatin resistance: Past, present and future. Cell Death Dis 2014; 5:e1257.
Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 2013; 12:847-865.
Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014; 15:509-524.
Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 2015; 15:321-333.
Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol Med 2014; 20:460-469.
Xu Z, Wang T. MiR-214 promotes the proliferation and invasion of osteosarcoma cells through direct suppression of LZTS1. Biochem Biophys Res Commun 2014; 449:190-195.
Liu CJ, Yu KL, Liu GL, Tian DH. MiR"‘214 promotes osteosarcoma tumor growth and metastasis by decreasing the expression of PTEN. Mol Med Rep 2015; 12:6261-6266.
Barr MP, Gray SG, Hoffmann AC, Hilger RA, Thomale J, O'Flaherty JD, et al. Generation and characterisation of cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature. PLoS One 2013; 8:e54193.
Pelicano H, Martin DS, Xu RH, Huang P. Glycolysis inhibition for anticancer treatment. Oncogene 2006; 25:4633-4646.
Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang JW, et al. MicroRNA expression profiling in human ovarian cancer: MiR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 2008; 68:425-433.
Wang F, Liu M, Li X, Tang H. MiR-214 reduces cell survival and enhances cisplatin-induced cytotoxicity via down-regulation of Bcl2l2 in cervical cancer cells. FEBS Lett 2013; 587:488-495.
Phatak P, Byrnes KA, Mansour D, Liu L, Cao S, Li R, et al. Overexpression of miR-214-3p in esophageal squamous cancer cells enhances sensitivity to cisplatin by targeting survivin directly and indirectly through CUG-BP1. Oncogene 2016; 35:2087-2097.
Martinez-Outschoorn UE, Peiris-Pagés M, Pestell RG, Sotgia F, Lisanti MP. Cancer metabolism: A therapeutic perspective. Nat Rev Clin Oncol 2017; 14:11-31.
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 2009; 324:1029-1033.
Rahman M, Hasan MR. Cancer metabolism and drug resistance. Metabolites 2015; 5:571-600.

References

Kansara M, Teng MW, Smyth MJ, Thomas DM. Translational biology of osteosarcoma. Nat Rev Cancer 2014; 14:722-735.

Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol 2013; 25:398-406.

O'Kane G, Cadoo KA, Walsh EM, Emerson R, Dervan P, O'Keane C, et al. Perioperative chemotherapy in the treatment of osteosarcoma: A 26-year single institution review. Clin Sarcoma Res 2015; 5:17.

Dasari S, Tchounwou PB. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol 2014; 740:364-378.

Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bellan A, et al. Systems biology of cisplatin resistance: Past, present and future. Cell Death Dis 2014; 5:e1257.

Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 2013; 12:847-865.

Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014; 15:509-524.

Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 2015; 15:321-333.

Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol Med 2014; 20:460-469.

Xu Z, Wang T. MiR-214 promotes the proliferation and invasion of osteosarcoma cells through direct suppression of LZTS1. Biochem Biophys Res Commun 2014; 449:190-195.

Liu CJ, Yu KL, Liu GL, Tian DH. MiR"‘214 promotes osteosarcoma tumor growth and metastasis by decreasing the expression of PTEN. Mol Med Rep 2015; 12:6261-6266.

Barr MP, Gray SG, Hoffmann AC, Hilger RA, Thomale J, O'Flaherty JD, et al. Generation and characterisation of cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature. PLoS One 2013; 8:e54193.

Pelicano H, Martin DS, Xu RH, Huang P. Glycolysis inhibition for anticancer treatment. Oncogene 2006; 25:4633-4646.

Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang JW, et al. MicroRNA expression profiling in human ovarian cancer: MiR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 2008; 68:425-433.

Wang F, Liu M, Li X, Tang H. MiR-214 reduces cell survival and enhances cisplatin-induced cytotoxicity via down-regulation of Bcl2l2 in cervical cancer cells. FEBS Lett 2013; 587:488-495.

Phatak P, Byrnes KA, Mansour D, Liu L, Cao S, Li R, et al. Overexpression of miR-214-3p in esophageal squamous cancer cells enhances sensitivity to cisplatin by targeting survivin directly and indirectly through CUG-BP1. Oncogene 2016; 35:2087-2097.

Martinez-Outschoorn UE, Peiris-Pagés M, Pestell RG, Sotgia F, Lisanti MP. Cancer metabolism: A therapeutic perspective. Nat Rev Clin Oncol 2017; 14:11-31.

Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 2009; 324:1029-1033.

Rahman M, Hasan MR. Cancer metabolism and drug resistance. Metabolites 2015; 5:571-600.

Author biographies is not available.