Prostat Karsinomunda Enerji Metabolizmasının Yeniden Programlanması: İn Siliko Analiz

Yıl 2020, Cilt: 9 Sayı: 4, 350 - 356, 02.01.2021

Mustafa Emre Ercın , Ender Şimşek

https://doi.org/10.37989/gumussagbil.797335

Cited By: 1

Öz

Prostat karsinomunun, dikkate değer bir onkojenik modüle edilmiş metabolik programlama sergileyen, hipoksik ve lipojenik bir solid tümör olduğu bilinmektedir. Glukoz alımının ve Warburg etkisi olarak bilinen aerobik glikolizin artması hipoksik tümörlerin ana metabolik değişiklikleridir. Protein, nükleik asit ve lipid biyosentezi, kanserin metabolik yeniden programlanması ile ilişkili diğer metabolik süreçlerdir. Prostat karsinomunda “Warburg” etkisine ek olarak, alternatif metabolik yolaklarda yağ asitleri, glutamin ve mitokondriyal oksidatif fosforilasyon tümörün progresyonunda önemli katılımcılar olarak kabul edilir. Bu çalışmanın amacı, az diferansiye (seminal vezikül invazyonlu) ve iyi diferansiye prostat karsinomlarında enerji metabolizmasının programlanmasını araştırmaktır. GSE32448 mikrodizi verileri “Gene Expression OmniBus" tan indirildi. Gen ekspresyon seviyesindeki farklılıklar, 40 prostat kanseri örneğinden elde edilen dokuların mRNA transkriptlerinin yeniden analiz edilmesiyle üretildi. R programı kullanılarak biyoenformatik analiz ile "Biobase", "Limma" ve "Geoquery" kütüphaneleri elde edildi. Yağ asidi metabolizması ile ilgili genlerde istatistiksel olarak anlamlı farklılıklar bulunmuştur. Prostat kanserinde lipid metabolizmasının rolüne ilişkin artan farkındalık, bu maligniteye karşı daha iyi tedavi stratejilerinin geliştirilmesine yol açabilir.

Anahtar Kelimeler

Biyoinformatik, Metabolik yeniden programlama, Moleküler Patoloji, Prostat Kanseri

Programming Of Energy Metabolism In Prostate Carcinoma: In Silico Analysis

Öz

Prostate carcinoma is known to be a hypoxic and lipogenic solid tumor, exhibiting a remarkable oncogenic modulated metabolic programming. Increasing intake of glucose and aerobic glycolysis, called the Warburg effect, are main metabolic changes in hypoxic tumors. Protein,nucleid acid , and lipid biosynthesis are the other metabolic processes associated with cancer metabolic rewiring. In addition to “Warburg effect” in prostate carcinoma, fatty acids, glutamine, and mitochondrial oxidative phosphorylation in alternative metabolic pathways are considered main contributors to tumorigenesis. The aim of this study is to investigate reprogramming of energy metabolism in well and poorly differentiated prostate carcinomas with seminal vesical invasion. The GSE32448 gene’s microarray data were downloaded from the "Gene Expression OmniBus". Differences in gene expression levels were generated by re-analyzing the mRNA transcripts of tissues obtained from 40 patients specimens. "Biobase", "Limma" and "Geoquery" libraries were obtained with bioinformatics analysis using R program. Statistically significant differences were found in genes related to fatty acid metabolism. Increased awareness of the role of lipid metabolism in prostate cancer can lead to developing better treatment strategies against this malignancy.

Anahtar Kelimeler

Bioinformatic, Metabolic reprogramming, Molecular pathology, Prostate cancer

Kaynakça

• Darwiche, N. (2020). “Epigenetic mechanisms and the hallmarks of cancer: an intimate affair”. American journal of cancer research, 10 (7), 1954–1978.
• Kreuzaler, P, Panina, Y, Segal, J, Yuneva, M. (2020). “Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion”. Mol Metab, 33,83-101.
• Bhandari, V, Hoey, C, Liu, L et al. (2019). “Molecular landmarks of tumor hypoxia across cancer types”. Nat Genet, 51, 308–318.
• Frezza, C. (2020). “Metabolism and cancer: the future is now”. Br J Cancer, 122 (2),133-135.
• Zheng, J. (2012). “Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation”. Oncology Letters, 4, 1151-1157.
• Phan, L, Yeung, S, Lee, M. (2014). “Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies”. Cancer biology & medicine, 11 (1), 1–19.
• Petan, T, Jarc, E, Jusović, M. (2018). “Lipid Droplets in Cancer: Guardians of Fat in a Stressful World”. Molecules, 23 (8), 1941.
• Ma, Y, Temkin, S, Hawkridge, M, et al. (2018). “Fatty acid oxidation: An emerging facet of metabolic transformation in cancer”. Cancer letters, 435, 92-100.
• Kızılay, F, Çelik, S, Sözen, S. et al. (2020). “Correlation of Prostate-Imaging Reporting and Data Scoring System scoring on multiparametric prostate magnetic resonance imaging with histopathological factors in radical prostatectomy material in Turkish prostate cancer patients: a multicenter study of the Urooncology Association”. Prostate international, 8 (1), 10–15.
• Deep, G, Schlaepfer, IR. (2016). “Aberrant Lipid Metabolism Promotes Prostate Cancer: Role in Cell Survival under Hypoxia and Extracellular Vesicles Biogenesis”. Int J Mol Sci, 17 (7),1061.
• Yamada, M, Takanashi, K, Hamatani, T. et al. (2012). “A medium-chain fatty acid as an alternative energy source in mouse preimplantation development”. Sci Rep 2, 930.
• Golias, T, Kery, M, Radenkovic, S, Papandreou, I. (2019). “Microenvironmental control of glucose metabolism in tumors by regulation of pyruvate dehydrogenase”. Int. J. Cancer, 144, 674-686.
• Wu, X, Daniels, G, Lee, P, Monaco, M. (2014). “Lipid metabolism in prostate cancer”. American journal of clinical and experimental urology, 2 (2), 111–120.
• Huang, F, Wang, K, Shen, J. (2020). “Lipoprotein-associated phospholipase A2: The story continues”. Medicinal research reviews, 40 (1), 79–134.
• Rodriguez, M, Siwko, S, Liu M. (2016). “Prostate-Specific G-Protein Coupled Receptor, an Emerging Biomarker Regulating Inflammation and Prostate Cancer Invasion”. Curr Mol Med,16 (6),526-532.
• Lee, S, Depoortere, I, Hatt, H. (2019). “Therapeutic potential of ectopic olfactory and taste receptors”. Nat Rev Drug Discov, 18, 116–138.
• O'Byrne, SN, Scott, JW, Pilotte, JR, et al. (2020). “In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds”. Molecules, ,25 (2),325.
• Penfold, L, Woods, A, Muckett, P, Nikitin, A, Kent, T, Zhang, S, Graham, R, Pollard, A, Carling, D. (2018). “CAMKK2 Promotes Prostate Cancer Independently of AMPK via Increased Lipogenesis”. Cancer research, 78 (24), 6747–6761.
• Zhao, Z, Zou, S, Guan, X, et al. (2018). “Apolipoprotein E Overexpression Is Associated With Tumor Progression and Poor Survival in Colorectal Cancer”. Front Genet, 9, 650.
• Ren, L, Yi, J, Li, W, et al. (2019). “Apolipoproteins and cancer”. Cancer Med ,8 (16),7032-7043.
• Houten, SM, Denis, S, Argmann, CA, et al. (2012). “Peroxisomal L-bifunctional enzyme (Ehhadh) is essential for the production of medium-chain dicarboxylic acids”. J Lipid Res, 53 (7),1296-1303.
• Rasiah, K, Gardiner-Garden, M, Padilla, E, et al. (2009). “HSD17B4 overexpression, an independent biomarker of poor patient outcome in prostate cancer”. Mol Cell Endocrinol, 301 (1-2),89-96.
• Senga, S, Kawaguchi, K, Kobayashi, N, Ando, A, Fujii, H. (2018). “A novel fatty acid-binding protein 5-estrogen-related receptor α signaling pathway promotes cell growth and energy metabolism in prostate cancer cells”. Oncotarget, 9, 31753-31770.
• Qin, Q, Xu, Y, He, T, et al. (2012). “Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms”. Cell Res, 22, 90–106.
• Gajula, R, Chettiar, S, Williams, R, et al. (2013). “The twist box domain is required for Twist1-induced prostate cancer metastasis”. Molecular cancer research, 11 (11), 1387–1400.
• Hradilkova, K, Maschmeyer, P, Westendorf, K, et al. (2019). “Regulation of Fatty Acid Oxidation by Twist 1 in the Metabolic Adaptation of T Helper Lymphocytes to Chronic Inflammation”. Arthritis Rheumatol, 71 (10),1756-1765.
• Lee, D, Yoo, E, Kim, J, et al. (2020). “NEDD4L downregulates autophagy and cell growth by modulating ULK1 and a glutamine transporter”. Cell Death Dis, 11, 38.
• Lytovchenko, O, Kunji, ERS. (2017). “Expression and putative role of mitochondrial transport proteins in cancer”. Biochim Biophys Acta Bioenerg, 1858 (8), 641-654.
• Zhang, S, Hulver, W, McMillan, R, et al. (2014). “The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility”. Nutr Metab, 11, 10.
• Yang, C, Wang, S, Ruan, H, et al. (2019). “Downregulation of PDK4 Increases Lipogenesis and Associates with Poor Prognosis in Hepatocellular Carcinoma”. J Cancer, 10 (4), 918-926.
• Esteves, P, Pecqueur, C, Alves-Guerra, C. (2014). “UCP2 induces metabolic reprogramming to inhibit proliferation of cancer cells”. Mol Cell Oncol, 2 (1), e975024.