Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Roth, M.; Obaidat, A.; Hagenbuch, B. OATPs, OATs and OCTs: The organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br. J. Pharmacol. 2012, 165, 1260–1287. [Google Scholar] [CrossRef] [PubMed]
- Burckhardt, G. Drug transport by Organic Anion Transporters (OATs). Pharmacol. Ther. 2012, 136, 106–130. [Google Scholar] [CrossRef] [PubMed]
- Ciarimboli, G. Organic cation transporters. Xenobiotica 2008, 38, 936–971. [Google Scholar] [CrossRef] [PubMed]
- Li, T.-T.; An, J.-X.; Xu, J.-Y.; Tuo, B.-G. Overview of organic anion transporters and organic anion transporter polypeptides and their roles in the liver. World J. Clin. Cases 2019, 7, 3915–3933. [Google Scholar] [CrossRef]
- Koepsell, H. The SLC22 family with transporters of organic cations, anions and zwitterions. Mol. Asp. Med. 2013, 34, 413–435. [Google Scholar] [CrossRef]
- Pelis, R.M.; Wright, S.H. Chapter Six—SLC22, SLC44, and SLC47 Transporters—Organic Anion and Cation Transporters: Molecular and Cellular Properties. In Current Topics in Membranes; Bevensee, M.O., Ed.; Elsevier Inc. Academic Press: Cambridge, MA, USA, 2014; Volume 73, pp. 233–261. [Google Scholar]
- Dobson, P.D.; Kell, D.B. Carrier-mediated cellular uptake of pharmaceutical drugs: An exception or the rule? Nat. Rev. Drug Discov. 2008, 7, 205–220. [Google Scholar] [CrossRef]
- Sprowl, J.A.; Sparreboom, A. Uptake carriers and oncology drug safety. Drug Metab. Dispos. 2014, 42, 611–622. [Google Scholar] [CrossRef]
- Chin, L.; Hahn, W.C.; Getz, G.; Meyerson, M. Making sense of cancer genomic data. Genes Dev. 2011, 25, 534–555. [Google Scholar] [CrossRef]
- Uhlen, M.; Zhang, C.; Lee, S.; Sjostedt, E.; Fagerberg, L.; Bidkhori, G.; Benfeitas, R.; Arif, M.; Liu, Z.; Edfors, F.; et al. A pathology atlas of the human cancer transcriptome. Science 2017, 357. [Google Scholar] [CrossRef]
- Ashburner, M.; Ball, C.A.; Blake, J.A.; Botstein, D.; Butler, H.; Cherry, J.M.; Davis, A.P.; Dolinski, K.; Dwight, S.S.; Eppig, J.T.; et al. Gene Ontology: Tool for the unification of biology. Nat. Genet. 2000, 25, 25–29. [Google Scholar] [CrossRef]
- Mi, H.; Muruganujan, A.; Ebert, D.; Huang, X.; Thomas, P.D. PANTHER version 14: More genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 2018, 47, D419–D426. [Google Scholar] [CrossRef] [PubMed]
- Tang, Z.; Kang, B.; Li, C.; Chen, T.; Zhang, Z. GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019, 47, W556–W560. [Google Scholar] [CrossRef]
- Goldman, M.; Craft, B.; Hastie, M.; Repečka, K.; McDade, F.; Kamath, A.; Banerjee, A.; Luo, Y.; Rogers, D.; Brooks, A.N.; et al. The UCSC Xena platform for public and private cancer genomics data visualization and interpretation. bioRxiv 2019, 326470. [Google Scholar]
- Liu, J.; Lichtenberg, T.; Hoadley, K.A.; Poisson, L.M.; Lazar, A.J.; Cherniack, A.D.; Kovatich, A.J.; Benz, C.C.; Levine, D.A.; Lee, A.V.; et al. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics. Cell 2018, 173, 400–416.e11. [Google Scholar] [CrossRef] [PubMed]
- Park, J.; Shrestha, R.; Qiu, C.; Kondo, A.; Huang, S.; Werth, M.; Li, M.; Barasch, J.; Susztak, K. Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease. Science 2018, 360, 758–763. [Google Scholar] [CrossRef] [PubMed]
- Koepsell, H. Organic Cation Transporters in Health and Disease. Pharm. Rev. 2020, 72, 253–319. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.; Hong, C.; Chen, E.C.; Yee, S.W.; Xu, L.; Almof, E.U.; Wen, C.; Fujii, K.; Johns, S.J.; Stryke, D.; et al. Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3. Pharm. J. 2013, 13, 110–120. [Google Scholar] [CrossRef]
- Lee, W.K.; Thevenod, F. Oncogenic PITX2 facilitates tumor cell drug resistance by inverse regulation of hOCT3/SLC22A3 and ABC drug transporters in colon and kidney cancers. Cancer Lett. 2019, 449, 237–251. [Google Scholar] [CrossRef]
- Hsu, C.M.; Lin, P.M.; Chang, J.G.; Lin, H.C.; Li, S.H.; Lin, S.F.; Yang, M.Y. Upregulated SLC22A3 has a potential for improving survival of patients with head and neck squamous cell carcinoma receiving cisplatin treatment. Oncotarget 2017, 8, 74348–74358. [Google Scholar] [CrossRef]
- Cervenkova, L.; Vycital, O.; Bruha, J.; Rosendorf, J.; Palek, R.; Liska, V.; Daum, O.; Mohelnikova-Duchonova, B.; Soucek, P. Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma. Sci. Rep. 2019, 9, 19782. [Google Scholar] [CrossRef]
- Lindhurst, M.J.; Fiermonte, G.; Song, S.; Struys, E.; De Leonardis, F.; Schwartzberg, P.L.; Chen, A.; Castegna, A.; Verhoeven, N.; Mathews, C.K.; et al. Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia. Proc. Natl. Acad. Sci. USA 2006, 103, 15927–15932. [Google Scholar] [CrossRef] [PubMed]
- Nies, A.T.; Damme, K.; Kruck, S.; Schaeffeler, E.; Schwab, M. Structure and function of multidrug and toxin extrusion proteins (MATEs) and their relevance to drug therapy and personalized medicine. Arch. Toxicol. 2016, 90, 1555–1584. [Google Scholar] [CrossRef] [PubMed]
- Yonezawa, A.; Masuda, S.; Yokoo, S.; Katsura, T.; Inui, K. Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J. Pharmacol. Exp. Ther. 2006, 319, 879–886. [Google Scholar] [CrossRef] [PubMed]
- Harrach, S.; Schmidt-Lauber, C.; Pap, T.; Pavenstadt, H.; Schlatter, E.; Schmidt, E.; Berdel, W.E.; Schulze, U.; Edemir, B.; Jeromin, S.; et al. MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients. Blood Cancer J. 2016, 6, e470. [Google Scholar] [CrossRef]
- Shen, H.; Lai, Y.; Rodrigues, A.D. Organic Anion Transporter 2: An Enigmatic Human Solute Carrier. Drug Metab. Dispos. 2017, 45, 228–236. [Google Scholar] [CrossRef]
- Hadley, B.; Litfin, T.; Day, C.J.; Haselhorst, T.; Zhou, Y.; Tiralongo, J. Nucleotide Sugar Transporter SLC35 Family Structure and Function. Comput. Struct. Biotechnol. J. 2019, 17, 1123–1134. [Google Scholar] [CrossRef]
- Li, Y.; Wang, S.; Li, T.; Zhu, L.; Ma, C. Tomosyn guides SNARE complex formation in coordination with Munc18 and Munc13. FEBS Lett. 2018, 592, 1161–1172. [Google Scholar] [CrossRef]
- Mon, E.E.; Wei, F.Y.; Ahmad, R.N.R.; Yamamoto, T.; Moroishi, T.; Tomizawa, K. Regulation of mitochondrial iron homeostasis by sideroflexin 2. J. Physiol. Sci. 2019, 69, 359–373. [Google Scholar] [CrossRef] [PubMed]
- Lizak, B.; Szarka, A.; Kim, Y.; Choi, K.S.; Nemeth, C.E.; Marcolongo, P.; Benedetti, A.; Banhegyi, G.; Margittai, E. Glucose Transport and Transporters in the Endomembranes. Int. J. Mol. Sci. 2019, 20, 5898. [Google Scholar] [CrossRef]
- Ancey, P.B.; Contat, C.; Meylan, E. Glucose transporters in cancer - from tumor cells to the tumor microenvironment. FEBS J. 2018, 285, 2926–2943. [Google Scholar] [CrossRef]
- Delanote, V.; Vandekerckhove, J.; Gettemans, J. Plastins: Versatile modulators of actin organization in (patho)physiological cellular processes. Acta Pharmacol. Sin. 2005, 26, 769–779. [Google Scholar] [CrossRef]
- Xin, Z.; Li, D.; Mao, F.; Du, Y.; Wang, X.; Xu, P.; Li, Z.; Qian, J.; Yao, J. PLS3 predicts poor prognosis in pancreatic cancer and promotes cancer cell proliferation via PI3K/AKT signaling. J. Cell. Physiol. 2020. [Google Scholar] [CrossRef] [PubMed]
- Velthaus, A.; Cornils, K.; Hennigs, J.K.; Grub, S.; Stamm, H.; Wicklein, D.; Bokemeyer, C.; Heuser, M.; Windhorst, S.; Fiedler, W.; et al. The Actin Binding Protein Plastin-3 Is Involved in the Pathogenesis of Acute Myeloid Leukemia. Cancers 2019, 11, 1663. [Google Scholar] [CrossRef] [PubMed]
- Kurashige, J.; Yokobori, T.; Mima, K.; Sawada, G.; Takahashi, Y.; Ueo, H.; Takano, Y.; Matsumura, T.; Uchi, R.; Eguchi, H.; et al. Plastin3 is associated with epithelial-mesenchymal transition and poor prognosis in gastric cancer. Oncol. Lett. 2019, 17, 2393–2399. [Google Scholar] [CrossRef]
- Yokobori, T.; Iinuma, H.; Shimamura, T.; Imoto, S.; Sugimachi, K.; Ishii, H.; Iwatsuki, M.; Ota, D.; Ohkuma, M.; Iwaya, T.; et al. Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis. Cancer Res. 2013, 73, 2059–2069. [Google Scholar] [CrossRef] [PubMed]
- Halestrap, A.P. The SLC16 gene family—Structure, role and regulation in health and disease. Mol. Asp. Med. 2013, 34, 337–349. [Google Scholar] [CrossRef] [PubMed]
- Halestrap, A.P.; Wilson, M.C. The monocarboxylate transporter family—Role and regulation. IUBMB Life 2012, 64, 109–119. [Google Scholar] [CrossRef]
- Murray, C.M.; Hutchinson, R.; Bantick, J.R.; Belfield, G.P.; Benjamin, A.D.; Brazma, D.; Bundick, R.V.; Cook, I.D.; Craggs, R.I.; Edwards, S.; et al. Monocarboxylate transporter MCT1 is a target for immunosuppression. Nat. Chem. Biol. 2005, 1, 371–376. [Google Scholar] [CrossRef]
- Parks, S.K.; Chiche, J.; Pouyssegur, J. pH control mechanisms of tumor survival and growth. J. Cell. Physiol. 2011, 226, 299–308. [Google Scholar] [CrossRef]
- Gillies, R.J.; Raghunand, N.; Karczmar, G.S.; Bhujwalla, Z.M. MRI of the tumor microenvironment. J. Magn. Reson. Imaging 2002, 16, 430–450. [Google Scholar] [CrossRef]
- Cardone, R.A.; Casavola, V.; Reshkin, S.J. The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat. Rev. Cancer 2005, 5, 786–795. [Google Scholar] [CrossRef] [PubMed]
- Su, J.; Chen, X.; Kanekura, T. A CD147-targeting siRNA inhibits the proliferation, invasiveness, and VEGF production of human malignant melanoma cells by down-regulating glycolysis. Cancer Lett. 2009, 273, 140–147. [Google Scholar] [CrossRef]
- Gallagher, S.M.; Castorino, J.J.; Philp, N.J. Interaction of monocarboxylate transporter 4 with beta1-integrin and its role in cell migration. Am. J. Physiol. Cell Physiol. 2009, 296, C414–C421. [Google Scholar] [CrossRef] [PubMed]
- Schneiderhan, W.; Scheler, M.; Holzmann, K.H.; Marx, M.; Gschwend, J.E.; Bucholz, M.; Gress, T.M.; Seufferlein, T.; Adler, G.; Oswald, F. CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models. Gut 2009, 58, 1391–1398. [Google Scholar] [CrossRef] [PubMed]
- Gu, J.; Dong, D.; Long, E.; Tang, S.; Feng, S.; Li, T.; Wang, L.; Jiang, X. Upregulated OCT3 has the potential to improve the survival of colorectal cancer patients treated with (m)FOLFOX6 adjuvant chemotherapy. Int. J. Colorectal. Dis. 2019, 34, 2151–2159. [Google Scholar] [CrossRef]
- Farhood, B.; Najafi, M.; Mortezaee, K. CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: A review. J. Cell. Physiol. 2019, 234, 8509–8521. [Google Scholar] [CrossRef]
Tumor Entity | GO Biological Process | Fold Enrichment | Raw p-Value |
---|---|---|---|
Kidney | organic cation transport | 2.57 | 0.02 |
organic anion transport | 1.58 | 0.00007 | |
Lung | organic cation transport | 9.43 | 0.001 |
organic anion transport | 1.06 | 0.8 | |
Endometrial | organic cation transport | 3.39 | 0.03 |
organic anion transport | 1.36 | 0.1 | |
Liver | organic cation transport | 2.65 | 0.3 |
organic anion transport | 3.57 | 0.0000009 |
Tumor Entity | Unfavorable | Favorable |
---|---|---|
Breast Cancer | 0 | 0 |
Cervical Cancer | SLC22A3 | SLC25A42 |
Colorectal Cancer | 0 | 0 |
Endometrial Cancer | SLC25A19 | SAT2, SLC47A1, SLC22A5,MCAT |
Glioma | 0 | 0 |
Head and Neck Cancer | 0 | SLC44A4 |
Liver Cancer | SLC7A8, PSEN1, SLC25A19 | SLC22A1 |
Lung Cancer | SLC44A1 | SAT2,SLC7A8,SLC47A1, SLC25A42 |
Melanoma | 0 | 0 |
Pancreatic Cancer | SLC44A2 | SAT2, SLC22A5, SLC25A45, SLC25A29 |
Prostate cancer | 0 | 0 |
Renal Cancer | LAT2 | PDZK1, RALBP1, SLC22A2, SLC44A2, PSEN1, SLC47A1, SLC44A4, SLC22A5,MCAT,SLC44A1 |
Stomach cancer | 0 | MCAT |
Testis cancer | LAT2 | 0 |
Thyroid cancer | 0 | 0 |
Urothelial Cancer | SLC7A8, SLC22A3 | SLC44A4, SLC25A29 |
Ovarian Cancer | 0 | RALBP1 |
Gene ID | Present in |
---|---|
UNC13B | Renal, Lung, Head and Neck, Pancreatic, Colon |
SFXN2 | Renal, Urothelial, Cervical, Liver |
SIT1 | Head and Neck, Cervical, Endometrial, Melanoma |
MMAA | Renal, Urothelial, Colon |
MPC1 | Renal, Lung, Cervical |
PITPNA | Renal, Endometrial, Pancreatic |
PLA2G2D | Cervical, Breast, Endometrial |
PRAF2 | Lung, Cervical, Pancreatic |
SAT2 | Lung, Endometrial, Pancreatic |
SLC16A11 | Renal, Liver, Pancreatic |
Gene ID | Present in |
---|---|
SLC2A1 | Renal, Urothelial, Lung, Liver, Pancreatic |
PLS3 | Renal, Urothelial, Head and Neck, Pancreatic |
SLC16A1 | Renal, Lung, Endometrial, Pancreatic |
SLC16A3 | Renal, Lung, Cervical, Liver |
LDLR | Kidney, Urothelial, Pancreatic |
SCARB1 | Kidney, Lung, Liver |
SLC15A4 | Kidney, Head and Neck, Liver |
SLC16A2 | Kidney, Urothelial, Breast |
SLC25A32 | Kidney, Lung, Endometrial |
SLC52A2 | Kidney, Cervical, Liver |
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Edemir, B. Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis. Int. J. Mol. Sci. 2020, 21, 4491. https://doi.org/10.3390/ijms21124491
Edemir B. Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis. International Journal of Molecular Sciences. 2020; 21(12):4491. https://doi.org/10.3390/ijms21124491
Chicago/Turabian StyleEdemir, Bayram. 2020. "Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis" International Journal of Molecular Sciences 21, no. 12: 4491. https://doi.org/10.3390/ijms21124491
APA StyleEdemir, B. (2020). Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis. International Journal of Molecular Sciences, 21(12), 4491. https://doi.org/10.3390/ijms21124491