Anas Khaleel
ABSTRACT
Colorectal cancer is one of the most common types of cancer in the world, and its incidence is mostly influenced by lifestyle factors. Despite having a much smaller role, genetics also affects the susceptibility and development of colorectal cancer. The aim of the present study is to investigate the regulatory functions of candidate microRNAs (miRs) 1 and 206 in the context of solute carrier family 16 member 3 (SLC16A3) and vascular endothelial growth factor (VEGF) expression. To achieve this, 24 oncogenes targeted by miR-1 and miR-206 were analyzed via GeneMANIA. The miRTarBase database was then employed to ascertain the nature of the miR-oncogene relationship. Our findings illustrate that miR-1/206 indirectly reduce CRC growth and infiltration by targeting the both the SLC16A3 and VEGF genes. Moreover, miR-1/206 targets the VEGF gene to reduce tumor angiogenesis and vasculature. Conclusively, the results of the current study illustrate a novel regulation pathway in CRC cells, suggesting new potential lines of CRC therapy.
- Hughes, L.A.E.; Simons, C.C.J.M.; van den Brandt, P.A.; van Engeland, M.; Weijenberg, M.P. Lifestyle, Diet, and Colorectal Cancer Risk According to (Epi)genetic Instability: Current Evidence and Future Directions of Molecular Pathological Epidemiology. Curr. Colorectal Cancer Rep. 2017, 13, 455--469.Google Scholar
Cross Ref
- Anderson, A.S.; Caswell, S.; Macleod, M.; Craigie, A.M.; Stead, M.; Steele, R.J.C.; Team, T.B. Awareness of Lifestyle and Colorectal Cancer Risk: Findings from the BeWEL Study. Biomed Res. Int. 2015, 2015, 1--5.Google ScholarCross Ref
- Bogaert, J.; Prenen, H. Molecular genetics of colorectal cancer. Ann. Gastroenterol. 2014, 27, 9--14.Google Scholar
- Colussi, D.; Brandi, G.; Bazzoli, F.; Ricciardiello, L.; Colussi, D.; Brandi, G.; Bazzoli, F.; Ricciardiello, L. Molecular Pathways Involved in Colorectal Cancer: Implications for Disease Behavior and Prevention. Int. J. Mol. Sci. 2013, 14, 16365--16385.Google Scholar
- Gonçalves, P.; Martel, F. Regulation of colonic epithelial butyrate transport: Focus on colorectal cancer. Porto Biomed. J. 2016, 1, 83--91.Google ScholarCross Ref
- Kim, H.K.; Lee, I.; Bang, H.; Kim, H.C.; Lee, W.Y.; Yun, S.H.; Lee, J.; Lee, S.J.; Park, Y.S.; Kim, K.-M.; et al. MCT4 Expression Is a Potential Therapeutic Target in Colorectal Cancer with Peritoneal Carcinomatosis. Mol. Cancer Ther. 2018, 17, 838--848.Google Scholar
- Gotanda, Y.; Akagi, Y.; Kawahara, A.; Kinugasa, T.; Yoshida, T.; Ryu, Y.; Shiratsuchi, I.; Kage, M.; Shirouzu, K. Expression of monocarboxylate transporter (MCT)-4 in colorectal cancer and its role: MCT4 contributes to the growth of colorectal cancer with vascular endothelial growth factor. Anticancer Res. 2013, 33, 2941--7.Google Scholar
- Nakayama, Y.; Torigoe, T.; Inoue, Y.; Minagawa, N.; Izumi, H.; Kohno, K.; Yamaguchi, K. Prognostic significance of monocarboxylate transporter 4 expression in patients with colorectal cancer. Exp. Ther. Med. 2012, 3, 25--30.Google ScholarCross Ref
- Johnson, K.E.; Wilgus, T.A. Vascular Endothelial Growth Factor and Angiogenesis in the Regulation of Cutaneous Wound Repair. Adv. wound care 2014, 3, 647--661.Google Scholar
- Bendardaf, R.; Buhmeida, A.; Hilska, M.; Laato, M.; Syrjänen, S.; Syrjänen, K.; Collan, Y.; Pyrhönen, S. VEGF-1 expression in colorectal cancer is associated with disease localization, stage, and long-term disease-specific survival. Anticancer Res. 28, 3865--70.Google Scholar
- George, M.L.; Tutton, M.G.; Janssen, F.; Arnaout, A.; Abulafi, A.M.; Eccles, S.A.; Swift, R.I. VEGF-A, VEGF-C, and VEGF-D in Colorectal Cancer Progression. Neoplasia 2001, 3, 420--427.Google Scholar
- Bartel, D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116, 281--97.Google Scholar
- Masuda, T.; Hayashi, N.; Kuroda, Y.; Ito, S.; Eguchi, H.; Mimori, K. MicroRNAs as Biomarkers in Colorectal Cancer. Cancers (Basel). 2017, 9.Google Scholar
- Schetter, A.J.; Okayama, H.; Harris, C.C. The role of microRNAs in colorectal cancer. Cancer J. 2012, 18, 244--52.Google ScholarCross Ref
- Toiyama, Y.; Takahashi, M.; Hur, K.; Nagasaka, T.; Tanaka, K.; Inoue, Y.; Kusunoki, M.; Boland, C.R.; Goel, A. Serum miR-21 as a Diagnostic and Prognostic Biomarker in Colorectal Cancer. JNCI J. Natl. Cancer Inst. 2013, 105, 849--859.Google ScholarCross Ref
- Chen, X.; Yan, Q.; Li, S.; Zhou, L.; Yang, H.; Yang, Y.; Liu, X.; Wan, X. Expression of the tumor suppressor miR-206 is associated with cellular proliferative inhibition and impairs invasion in ERa-positive endometrioid adenocarcinoma. Cancer Lett. 2012, 314, 41--53.Google ScholarCross Ref
- Zhang, J.; Guo, H.; Zhang, H.; Wang, H.; Qian, G.; Fan, X.; Hoffman, A.R.; Hu, J.-F.; Ge, S. Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene friend leukemia virus integration 1 gene. Cancer 2011, 117, 86--95.Google ScholarCross Ref
- Xu, W.; Zhang, Z.; Zou, K.; Cheng, Y.; Yang, M.; Chen, H.; Wang, H.; Zhao, J.; Chen, P.; He, L.; et al. MiR-1 suppresses tumor cell proliferation in colorectal cancer by inhibition of Smad3-mediated tumor glycolysis. Cell Death Dis. 2017, 8, e2761.Google ScholarCross Ref
- Zhang, W.; Zou, C.; Pan, L.; Xu, Y.; Qi, W.; Ma, G.; Hou, Y.; Jiang, P. MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA. Cell. Physiol. Biochem. 2015, 37, 1123--1133.Google Scholar
- Lewis, B.P.; Burge, C.B.; Bartel, D.P. Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets. Cell 2005, 120, 15--20.Google Scholar
- Krek, A.; Grün, D.; Poy, M.N.; Wolf, R.; Rosenberg, L.; Epstein, E.J.; MacMenamin, P.; da Piedade, I.; Gunsalus, K.C.; Stoffel, M.; et al. Combinatorial microRNA target predictions. Nat. Genet. 2005, 37, 495--500.Google ScholarCross Ref
- Griffiths-Jones, S.; Grocock, R.J.; van Dongen, S.; Bateman, A.; Enright, A.J. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006, 34, D140-D144.Google ScholarCross Ref
- Warde-Farley, D.; Donaldson, S.L.; Comes, O.; Zuberi, K.; Badrawi, R.; Chao, P.; Franz, M.; Grouios, C.; Kazi, F.; Lopes, C.T.; et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010, 38, W214-W220.Google ScholarCross Ref
- Hsu, S.-D.; Tseng, Y.-T.; Shrestha, S.; Lin, Y.-L.; Khaleel, A.; Chou, C.-H.; Chu, C.-F.; Huang, H.-Y.; Lin, C.-M.; Ho, S.-Y.; et al. miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 2014, 42, D78-D85.Google ScholarCross Ref
- Vegran, F.; Boidot, R.; Michiels, C.; Sonveaux, P.; Feron, O. Lactate Influx through the Endothelial Cell Monocarboxylate Transporter MCT1 Supports an NF- B/IL-8 Pathway that Drives Tumor Angiogenesis. Cancer Res. 2011, 71, 2550--2560.Google ScholarCross Ref
- Gallagher, S.M.; Castorino, J.J.; Wang, D.; Philp, N.J. Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231. Cancer Res. 2007, 67, 4182--4189.Google ScholarCross Ref
- Pértega-Gomes, N.; Vizcaíno, J.R.; Miranda-Gonçalves, V.; Pinheiro, C.; Silva, J.; Pereira, H.; Monteiro, P.; Henrique, R.M.; Reis, R.M.; Lopes, C.; et al. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. BMC Cancer 2011, 11, 312.Google Scholar
- Harada, Y.; Ogata, Y.; Shirouzu, K. Expression of vascular endothelial growth factor and its receptor KDR (kinase domain-containing receptor)/Flk-1 (fetal liver kinase-1) as prognostic factors in human colorectal cancer. Int. J. Clin. Oncol. 2001, 6, 221--8.Google ScholarCross Ref
- NOVELLO, C.; PAZZAGLIA, L.; CINGOLANI, C.; CONTI, A.; QUATTRINI, I.; MANARA, M.C.; TOGNON, M.; PICCI, P.; BENASSI, M.S. miRNA expression profile in human osteosarcoma: Role of miR-1 and miR-133b in proliferation and cell cycle control. Int. J. Oncol. 2013, 42, 667--675.Google ScholarCross Ref
- Reid, J.F.; Sokolova, V.; Zoni, E.; Lampis, A.; Pizzamiglio, S.; Bertan, C.; Zanutto, S.; Perrone, F.; Camerini, T.; Gallino, G.; et al. miRNA Profiling in Colorectal Cancer Highlights miR-1 Involvement in MET-Dependent Proliferation. Mol. Cancer Res. 2012, 10, 504--515.Google ScholarCross Ref
- Migliore, C.; Martin, V.; Leoni, V.P.; Restivo, A.; Atzori, L.; Petrelli, A.; Isella, C.; Zorcolo, L.; Sarotto, I.; Casula, G.; et al. MiR-1 Downregulation Cooperates with MACC1 in Promoting MET Overexpression in Human Colon Cancer. Clin. Cancer Res. 2012, 18, 737--747.Google Scholar
- Yan, D.; Dong, X. Da; Chen, X.; Wang, L.; Lu, C.; Wang, J.; Qu, J.; Tu, L. MicroRNA-1/206 Targets c- Met and Inhibits Rhabdomyosarcoma Development. J. Biol. Chem. 2009, 284, 29596--29604.Google ScholarCross Ref
- Yip, L.; Kelly, L.; Shuai, Y.; Armstrong, M.J.; Nikiforov, Y.E.; Carty, S.E.; Nikiforova, M.N. MicroRNA Signature Distinguishes the Degree of Aggressiveness of Papillary Thyroid Carcinoma. Ann. Surg. Oncol. 2011, 18, 2035--2041.Google ScholarCross Ref
- LIU, X.; HE, M.; HOU, Y.; LIANG, B.; ZHAO, L.; MA, S.; YU, Y.; LIU, X. Expression profiles of microRNAs and their target genes in papillary thyroid carcinoma. Oncol. Rep. 2013, 29, 1415--1420.Google ScholarCross Ref
- Parasramka, M.A.; Dashwood, W.M.; Wang, R.; Saeed, H.H.; Williams, D.E.; Ho, E.; Dashwood, R.H. A role for low-abundance miRNAs in colon cancer: the miR-206/Krüppel-like factor 4 (KLF4) axis. Clin. Epigenetics 2012, 4, 16.Google Scholar
Index Terms
- Microrna-1/206 Target both Monocarboxylate Transporter(MCT)-4 and Vascular Endothelial Growth Factor(VEGF)Genes Leading to Inhibition of Tumor Growth
Recommendations
Association of Serum miR-145 with Vascular Endothelial Growth Factor (VEGF) in Patients with Non-Small Cell Lung Cancer
ICBBE '17: Proceedings of the 2017 4th International Conference on Biomedical and Bioinformatics EngineeringNon-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and it is the leading cause of cancer death globally. Vascular endothelial growth factor (VEGF) plays an important role in cancer progression, including lung cancer. ...
Investigating Gene and MicroRNA Expression in Glioblastoma
IJCBS '09: Proceedings of the 2009 International Joint Conference on Bioinformatics, Systems Biology and Intelligent ComputingGlioblastoma is the most common primary brain tumor in adults. Here we present an integrated analysis of microRNA expression and gene expression in 237 tumor tissues and 10 normal tissues. We indentified 1,236 genes, and 131 pathways significantly ...
Computational regulatory network construction from microRNA and transcription factor perspectives
As more genomic and epigenomic data becomes available, it has become possible to construct biological networks from the omics data. Among the biological networks, understanding gene regulatory mechanisms is a very important research problem that can ...
Comments