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Medical Oncology

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01.05.2019 | Original Paper

In silico identification of key genes and signaling pathways targeted by a panel of signature microRNAs in prostate cancer

verfasst von: Meghna M. Baruah, Neeti Sharma

Erschienen in: Medical Oncology | Ausgabe 5/2019

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Abstract

Accumulating evidence have suggested that some microRNAs are aberrantly expressed in prostate cancer. In our previous work, we had identified a panel of four differentially expressed microRNAs in prostate cancer. In the present study, we have investigated common molecular targets of this panel of miRNAs (DEMs) and key hub genes that can serve as potential candidate biomarkers in the pathogenesis and progression of prostate cancer. A joint bioinformatics approach was employed to identify differentially expressed genes (DEGs) in prostate cancer. Gene enrichment analysis followed by the protein–protein interaction (PPI) network construction and selection of hub genes was further performed using String and Cytoscape, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the identified hub genes was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. In total, 496 genes were identified to be common targets of DEMs in prostate cancer and 13 key hub genes were identified from three modules of the PPI network of the DEGs. Further top five genes viz Rhoa, PI3KCA, CDC42, MAPK3, TP53 were used for Enrichment analysis which revealed their association with vital cellular and functional pathways in prostate cancer indicating their potential as candidate biomarkers in prostate cancer.

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Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.PubMedCrossRef

Velonas V, Woo H, Remedios C, Assinder S. Current status of biomarkers for prostate cancer. Int J Mol Sci. 2013;14(6):11034–60.PubMedPubMedCentralCrossRef

Semjonow A, Brandt B, Oberpenning F, Roth S, Hertle L. Discordance of assay methods creates pitfalls for the interpretation of prostate-specific antigen values. Prostate. 1996;29(S7):3–16.CrossRef

Filella X, Foj L, Augé JM, Molina R, Alcover J. Clinical utility of % p2PSA and prostate health index in the detection of prostate cancer. Clin Chem Lab Med (CCLM). 2014;52(9):1347–55.CrossRef

Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Crowley JJ. Prevalence of prostate cancer among men with a prostate-specific antigen level ≤ 4.0 ng per milliliter. N Eng. J Med. 2004;350(22):2239–46.

Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. BBA Mol Cell Res. 2010;1803(11):1231–43.

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.PubMedCrossRef

Rothschild SI. MicroRNA therapies in cancer. Mol Cell Ther. 2014;2(1):7.PubMedPubMedCentralCrossRef

Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.PubMedPubMedCentralCrossRef

10.

MacFarlane LA, Murphy RP. MicroRNA: biogenesis, function and role in cancer. Curr Genomics. 2010;11(7):537–61.PubMedPubMedCentralCrossRef

11.

Singh AN, Sharma N. In silico Meta-Analysis of Circulatory microRNAs in Prostate Cancer. J Anal Oncol. 2017;6(2):107–16.CrossRef

12.

Kim YK. Extracellular microRNAs as biomarkers in human disease. Chonnam Med J. 2015;51(2):51–7.PubMedPubMedCentralCrossRef

13.

Sita-Lumsden A, Dart DA, Waxman J, Bevan CL. Circulating microRNAs as potential new biomarkers for prostate cancer. Br J Cancer. 2013;108(10):1925.PubMedPubMedCentralCrossRef

14.

Schwarzenbach H, Nishida N, Calin GA, Pantel K. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014;11(3):145.PubMedCrossRef

15.

Sharma N, Baruah MM. The microRNA signatures: aberrantly expressed miRNAs in prostate cancer. Clin Transl Oncol. 2018. https://doi.org/10.1007/s12094-018-1910-8.PubMedCrossRef

16.

Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 2014;43(D1):D146–52.PubMedPubMedCentralCrossRef

17.

Chou CH, Chang NW, Shrestha S, Hsu SD, Lin YL, Lee WH, Tsai TR. miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res. 2015;44(D1):D239–47.PubMedPubMedCentralCrossRef

18.

Sticht C, De La Torre C, Parveen A, Gretz N. miRWalk: an online resource for prediction of microRNA binding sites. PLoS ONE. 2018;13(10):e0206239.PubMedPubMedCentralCrossRef

19.

Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Jensen LJ. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res. 2016;45:D362–8.PubMedPubMedCentralCrossRef

20.

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.PubMedPubMedCentralCrossRef

21.

Bader GD, Hogue CW. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform. 2003;4(1):2.CrossRef

22.

Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8(4):S11.PubMedPubMedCentralCrossRef

23.

Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2008;4(1):44.CrossRef

24.

Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa MKEGG. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 2009;38(suppl_1):D355–60.PubMedPubMedCentralCrossRef

25.

Nogales-Cadenas R, Carmona-Saez P, Vazquez M, Vicente C, Yang X, Tirado F, Pascual-Montano A. GeneCodis: interpreting gene lists through enrichment analysis and integration of diverse biological information. Nucleic Acids Res. 2009;37(suppl_2):W317–22.PubMedPubMedCentralCrossRef

26.

Mi H, Huang X, Muruganujan A, Tang H, Mills C, Kang D, Thomas PD. PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements. Nucleic Acids Res. 2016;45(D1):D183–9.PubMedPubMedCentralCrossRef

27.

Patil N, Gaitonde K. Clinical perspective of prostate cancer. Top Magn Reson Imaging. 2016;25(3):103–8.PubMedCrossRef

28.

Fouad YA, Aanei C. Revisiting the hallmarks of cancer. Am J Cancer Res. 2017;7(5):1016.PubMedPubMedCentral

29.

Gilbert-Ross M, Marcus AI, Zhou W. RhoA, a novel tumor suppressor or oncogene as a therapeutic target. Genes Dis. 2015;2(1):2.PubMedCrossRef

30.

Orgaz JL, Herraiz C, Sanz-Moreno V. Rho GTPases modulate malignant transformation of tumor cells. Small GTPases. 2014;5(4):e29019.PubMedPubMedCentralCrossRef

31.

Hall A. Rho family gtpases. Biochem Soc Trans. 2012;40(6):1378–82.PubMedCrossRef

32.

Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005;21:247–69.PubMedCrossRef

33.

Dopeso H, Rodrigues P, Bilic J, Bazzocco S, Cartón-García F, Macaya I, Martínez-Barriocanal Á. Mechanisms of inactivation of the tumour suppressor gene RHOA in colorectal cancer. Br J Cancer. 2018;118(1):106.PubMedCrossRef

34.

Jeong D, Park S, Kim H, Kim CJ, Ahn TS, Bae SB, Kwon HY. RhoA is associated with invasion and poor prognosis in colorectal cancer. Int J Oncol. 2016;48(2):714–22.PubMedCrossRef

35.

Song L, Guo Y, Xu B. Expressions of Ras Homolog Gene family, member A (RhoA) and cyclooxygenase-2 (COX-2) proteins in early gastric cancer and their role in the development of gastric cancer. Med Sci Monit. 2017;23:2979–84.PubMedPubMedCentralCrossRef

36.

Yoon JH, Choi WS, Kim O, Choi BJ, Nam SW, Lee JY, Park WS. Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression. Gastric Cancer. 2017;20(2):274–85.PubMedCrossRef

37.

Li H, Wang Z, Zhang W, Qian K, Xu W, Zhang S. Fbxw7 regulates tumor apoptosis, growth arrest and the epithelial-to-mesenchymal transition in part through the RhoA signaling pathway in gastric cancer. Cancer Lett. 2016;370(1):39–55.PubMedCrossRef

38.

Liu K, Li X, Wang J, Wang Y, Dong H, Li J. Genetic variants in RhoA and ROCK1 genes are associated with the development, progression and prognosis of prostate cancer. Oncotarget. 2017;8(12):19298.PubMedPubMedCentral

39.

Jason SL, Cui W. Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development. 2016;143(17):3050–60.CrossRef

40.

Moynahan ME, Chen D, He W, Sung P, Samoila A, You D, Baselga J. Correlation between PIK3CA mutations in cell-free DNA and everolimus efficacy in HR+, HER2− advanced breast cancer: results from BOLERO-2. Br J Cancer. 2017;116(6):726–30.PubMedPubMedCentralCrossRef

41.

Bonetti LR, Barresi V, Bettelli S, Caprera C, Manfredini S, Maiorana A. Analysis of KRAS, NRAS, PIK3CA, and BRAF mutational profile in poorly differentiated clusters of KRAS-mutated colon cancer. Hum Pathol. 2017;62:91–8.CrossRef

42.

Green S, Trejo CL, McMahon M. PIK3CA(H1047R) accelerates and enhances KRAS(G12D)-driven lung tumorigenesis. Cancer Res. 2015;75(24):5378–91.PubMedPubMedCentralCrossRef

43.

Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 2002;14(5):381–95.PubMedCrossRef

44.

Zhang S, Cai J, Xie W, Luo H, Yang F. miR 202 suppresses prostate cancer growth and metastasis by targeting PIK3CA. Exp Ther Med. 2018;16(2):1499–504.PubMedPubMedCentral

45.

Pearson HB, Li J, Meniel VS, Fennell CM, Waring P, Montgomery KG, Cullinane C. Identification of Pik3ca mutation as a genetic driver of prostate cancer that cooperates with Pten loss to accelerate progression and castration-resistant growth. Cancer Discov. 2018;8(6):764–79.PubMedCrossRef

46.

Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7(8):606–19.PubMedCrossRef

47.

Kandioler D, Mittlböck M, Kappel S, Puhalla H, Herbst F, Langner C, Hofbauer F. TP53 mutational status and prediction of benefit from adjuvant 5-fluorouracil in stage III colon cancer patients. EBioMedicine. 2015;2(8):825–30.PubMedPubMedCentralCrossRef

48.

Scheel A, Bellile E, McHugh JB, Walline HM, Prince ME, Urba S, Bradford C. Classification of TP53 mutations and HPV predict survival in advanced larynx cancer. Laryngoscope. 2016;126(9):E292–9.PubMedPubMedCentralCrossRef

49.

Gao W, Jin J, Yin J, Land S, Gaither-Davis A, Christie N, Keohavong P. KRAS and TP53 mutations in bronchoscopy samples from former lung cancer patients. Mol Carcinog. 2017;56(2):381–8.PubMedCrossRef

50.

Muller PA, Vousden KH. Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer Cell. 2014;25(3):304–17.PubMedPubMedCentralCrossRef

51.

Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2010;2(1):a001008.PubMedPubMedCentralCrossRef

52.

Humphries-Bickley T, Castillo-Pichardo L, Hernandez-O-Farrill E, Borrero-Garcia LD, Forestier-Roman I, Gerena Y, Vlaar CP. Characterization of a dual Rac/Cdc42 inhibitor MBQ-167 in metastatic cancer. Mol Cancer Ther. 2017;16(5):805–18.PubMedPubMedCentral

53.

Ellenbroek SI, Collard JG. Rho GTPases: functions and association with cancer. Clin Exp Metastasis. 2007;24(8):657–72.PubMedCrossRef

54.

Vega FM, Ridley AJ. Rho GTPases in cancer cell biology. FEBS Lett. 2008;582(14):2093–101.PubMedCrossRef

55.

Ye H, Zhang Y, Geng L, Li Z. Cdc42 expression in cervical cancer and its effects on cervical tumor invasion and migration. Int J Oncol. 2015;46(2):757–63.PubMedCrossRef

56.

Du DS, Yang XZ, Wang Q, Dai WJ, Kuai WX, Liu YL, Tang XJ. Effects of CDC42 on the proliferation and invasion of gastric cancer cells. Mol Med Rep. 2016;13(1):550–4.PubMedCrossRef

57.

Guo J, Yu X, Gu J, Lin Z, Zhao G, Xu F, Ge D. Regulation of CXCR57/AKT-signaling-induced cell invasion and tumor metastasis by RhoA, Rac-1, and Cdc42 in human esophageal cancer. Tumor Biol. 2016;37(5):6371–8.CrossRef

58.

Guo Y, Zhang Z, Wei H, Wang J, Lv J, Zhang K, Wang Q. Cytotoxic necrotizing factor 1 promotes prostate cancer progression through activating the Cdc42–PAK1 axis. J Pathol. 2017;243(2):208–19.PubMedCrossRef

59.

Mahajan NP, Liu Y, Majumder S, Warren MR, Parker CE, Mohler JL, Whang YE. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation. Proc Natl Acad Sci USA. 2007;104(20):8438–43.PubMedCrossRef

60.

Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 2002;12(1):9–18.PubMedCrossRef

61.

Imajo M, Tsuchiya Y, Nishida E. Regulatory mechanisms and functions of MAP kinase signaling pathways. IUBMB Life. 2006;58(5–6):312–7.PubMedCrossRef

62.

Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, Mori M. Epithelial–mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 2010;101(2):293–9.PubMedCrossRef

Titel: In silico identification of key genes and signaling pathways targeted by a panel of signature microRNAs in prostate cancer
verfasst von: Meghna M. Baruah
Neeti Sharma
Publikationsdatum: 01.05.2019
Verlag: Springer US
Erschienen in: Medical Oncology / Ausgabe 5/2019
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-019-1268-y

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In silico identification of key genes and signaling pathways targeted by a panel of signature microRNAs in prostate cancer

Abstract

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