Welcome to Francis Academic Press

Frontiers in Medical Science Research, 2022, 4(7); doi: 10.25236/FMSR.2022.040703.

Identification of the key miRNAs and target genes in basal cell carcinoma by bioinformatics analysis

Author(s)

Hao Liu1, Lei Tan2, Ling Chen3

Corresponding Author:
Ling Chen
Affiliation(s)

1College of Stomatology, Chongqing Medical University, Chongqing, 400016, China

2College of Nursing, Chongqing Medical University, Chongqing, 400016, China

3The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing, 400016, China

Abstract

The highly tissue-destructive and localized accumulation of basal cell carcinoma(BCC) makes it one of the most important cancers affecting people's lives. Existing therapeutic approaches, including surgical treatment, chemotherapy, and Hedgehog pathway inhibitors, have failed to achieve broad therapeutic effects for various reasons. This study aims to explore additional potential therapeutic targets and possible diagnostic and prognostic biomarkers using bioinformatics analysis. The Gene Expression Omnibus (GEO) database identified the microarray dataset GSE34535. The GEO2R tool was used to screen out differentially expressed genes (DEGs) between BCC and non-lesional skin. Potential target genes of DE-miRNA were screened using the miRWalk, mirDIP and miRTarBase databases. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for target genes were established using the DAVID database. Protein–protein interaction network and miRNA-hub gene network were analyzed based on the STRING database and visualized by Cytoscape software. 51 up-regulated DE-miRNAs and 38 down-regulated DE-miRNAs were identified from the BCC samples. miR-455-5p was mainly up-regulated and miR-139-5p was mainly down-regulated. Two key bub genes MAPK1 and EGFR were identified in the PPI network. Four out of the ten hub genes were regulated by up-regulated miR-18a and four by down-regulated miR-133b. Viral infections were also identified in the study. Bioinformatics identified four miRNAs and two important hub genes that may be associated with BCC, and it was suggested that viruses may play a role in BCC.

Keywords

bioinformatics analysis; basal cell carcinoma; miRNAs

Cite This Paper

Hao Liu, Lei Tan, Ling Chen. Identification of the key miRNAs and target genes in basal cell carcinoma by bioinformatics analysis. Frontiers in Medical Science Research (2022) Vol. 4, Issue 7: 12-21. https://doi.org/10.25236/FMSR.2022.040703.

References

[1] Fania L, Didona D, Morese R, Campana I, Coco V, Di Pietro FR, Ricci F, Pallotta S, Candi E, Abeni D, Dellambra E. (2020) Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches. Biomedicines, 8(11)

[2] Lomas A, Leonardi-Bee J, Bath-Hextall F. (2012) A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol, 166(5), 1069-1080.

[3] Ciążyńska M, Narbutt J, Woźniacka A, Lesiak A. (2018) Trends in basal cell carcinoma incidence rates: a 16-year retrospective study of a population in central Poland. Postepy Dermatol Alergol, 35(1), 47-52.

[4] Dika E, Scarfì F, Ferracin M, Broseghini E, Marcelli E, Bortolani B, Campione E, Riefolo M, Ricci C, Lambertini M. (2020) Basal Cell Carcinoma: A Comprehensive Review. Int J Mol Sci, 21(15).

[5] Dika E, Veronesi G, Patrizi A, De Salvo S, Misciali C, Baraldi C, Mussi M, Fabbri E, Tartari F, Lambertini M. (2020) It's time for Mohs: Micrographic surgery for the treatment of high-risk basal cell  carcinomas of the head and neck regions. Dermatol Ther, 33(4): e13474.

[6] Peris K, Licitra L, Ascierto PA, Corvò R, Simonacci M, Picciotto F, Gualdi G, Pellacani G, Santoro A. (2015) Identifying locally advanced basal cell carcinoma eligible for treatment with vismodegib: an expert panel consensus. Future Oncol, 11(4), 703-712.

[7] Atwood SX, Chang AL, Oro AE. (2012) Hedgehog pathway inhibition and the race against tumor evolution. J Cell Biol, 199(2), 193-197.

[8] Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. (2012) Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med, 366(23), 2171-2179.

[9] Calin GA, Croce CM. (2006) MicroRNA signatures in human cancers. Nat Rev Cancer, 6(11), 857-866.

[10] Sand M, Skrygan M, Sand D, Georgas D, Hahn SA, Gambichler T, Altmeyer P, Bechara FG. (2012) Expression of microRNAs in basal cell carcinoma. Br J Dermatol, 167(4), 847-855.

[11] Heffelfinger C, Ouyang Z, Engberg A, Leffell DJ, Hanlon AM, Gordon PB, Zheng W, Zhao H, Snyder MP, Bale AE. (2012) Correlation of Global MicroRNA Expression with Basal Cell Carcinoma Subtype. G3 (Bethesda), 2(2), 279-286.

[12] Sand M, Bechara FG, Gambichler T, Sand D, Friedländer MR, Bromba M, Schnabel R, Hessam S. (2016) Next-generation sequencing of the basal cell carcinoma miRNome and a description of novel microRNA candidates under neoadjuvant vismodegib therapy: an integrative  molecular and surgical case study. Ann Oncol, 27(2), 332-338.

[13] Yang Q, Hou C, Huang D, Zhuang C, Jiang W, Geng Z, Wang X, Hu L. (2020) miR-455-5p functions as a potential oncogene by targeting galectin-9 in colon cancer. Oncology letters 13(3): 1958-1964, 2017.

[14] Bi H, Shang Z, Jia C, Wu J, Cui B, Wang Q, Ou T. LncRNA RNF144A-AS1 Promotes Bladder Cancer Progression via RNF144A-AS1/miR-455-5p/SOX11 Axis. Onco Targets Ther, 13, 11277-11288.

[15] Zakrzewska K, Regalbuto E, Pierucci F, Arvia R, Mazzoli S, Gori A, de Giorgi V. (2012) Pattern of HPV infection in basal cell carcinoma and in perilesional skin biopsies from immunocompetent patients. Virology journal, 9, 309.

[16] Chen W, Li Q, Zhang G, Wang H, Zhu Z, Chen L. (2020) LncRNA HOXA-AS3 promotes the malignancy of glioblastoma through regulating miR-455-5p/USP3 axis. Journal of cellular and molecular medicine, 24(20), 11755-11767.

[17] Cao J, Wang H, Liu G, Tang R, Ding Y, Xu P, Wang H, Miao J, Gu X, Han S. (2021) LBX2-AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR-455-5p and miR-491-5p sponging. Journal of cellular and molecular medicine, 25(2), 1178-1189.

[18] Wang H, Li ZY, Xu ZH, Chen YL, Lu ZY, Shen DY, Lu JY, Zheng QM, Wang LY, Xu LW, Xue DW, Wu HY, Xia LQ, Li GH. (2020) The prognostic value of miRNA-18a-5p in clear cell renal cell carcinoma and its function via the miRNA-18a-5p/HIF1A/PVT1 pathway. J Cancer, 11(10), 2737-2748.

[19] Kim SY, Kawaguchi T, Yan L, Young J, Qi Q, Takabe K. (2017) Clinical Relevance of microRNA Expressions in Breast Cancer Validated Using the Cancer Genome Atlas (TCGA). Annals of surgical oncology, 24(10), 2943-2949.

[20] Noor MT, Seehra N, Rajput J, Sharma R, Thakur BS. (2020) Evaluation of Roles of MicroRNA-21 and MicroRNA-18a in Esophageal Squamous Cell Carcinoma and Comparison of Their Changes in Expression Post-Chemoradiotherapy. Gastroenterology research, 13(3), 107-113.

[21] Jiao W, Zhang J, Wei Y, Feng J, Ma M, Zhao H, Wang L, Jiao W. (2019) MiR-139-5p regulates VEGFR and downstream signaling pathways to inhibit the  development of esophageal cancer. Dig Liver Dis, 51(1), 149-156.

[22] Jiang Q, Cao Y, Qiu Y, Li C, Liu L, Xu G. (2020) Progression of squamous cell carcinoma is regulated by miR-139-5p/CXCR4. Front Biosci (Landmark Ed), 25, 1732-1745.

[23] Chen J, Yu Y, Chen X, He Y, Hu Q, Li H, Han Q, Ren F, Li J, Li C, Bao J, Ren Z, Duan Z, Cui G, Sun R. (2018) MiR-139-5p is associated with poor prognosis and regulates glycolysis by repressing  PKM2 in gallbladder carcinoma. Cell Prolif, 51(6), e12510.

[24] Zhang HD, Sun DW, Mao L, Zhang J, Jiang LH, Li J, Wu Y, Ji H, Chen W, Wang J, Ma R, Cao HX, Wu JZ, Tang JH. (2015) MiR-139-5p inhibits the biological function of breast cancer cells by targeting Notch1 and mediates chemosensitivity to docetaxel. Biochem Biophys Res Commun, 465(4), 702-713.

[25] Gao G, Tian Z, Zhu HY, Ouyang XY. (2018) miRNA-133b targets FGFR1 and presents multiple tumor suppressor activities in osteosarcoma. Cancer Cell Int, 18, 210.

[26] Rotelli MT, Refolo MG, Lippolis C. (2020) The role of miRNA-133b and its target gene SIRT1 in FAP-derived desmoid tumor. Oncotarget, 11(26), 2484-2492.

[27] Zhou W, Bi X, Gao G, Sun L. (2016) miRNA-133b and miRNA-135a induce apoptosis via the JAK2/STAT3 signaling pathway in human renal carcinoma cells. Biomed Pharmacother, 84, 722-729. 

[28] Liu Z, Li W, Pang Y, Zhou Z, Liu S, Cheng K, Qin Q, Jia Y, Liu S. (2018)SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma. EBioMedicine, 38, 57-68.

[29] Jiang N, Dai Q, Su X, Fu J, Feng X, Peng J. (2020) Role of PI3K/AKT pathway in cancer: the framework of malignant behavior. Molecular biology reports, 47(6), 4587-4629.

[30] Yoon S, Seger R. (2006) The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors, 24(1), 21-44.

[31] Huang FT, Peng JF, Cheng WJ, Zhuang YY, Wang LY, Li CQ, Tang J, Chen WY, Li YH, Zhang SN. (2017) MiR-143 Targeting TAK1 Attenuates Pancreatic Ductal Adenocarcinoma Progression via MAPK and NF-κB Pathway In Vitro. Dig Dis Sci, 62(4), 944-957.

[32] Noguchi S, Yasui Y, Iwasaki J, Kumazaki M, Yamada N, Naito S, Akao Y. (2013) Replacement treatment with microRNA-143 and -145 induces synergistic inhibition of  the growth of human bladder cancer cells by regulating PI3K/Akt and MAPK signaling  pathways. Cancer Lett, 328(2), 353-61.

[33] Chang L, Zhang D, Shi H, Bian Y, Guo R. (2017)MiR-143 inhibits endometrial cancer cell proliferation and metastasis by targeting MAPK1. Oncotarget, 8(48), 84384-84395.

[34] Rajaram P, Chandra P, Ticku S, Pallavi BK, Rudresh KB, Mansabdar P. (2017)Epidermal growth factor receptor: Role in human cancer. Indian J Dent Res, 28(6), 687-694.

[35] Florescu DE, Stepan AE, Mărgăritescu C, Ciurea RN, Stepan MD, Simionescu CE. (2018) The involvement of EGFR, HER2 and HER3 in the basal cell carcinomas aggressiveness. Rom J Morphol Embryol, 59(2), 479-484.

[36] Are C, Rajaram S, Are M, Raj H, Anderson BO, Chaluvarya SR, Vijayakumar M, Song T, Pandey M, Edney JA, Cazap EL. (2013) A review of global cancer burden: trends, challenges, strategies, and a role for surgeons. J Surg Oncol, 107(2), 221-226.

[37] Singh P, Neumann DM. (2020) Persistent HCMV infection of a glioblastoma cell line contributes to the development of resistance to temozolomide. Virus Res, 276, 197829.

[38] Ding D, Han S, Wang Z, Guo Z, Wu A. (2014) Does the existence of HCMV components predict poor prognosis in glioma? J Neurooncol, 116(3), 515-522.

[39] Rechenchoski DZ, Faccin-Galhardi LC, Linhares R, Nozawa C. (2017) Herpesvirus: an underestimated virus. Folia Microbiol (Praha), 62(2), 151-156.

[40] Purushothaman P, Uppal T, Sarkar R, Verma SC. (2016) KSHV-Mediated Angiogenesis in Tumor Progression. Viruses, 8(7), 198.

[41] Schulz TF, Cesarman E. (2015) Kaposi Sarcoma-associated Herpesvirus: mechanisms of oncogenesis. Curr Opin Virol, 14, 116-128.

[42] Tagaya Y, Gallo RC. (2017) The Exceptional Oncogenicity of HTLV-1. Frontiers in microbiology, 8, 1425.