Bioinformatics analysis of the microRNA-mRNA network in sebaceous gland carcinoma of the eyelid

Hirano,Tetsushi; Yunoki,Tatsuya; Furusawa,Yukihiro; Tabuchi,Yoshiaki; Hayashi,Atsushi

doi:10.3892/mmr.2020.11682

Bioinformatics analysis of the microRNA-mRNA network in sebaceous gland carcinoma of the eyelid

Authors:
- Tetsushi Hirano
- Tatsuya Yunoki
- Yukihiro Furusawa
- Yoshiaki Tabuchi
- Atsushi Hayashi
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Affiliations: Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama 930-0194, Japan, Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan, Department of Liberal Arts and Sciences, Toyama Prefectural University, Toyama 939-0398, Japan
Published online on: November 10, 2020 https://doi.org/10.3892/mmr.2020.11682
Article Number: 44
Copyright: © Hirano et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sebaceous gland carcinoma (SGC) of the eyelid is an uncommon aggressive tumor with a relatively high rate of local recurrence and a poor prognosis following metastasis. However, the molecular mechanisms underlying the pathogenesis of SGC remain unclear. The purpose of the present study was to clarify microRNA (miRNA) expression profiles in SGC and to explore novel miRNA‑mRNA networks of SGC. A small RNA‑sequencing analysis was performed to identify miRNAs differentially expressed between SGC and sebaceous adenoma control samples. Bioinformatics analyses were conducted to reveal biological functions, canonical pathways and molecular interaction networks using integrated miRNA‑mRNA datasets, including mRNA expression profiles of SGC from our previous study. The present results demonstrated that 16 upregulated miRNAs and 516 downregulated mRNAs were associated with loss of lipid metabolism function and enriched in cholesterol biosynthesis pathways. By contrast, 29 downregulated miRNAs and 194 upregulated mRNAs were mainly associated with the promotion of cell survival and proliferation in addition to enrichment of DNA damage‑induced cell cycle‑regulation pathways. Furthermore, network analyses revealed that the upregulated miRNAs, miR‑130a‑3p and miR‑939‑5p, and the downregulated miRNAs, miR‑146a‑5p, miR‑149‑3p, miR‑193a‑3p, miR‑195‑5p and miR‑4671‑3p, could be upstream regulators related to these functional changes of SGC. These results improved the understanding of molecular mechanisms of SGC and may help to improve the diagnosis of SGC.

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1	Shields JA, Demirci H, Marr BP, Eagle RC Jr and Shields CL: Sebaceous carcinoma of the ocular region: A review. Surv Ophthalmol. 50:103–122. 2005. View Article : Google Scholar : PubMed/NCBI
2	Cook BE Jr and Bartley GB: Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmsted County, Minnesota. Ophthalmology. 106:746–750. 1999. View Article : Google Scholar : PubMed/NCBI
3	Takamura H and Yamashita H: Clinicopathological analysis of malignant eyelid tumor cases at Yamagata university hospital: Statistical comparison of tumor incidence in Japan and in other countries. Jpn J Ophthalmol. 49:349–354. 2005. View Article : Google Scholar : PubMed/NCBI
4	Buitrago W and Joseph AK: Sebaceous carcinoma: the great masquerader: emgerging concepts in diagnosis and treatment. Dermatol Ther. 21:459–466. 2008. View Article : Google Scholar : PubMed/NCBI
5	Lai TF, Huilgol SC, Selva D and James CL: Eyelid sebaceous carcinoma masquerading as in situ squamous cell carcinoma. Dermatol Surg. 30:222–225. 2004. View Article : Google Scholar : PubMed/NCBI
6	Kan LW, Leu YS, Tzen CY and Wu CH: Recurrent sebaceous gland carcinoma of eyelid previously diagnosed as basal cell carcinoma: Case report. Am J Otolaryngol. 32:620–623. 2011. View Article : Google Scholar : PubMed/NCBI
7	Jakobiec FA and Mendoza PR: Eyelid sebaceous carcinoma: Clinicopathologic and multiparametric immunohistochemical analysis that includes adipophilin. Am J Ophthalmol. 157:186–208.e2. 2014. View Article : Google Scholar : PubMed/NCBI
8	Milman T, Schear MJ and Eagle RC Jr: Diagnostic utility of adipophilin immunostain in periocular carcinomas. Ophthalmology. 121:964–971. 2014. View Article : Google Scholar : PubMed/NCBI
9	Mulay K, White VA, Shah SJ and Honavar SG: Sebaceous carcinoma: Clinicopathologic features and diagnostic role of immunohistochemistry (including androgen receptor). Can J Ophthalmol. 49:326–332. 2014. View Article : Google Scholar : PubMed/NCBI
10	Yunoki T, Miyakoshi A, Otsuka M and Hayashi A: Clinicopathological features of considerable reduction in androgen receptor expression in sebaceous gland carcinoma of the eyelid. Int Ophthalmol. 39:1703–1708. 2019. View Article : Google Scholar : PubMed/NCBI
11	Shields JA, Demirci H, Marr BP, Eagle RC Jr and Shields CL: Sebaceous carcinoma of the eyelids: Personal experience with 60 cases. Ophthalmology. 111:2151–2157. 2004. View Article : Google Scholar : PubMed/NCBI
12	Zürcher M, Hintschich CR, Garner A, Bunce C and Collin JR: Sebaceous carcinoma of the eyelid: A clinicopathological study. Br J Ophthalmol. 82:1049–1055. 1998. View Article : Google Scholar : PubMed/NCBI
13	Muqit MM, Roberts F, Lee WR and Kemp E: Improved survival rates in sebaceous carcinoma of the eyelid. Eye (Lond). 18:49–53. 2004. View Article : Google Scholar : PubMed/NCBI
14	Song A, Carter KD, Syed NA, Song J and Nerad JA: Sebaceous cell carcinoma of the ocular adnexa: Clinical presentations, histopathology, and outcomes. Ophthal Plast Reconstr Surg. 24:194–200. 2008. View Article : Google Scholar : PubMed/NCBI
15	Kiyosaki K, Nakada C, Hijiya N, Tsukamoto Y, Matsuura K, Nakatsuka K, Daa T, Yokoyama S, Imaizumi M and Moriyama M: Analysis of p53 mutations and the expression of p53 and p21WAF1/CIP1 protein in 15 cases of sebaceous carcinoma of the eyelid. Invest Ophthalmol Vis Sci. 51:7–11. 2010. View Article : Google Scholar : PubMed/NCBI
16	Jayaraj P, Sen S, Dhanaraj PS, Jhajhria R, Singh S and Singh VK: Immunohistochemical expression of X-linked inhibitor of apoptosis in eyelid sebaceous gland carcinoma predicts a worse prognosis. Indian J Ophthalmol. 65:1109–1113. 2017. View Article : Google Scholar : PubMed/NCBI
17	Yunoki T, Tabuchi Y and Hayashi A: Expression of anti-apoptotic protein BAG3 in human sebaceous gland carcinoma of the eyelid. Anticancer Res. 37:1931–1934. 2017. View Article : Google Scholar : PubMed/NCBI
18	Erovic BM, Al Habeeb A, Harris L, Goldstein DP, Kim D, Ghazarian D and Irish JC: Identification of novel target proteins in sebaceous gland carcinoma. Head Neck. 35:642–648. 2013. View Article : Google Scholar : PubMed/NCBI
19	Bhardwaj M, Sen S, Sharma A, Kashyap S, Chosdol K, Pushker N, Bajaj MS and Bakhshi S: ZEB2/SIP1 as novel prognostic indicator in eyelid sebaceous gland carcinoma. Hum Pathol. 46:1437–1442. 2015. View Article : Google Scholar : PubMed/NCBI
20	Lee MJ, Kim N, Choung HK, Choe JY, Khwarg SI and Kim JE: Increased gene copy number of HER2 and concordant protein overexpression found in a subset of eyelid sebaceous gland carcinoma indicate HER2 as a potential therapeutic target. J Cancer Res Clin Oncol. 142:125–133. 2016. View Article : Google Scholar : PubMed/NCBI
21	Kim N, Choung HK, Lee MJ, Khwarg SI and Kim JE: Cancer stem cell markers in eyelid sebaceous gland carcinoma: High expression of ALDH1, CD133, and ABCG2 correlates with poor prognosis. Invest Ophthalmol Vis Sci. 56:1813–1819. 2015. View Article : Google Scholar : PubMed/NCBI
22	Yunoki T, Hirano T, Tabuchi Y, Furusawa Y, Torigoe M, Nakajima T, Imura J and Hayashi A: CDKN2A, CDK1, and CCNE1 overexpression in sebaceous gland carcinoma of eyelid. Int Ophthalmol. 40:343–350. 2020. View Article : Google Scholar : PubMed/NCBI
23	Olive V, Minella AC and He L: Outside the coding genome, mammalian microRNAs confer structural and functional complexity. Sci Signal. 8:re22015. View Article : Google Scholar : PubMed/NCBI
24	Kent OA and Mendell JT: A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene. 25:6188–6196. 2006. View Article : Google Scholar : PubMed/NCBI
25	Zhang B, Pan X, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar : PubMed/NCBI
26	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
27	Hayes J, Peruzzi PP and Lawler S: MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol Med. 20:460–469. 2014. View Article : Google Scholar : PubMed/NCBI
28	Bhardwaj M, Sen S, Chosdol K, Sharma A, Pushker N, Kashyap S, Bakhshi S and Bajaj MS: miRNA-200c and miRNA-141 as potential prognostic biomarkers and regulators of epithelial-mesenchymal transition in eyelid sebaceous gland carcinoma. Br J Ophthalmol. 101:536–542. 2017. View Article : Google Scholar : PubMed/NCBI
29	Bladen JC, Wang J, Sangaralingam A, Moosajee M, Fitchett C, Chelala C, Beaconsfield M, O'Toole EA, Philpott MP and Ezra DG: MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma. Sci Rep. 8:75312018. View Article : Google Scholar : PubMed/NCBI
30	Tetzlaff MT, Curry JL, Yin V, Pattanaprichakul P, Manonukul J, Uiprasertkul M, Manyam GC, Wani KM, Aldape K, Zhang L, et al: Distinct pathways in the pathogenesis of sebaceous carcinomas implicated by differentially expressed microRNAs. JAMA Ophthalmol. 133:1109–1116. 2015. View Article : Google Scholar : PubMed/NCBI
31	Furusawa Y, Yunoki T, Hirano T, Minagawa S, Izumi H, Mori H, Hayashi A and Tabuchi Y: Identification of genes and genetic networks associated with BAG3 dependent cell proliferation and cell survival in human cervical cancer HeLa cells. Mol Med Rep. 18:4138–4146. 2018.PubMed/NCBI
32	Kaliki S, Ayyar A, Dave TV, Ali MJ, Mishra DK and Naik MN: Sebaceous gland carcinoma of the eyelid: Clinicopathological features and outcome in Asian Indians. Eye (Lond). 29:958–963. 2015. View Article : Google Scholar : PubMed/NCBI
33	Wang Q, Yang J, Lin X, Huang Z, Xie C and Fan H: Spot14/Spot14R expression may be involved in MSC adipogenic differentiation in patients with adolescent idiopathic scoliosis. Mol Med Rep. 13:4636–4642. 2016. View Article : Google Scholar : PubMed/NCBI
34	Wells WA, Schwartz GN, Morganelli PM, Cole BF, Gibson JJ and Kinlaw WB: Expression of ‘Spot 14’ (THRSP) predicts disease free survival in invasive breast cancer: Immunohistochemical analysis of a new molecular marker. Breast Cancer Res Treat. 98:231–240. 2006. View Article : Google Scholar : PubMed/NCBI
35	Donnelly C, Olsen AM, Lewis LD, Eisenberg BL, Eastman A and Kinlaw WB: Conjugated linoleic acid (CLA) inhibits expression of the Spot 14 (THRSP) and fatty acid synthase genes and impairs the growth of human breast cancer and liposarcoma cells. Nutr Cancer. 61:114–122. 2009. View Article : Google Scholar : PubMed/NCBI
36	Goldstein JL and Brown MS: The LDL receptor. Arterioscler Thromb Vasc Biol. 29:431–438. 2009. View Article : Google Scholar : PubMed/NCBI
37	Basel-Vanagaite L, Zevit N, Har Zahav A, Guo L, Parathath S, Pasmanik-Chor M, McIntyre AD, Wang J, Albin-Kaplanski A, Hartman C, et al: Transient infantile hypertriglyceridemia, fatty liver, and hepatic fibrosis caused by mutated GPD1, encoding glycerol-3-phosphate dehydrogenase 1. Am J Hum Genet. 90:49–60. 2012. View Article : Google Scholar : PubMed/NCBI
38	Lee EK, Lee MJ, Abdelmohsen K, Kim W, Kim MM, Srikantan S, Martindale JL, Hutchison ER, Kim HH, Marasa BS, et al: miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. Mol Cell Biol. 31:626–638. 2011. View Article : Google Scholar : PubMed/NCBI
39	Kim N, Kim JE, Choung HK, Lee MJ and Khwarg SI: Expression of cell cycle regulatory proteins in eyelid sebaceous gland carcinoma: Low p27 expression predicts poor prognosis. Exp Eye Res. 118:46–52. 2014. View Article : Google Scholar : PubMed/NCBI
40	Bell WR, Singh K, Rajan Kd A and Eberhart CG: Expression of p16 and p53 in intraepithelial periocular sebaceous carcinoma. Ocul Oncol Pathol. 2:71–75. 2015. View Article : Google Scholar : PubMed/NCBI
41	Liau JY, Liao SL, Hsiao CH, Lin MC, Chang HC and Kuo KT: Hypermethylation of the CDKN2A gene promoter is a frequent epigenetic change in periocular sebaceous carcinoma and is associated with younger patient age. Hum Pathol. 45:533–539. 2014. View Article : Google Scholar : PubMed/NCBI
42	Li Z, Wang H, Wang Z and Cai H: MiR-195 inhibits the proliferation of human cervical cancer cells by directly targeting cyclin D1. Tumour Biol. 37:6457–6463. 2016. View Article : Google Scholar : PubMed/NCBI
43	Zhong J, Yuan H, Xu X and Kong S: MicroRNA 195 inhibits cell proliferation, migration and invasion by targeting defective in cullin neddylation 1 domain containing 1 in cervical cancer. Int J Mol Med. 42:779–788. 2018.PubMed/NCBI
44	Hui W, Yuntao L, Lun L, WenSheng L, ChaoFeng L, HaiYong H and Yueyang B: MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1. PLoS One. 8:e549322013. View Article : Google Scholar : PubMed/NCBI
45	Liu H, Chen Y, Li Y, Li C, Qin T, Bai M, Zhang Z, Jia R, Su Y and Wang C: miR-195 suppresses metastasis and angiogenesis of squamous cell lung cancer by inhibiting the expression of VEGF. Mol Med Rep. 20:2625–2632. 2019.PubMed/NCBI
46	Ye X and Chen X: miR-149-5p inhibits cell proliferation and invasion through targeting GIT1 in medullary thyroid carcinoma. Oncol Lett. 17:372–378. 2019.PubMed/NCBI
47	Jin L, Li Y, Liu J, Yang S, Gui Y, Mao X, Nie G and Lai Y: Tumor suppressor miR-149-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma. Mol Med Rep. 13:5386–5392. 2016. View Article : Google Scholar : PubMed/NCBI