Identification and regulation pattern analysis of long noncoding RNAs in meibomian gland carcinoma
Abstract
Aim: To identify long noncoding RNAs (lncRNAs) and to elucidate regulation patterns of lncRNAs in meibomian gland carcinoma (MGC). Materials & methods: We used RNA-Seq, gene ontology, ClueGO, Ingenuity Pathway Analysis and co-expression network analyses to profile the expression and regulation patterns of lncRNAs and mRNAs in MGC. Results: We identified 500 lncRNAs and 326 mRNAs as differentially expressed. Co-expression regulatory networks with lncRNAs and mRNAs were constructed. The differentially expressed mRNAs and lncRNAs were enriched by fundamental biological functions that are implicated in the inflammatory signaling pathway and tumor proliferation (IL6 and PTGS2). Conclusion: LncRNAs might play important roles via the competing endogenous RNA regulation pattern in MGC tumorigenesis and contribute to the molecular pathogenesis of MGC.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1 Effect of androgen deficiency on the human meibomian gland and ocular surface. J. Clin. Endocrinol. Metab. 85(12), 4874–4882 (2000).Medline, CAS, Google Scholar
- 2 . Identification of genes associated with tumorigenesis of meibomian cell carcinoma by microarray analysis. Genomics 90(5), 559–566 (2007).Crossref, Medline, CAS, Google Scholar
- 3 . Sebaceous carcinoma of the ocular region: a review. Surv. Ophthalmol. 50(2), 103–122 (2005).Crossref, Medline, Google Scholar
- 4 . Incidence and survival of sebaceous carcinoma in the United States. J. Am. Acad. Dermatol. 75(6), 1210–1215 (2016).Crossref, Medline, Google Scholar
- 5 . A retrospective review of 1349 cases of sebaceous carcinoma. Cancer 115(1), 158–165 (2009).Crossref, Medline, Google Scholar
- 6 . Sebaceous gland carcinoma of the eyelid: clinicopathological features and outcome in Asian Indians. Eye 29(7), 958–963 (2015).Crossref, Medline, CAS, Google Scholar
- 7 . Forehead galeal pericranial flap for single-staged total upper eyelid reconstruction in sebaceous gland carcinoma excision. Int. Med. Case Rep. J. 10, 309–312 (2017).Crossref, Medline, Google Scholar
- 8 . Ocular sebaceous gland carcinoma: an update of the literature. Int. Ophthalmol.
doi:10.1007/s10792-018-0925-z (2018) (Epub ahead of print). • Up-to-date review about ocular sebaceous gland carcinoma.Crossref, Google Scholar - 9 MicroRNA and transcriptome analysis in periocular sebaceous gland carcinoma. Sci. Rep. 8(1), 7531 (2018). •• Outlined the miRNA and mRNA expression profile in periocular sebaceous gland carcinoma.Crossref, Medline, Google Scholar
- 10 Identification of novel target proteins in sebaceous gland carcinoma. Head Neck 35(5), 642–648 (2013).Crossref, Medline, Google Scholar
- 11 Distinct pathways in the pathogenesis of sebaceous carcinomas implicated by differentially expressed microRNAs. JAMA Ophthalmol. 133(10), 1109–1116 (2015).Crossref, Medline, Google Scholar
- 12 miRNA-200c and miRNA-141 as potential prognostic biomarkers and regulators of epithelial-mesenchymal transition in eyelid sebaceous gland carcinoma. Br. J. Ophthalmol. 101(4), 536–542 (2017).Crossref, Medline, Google Scholar
- 13 . LncRNAs and cancer. Oncol. Lett. 12(2), 1233–1239 (2016).Crossref, Medline, Google Scholar
- 14 . A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146(3), 353–358 (2011). •• An important review regarding competing endogenous RNA hyphothesis.Crossref, Medline, CAS, Google Scholar
- 15 . Integrated analysis of differentially expressed profiles and construction of a competing endogenous long non-coding RNA network in renal cell carcinoma. PeerJ 6, e5124 (2018).Crossref, Medline, Google Scholar
- 16 . TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25(9), 1105–1111 (2009).Crossref, Medline, CAS, Google Scholar
- 17 Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protoc. 7(3), 562–578 (2012).Crossref, Medline, CAS, Google Scholar
- 18 Prediction of novel long non-coding RNAs based on RNA-Seq data of mouse Klf1 knockout study. BMC Bioinformatics 13, 331 (2012).Crossref, Medline, CAS, Google Scholar
- 19 Genome-wide analysis of long noncoding RNA profiling in PRRSV-infected PAM cells by RNA sequencing. Sci. Rep. 7(1), 4952 (2017).Crossref, Medline, Google Scholar
- 20 CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine. Nucleic Acids Res. 35, W345–W349 (2007).Crossref, Medline, Google Scholar
- 21 . CPAT: coding-potential assessment tool using an alignment-free logistic regression model. Nucleic Acids Res. 41(6), e74 (2013).Crossref, Medline, CAS, Google Scholar
- 22 . Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells. Nature 555(7694), 107–111 (2018).Crossref, Medline, CAS, Google Scholar
- 23 . The domain structure and distribution of Alu elements in long noncoding RNAs and mRNAs. RNA 22(2), 254–264 (2016).Crossref, Medline, CAS, Google Scholar
- 24 . RIsearch: fast RNA-RNA interaction search using a simplified nearest-neighbor energy model. Bioinformatics 28(21), 2738–2746 (2012).Crossref, Medline, CAS, Google Scholar
- 25 . RNAplex: a fast tool for RNA-RNA interaction search. Bioinformatics 24(22), 2657–2663 (2008).Crossref, Medline, CAS, Google Scholar
- 26 Widespread transcription at neuronal activity-regulated enhancers. Nature 465(7295), 182–187 (2010).Crossref, Medline, CAS, Google Scholar
- 27 . Noncoding transcription at enhancers: general principles and functional models. Ann. Rev. Genet. 46, 1–19 (2012).Crossref, Medline, CAS, Google Scholar
- 28 . Enhancer RNAs and regulated transcriptional programs. Trends Biochem. Sci. 39(4), 170–182 (2014).Crossref, Medline, CAS, Google Scholar
- 29 . Human microRNA targets. PLoS Biol. 2(11), e363 (2004).Crossref, Medline, Google Scholar
- 30 miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res. 37, D98–D104 (2009).Crossref, Medline, CAS, Google Scholar
- 31 DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA: mRNA interactions. Nucleic Acids Res. 43, D153–D159 (2015).Crossref, Medline, CAS, Google Scholar
- 32 . starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 42, D92–D97 (2014).Crossref, Medline, CAS, Google Scholar
- 33 . miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 43, D146–D152 (2015).Crossref, Medline, CAS, Google Scholar
- 34 . miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res. 37, D105–D110 (2009).Crossref, Medline, CAS, Google Scholar
- 35 miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 42, D78–D85 (2014).Crossref, Medline, CAS, Google Scholar
- 36 . The role of site accessibility in microRNA target recognition. Nat. Genet. 39(10), 1278–1284 (2007).Crossref, Medline, CAS, Google Scholar
- 37 Identification of lncRNA-associated competing triplets reveals global patterns and prognostic markers for cancer. Nucleic Acids Res. 43(7), 3478–3489 (2015).Crossref, Medline, CAS, Google Scholar
- 38 . miRcode: a map of putative microRNA target sites in the long non-coding transcriptome. Bioinformatics 28(15), 2062–2063 (2012).Crossref, Medline, CAS, Google Scholar
- 39 . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4(1), 44–57 (2009).Crossref, Medline, Google Scholar
- 40 . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37(1), 1–13 (2009).Crossref, Medline, Google Scholar
- 41 ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25(8), 1091–1093 (2009).Crossref, Medline, CAS, Google Scholar
- 42 . CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinformatics 29(5), 661–663 (2013).Crossref, Medline, CAS, Google Scholar
- 43 Integrative genomics viewer. Nat. Biotechnol. 29(1), 24–26 (2011).Crossref, Medline, CAS, Google Scholar
- 44 . Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief. Bioinform. 14(2), 178–192 (2013).Crossref, Medline, CAS, Google Scholar
- 45 Long non-coding RNA DILC suppresses cell proliferation and metastasis in colorectal cancer. Gene 666, 18–26 (2018).Crossref, Medline, CAS, Google Scholar
- 46 . Cellular model of colon cancer progression reveals signatures of mRNAs, miRNA, lncRNAs, and epigenetic modifications associated with metastasis. Cancer Res. 77(8), 1854–1867 (2017).Crossref, Medline, CAS, Google Scholar
- 47 Novel long non-coding RNA GACAT3 promotes gastric cancer cell proliferation through the IL-6/STAT3 signaling pathway. Tumour Biol. 37(11), 14895–14902 (2016).Crossref, Medline, CAS, Google Scholar
- 48 . Conjunctival melanoma: association of cyclooxygenase-2 tumor expression to prognosis. Graefe's Arch. Clin. Exp. Ophthalmol. 256(5), 989–995 (2018).Crossref, Medline, CAS, Google Scholar
- 49 Downregulation of HOTAIR expression mediated anti-metastatic effect of artesunate on cervical cancer by inhibiting COX-2 expression. PLoS ONE 11(10), e0164838 (2016).Crossref, Medline, Google Scholar
- 50 Clinical relevance of cyclooxygenase 2 and peroxisome proliferator-activated receptor gamma in eyelid sebaceous gland carcinoma. Histopathology 69(2), 268–275 (2016).Crossref, Medline, Google Scholar
- 51 . Long non-coding RNAs: insights into functions. Nat. Rev. Genet. 10(3), 155–159 (2009). •• Describes the functions of long noncoding RNAs.Crossref, Medline, CAS, Google Scholar
- 52 . The multilayered complexity of ceRNA crosstalk and competition. Nature 505(7483), 344–352 (2014).Crossref, Medline, CAS, Google Scholar
- 53 . Emerging roles of competing endogenous RNAs in cancer: insights from the regulation of PTEN. Mol. Cell. Biol. 33(20), 3976–3982 (2013).Crossref, Medline, CAS, Google Scholar
- 54 . Circular RNA and miR-7 in cancer. Cancer Res. 73(18), 5609–5612 (2013).Crossref, Medline, CAS, Google Scholar
- 55 Circular RNA: a new star of noncoding RNAs. Cancer Lett. 365(2), 141–148 (2015).Crossref, Medline, CAS, Google Scholar
- 56 Competing endogenous RNA networks in human cancer: hypothesis, validation, and perspectives. Oncotarget 7(12), 13479–13490 (2016). • Describes the relationship between competing endogenous RNAs and cancers.Crossref, Medline, Google Scholar
- 57 A computationally constructed ceRNA interaction network based on a comparison of the SHEE and SHEEC cell lines. Cell. Mol. Biol. Lett. 21, 21 (2016).Crossref, Medline, Google Scholar
- 58 The pseudogene DUXAP8 promotes non-small-cell lung cancer cell proliferation and invasion by epigenetically silencing EGR1 and RHOB. Mol. Ther. 25(3), 739–751 (2017).Crossref, Medline, CAS, Google Scholar
- 59 Detection of long-chain non-encoding RNA differential expression in non-small cell lung cancer by microarray analysis and preliminary verification. Mol. Med. Rep. 11(3), 1925–1932 (2015).Crossref, Medline, CAS, Google Scholar
- 60 . Construction of differential mRNA-lncRNA crosstalk networks based on ceRNA hypothesis uncover key roles of lncRNAs implicated in esophageal squamous cell carcinoma. Oncotarget 7(52), 85728–85740 (2016).Crossref, Medline, Google Scholar
- 61 LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner. J. Hematol. Oncol. 9(1), 117 (2016).Crossref, Medline, CAS, Google Scholar

