{"doi":"10.3390/cells9102175","title":"Integrated Transcriptome and Proteome Analyses Reveal the Regulatory Role of miR-146a in Human Limbal Epithelium via Notch Signaling","abstract":"MiR-146a is upregulated in the stem cell-enriched limbal region vs. central human cornea and can mediate corneal epithelial wound healing. The aim of this study was to identify miR-146a targets in human primary limbal epithelial cells (LECs) using genomic and proteomic analyses. RNA-seq combined with quantitative proteomics based on multiplexed isobaric tandem mass tag labeling was performed in LECs transfected with miR-146a mimic vs. mimic control. Western blot and immunostaining were used to confirm the expression of some targeted genes/proteins. A total of 251 differentially expressed mRNAs and 163 proteins were identified. We found that miR-146a regulates the expression of multiple genes in different pathways, such as the Notch system. In LECs and organ-cultured corneas, miR-146a increased Notch-1 expression possibly by downregulating its inhibitor Numb, but decreased Notch-2. Integrated transcriptome and proteome analyses revealed the regulatory role of miR-146a in several other processes, including anchoring junctions, TNF-α, Hedgehog signaling, adherens junctions, TGF-β, mTORC2, and epidermal growth factor receptor (EGFR) signaling, which mediate wound healing, inflammation, and stem cell maintenance and differentiation. Our results provide insights into the regulatory network of miR-146a and its role in fine-tuning of Notch-1 and Notch-2 expressions in limbal epithelium, which could be a balancing factor in stem cell maintenance and differentiation.","journal":"Cells","year":2020,"id":69994,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":370741,"name":"Mangesh Kulkarni","orcid":"0000-0003-3872-9772","position":1,"is_corresponding":false},{"id":226030,"name":"Aleksandra Leszczynska","orcid":"0000-0002-8005-2657","position":2,"is_corresponding":false},{"id":293223,"name":"Jie Tang","orcid":"0000-0002-3991-2539","position":3,"is_corresponding":false},{"id":370742,"name":"Ruchi Shah","orcid":"0000-0002-9533-1747","position":4,"is_corresponding":false},{"id":344710,"name":"Yasaman Jami‐Alahmadi","orcid":"0000-0001-8289-2222","position":5,"is_corresponding":false},{"id":370743,"name":"Jason Wang","orcid":"0000-0002-0758-3523","position":6,"is_corresponding":false},{"id":243810,"name":"Andrei A. Kramerov","orcid":null,"position":7,"is_corresponding":false},{"id":14958,"name":"James A. Wohlschlegel","orcid":"0000-0003-3399-901X","position":8,"is_corresponding":false},{"id":370744,"name":"Vasu Punj","orcid":"0000-0002-4598-3202","position":9,"is_corresponding":false},{"id":241437,"name":"Alexander V. Ljubimov","orcid":"0000-0003-2398-5319","position":10,"is_corresponding":false},{"id":372571,"name":"Mehrnoosh Saghizadeh","orcid":null,"position":11,"is_corresponding":false},{"id":372570,"name":"Adam J. Poe","orcid":null,"position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-18T21:43:11.119231Z","pmid":"32993109","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}