PMID- 34787641 OWN - NLM STAT- MEDLINE DCOM- 20211210 LR - 20240404 IS - 1552-5783 (Electronic) IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 62 IP - 14 DP - 2021 Nov 1 TI - Long Noncoding RNA 3632454L22Rik Contributes to Corneal Epithelial Wound Healing by Sponging miR-181a-5p in Diabetic Mice. PG - 16 LID - 10.1167/iovs.62.14.16 [doi] LID - 16 AB - PURPOSE: This work explores the abnormal expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) in diabetic corneal epithelial cells (CECs) and constructs an associated competitive endogenous RNA (ceRNA) network. Moreover, we revealed that Rik may exert advantageous effects on diabetic corneal epithelial wound closure by sponging miR-181a-5p. METHODS: We obtained the profiles of differentially expressed lncRNAs (DELs) of CECs of type 1 diabetic versus control corneas by microarray and summarized the differentially expressed miRNAs (DEmiRs) and differentially expressed genes (DEGs) data by published literature. Subsequently, the ceRNA network was constructed using bioinformatics analyses. The levels of lncRNA ENSMUST00000153610/3632454L22Rik (Rik) and miR-181a-5p were verified. The localization of Rik was identified with fluorescence in situ hybridization (FISH), and dual-luciferase assays proved the targeted relationship between Rik and miR-181a-5p. Furthermore, we validated the functional impact of Rik in vitro. RESULTS: Overall, 111 upregulated and 117 downregulated DELs were detected in diabetic versus control CECs. The level of Rik located in both the cytoplasm and the nucleus was clearly downregulated, whereas miR-181a-5p was upregulated in vitro and in vivo in the diabetic group versus the control group. Rik can act as a ceRNA to bind to miR-181a-5p, thus promoting diabetic corneal epithelial wound healing in vitro. CONCLUSIONS: This work investigated the expression profile of DELs and constructed ceRNA networks of diabetic CECs for the first time. Furthermore, we revealed that Rik may positively impact diabetic corneal epithelial wound healing by sponging miR-181a-5p, providing a novel potential therapeutic target of diabetic keratopathy (DK). FAU - Chen, Xiaxue AU - Chen X AD - Department of Ophthalmology, Fujian Medical University Union Hospital, Fu Zhou, China. FAU - Hu, Jianzhang AU - Hu J AD - Department of Ophthalmology, Fujian Medical University Union Hospital, Fu Zhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Blood Glucose) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Messenger) RN - 0 (mirn181 microRNA, mouse) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Animals MH - Blood Glucose/metabolism MH - Cell Line MH - Diabetes Mellitus, Experimental/*physiopathology MH - Diabetes Mellitus, Type 1/physiopathology MH - Epithelium, Corneal/*physiology MH - Gene Expression Regulation/*physiology MH - Gene Regulatory Networks MH - In Situ Hybridization, Fluorescence MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics MH - Protein Array Analysis MH - Protein Serine-Threonine Kinases/*genetics MH - RNA, Long Noncoding/*genetics MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Transfection MH - Up-Regulation MH - Wound Healing/*physiology PMC - PMC8606839 COIS- Disclosure: X. Chen, None; J. Hu, None EDAT- 2021/11/18 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/11/17 CRDT- 2021/11/17 12:23 PHST- 2021/11/17 12:23 [entrez] PHST- 2021/11/18 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/11/17 00:00 [pmc-release] AID - 2778087 [pii] AID - IOVS-21-33486 [pii] AID - 10.1167/iovs.62.14.16 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2021 Nov 1;62(14):16. doi: 10.1167/iovs.62.14.16.