Long noncoding RNA RP11-356J5.12 promotes ADSCs apoptosis to suppress its effect on repairing diabetic wound via sponging miR-558/BCL2L11 as a ceRNA

Background: Although adipose-derived stem cells (ADSCs) are considered as a novel tissue regenerative technique in diabetes wound, apoptosis in ADSCs limits its application. Long non-coding RNAs (LncRNAs) are crucial for various human diseases while its potential functions and mechanisms are largely unknown in ADSCs therapy for diabetic wound. The aim of the present study was to investigate the potential role of lncRNA RP11-356J5.12 in ADSC apoptosis induced by high glucose. Methods: The effects of high glucose on ADSC apoptosis were evaluated. The differentially expressed lncRNAs were identified from RNA-sequencing data, and RP11-356J5.12 was determined as a new candidate lncRNA. qRT-PCR was used to detect the expression of lncRNAs, miRNAs and mRNAs in ADSCs. RNA immunoprecipitation (RIP), RNA pull-down and luciferase assays were used to detect the interaction of the specific lncRNA, miRNA and mRNA. The effects of RP11-356J5.12 on ADSCs cells apoptosis were explored by flow cytometer, TUNEL assay and Western blot. Diabetic wound was established to explore the function of RP11-356J5.12 on ADSCs repairing ability in vivo. Results: ADSCs subjected to high glucose stress showed a significant increase of lncRNA RP11-356J5.12 expression with obvious induction of apoptosis. Forced expression of RP11-356J5.12 aggravated high glucose induced ADSCs apoptosis in vitro. Mechanistically, RP11-356J5.12 could directly interact with miR-558, and subsequently act as a miRNA sponge to regulate the expression of the miR-558 target gene BCL2L11, which triggered the apoptosis of ADSCs. Furthermore, diabetic wound model showed that RP11-356J5.12 impaired the repair ability of ADSCs in diabetic wound. Conclusions: These data defined RP11-356J5.12/miR-558/BCL2L11 regulatory networks may be a novel therapeutic target for ADSCs in repairing diabetics wound.