AIMGestational diabetes mellitus is common during pregnancy, impacting maternal health and fetal development. The aim of this study was to identify potential long non-coding RNAs (lncRNAs) and mRNAs in gestational diabetes mellitus.METHODSThe placenta tissues from four women patients with gestational diabetes mellitus and three healthy pregnant women were used for RNA sequencing. Differentially expressed lncRNAs and mRNAs were obtained. Then, interaction networks of lncRNA-nearby targeted mRNA and lncRNA-co-expressed mRNA were constructed, followed by functional annotation of co-expressed mRNAs. Third, GSE51546 dataset was utilized to validate the expression of selected co-expressed mRNAs. In addition, in vitro experiment was applied to expression validation of lncRNAs and mRNAs. Finally, GSE70493 dataset was utilized for diagnostic analysis of selected co-expressed mRNAs.RESULTSA total of 78 differentially expressed lncRNAs and 647 differentially expressed mRNAs in gestational diabetes mellitus were obtained. Several interaction pairs of lncRNA-co-expressed mRNA including LINC01504-CASP8, FUT8-AS1-TLR5/GDF15, GATA2-AS1-PQLC3/KIAA2026, and EGFR-AS1-HLA-G were identified. Endocytosis (involved HLA-G) and toll-like receptor signaling pathway (involved TLR5 and CASP8) were remarkably enriched signaling pathways of co-expressed mRNAs. It is noted that CASP8, TLR5, and PQLC3 had a significant prognosis value for gestational diabetes mellitus.CONCLUSIONSOur study identified several differentially expressed lncRNAs and mRNAs, and their interactions, especially co-expression, may be associated with gestational diabetes mellitus.