Integrated Analyses of lncRNA and mRNA Profiles Reveal Characteristic and Functional Changes of Leukocytes in Qi-Deficiency Constitution and Pi-Qi-Deficiency Syndrome of Chronic Superficial Gastritis

Abstract

Objects. To investigate the lncRNA-mediated trans- and cis-regulation of genes expression underlying leukocyte functions and characteristics, especially the leukocyte-related biomarkers implicated in the linkage between traditional Chinese medicine- (TCM-) defined qi-deficiency constitution (QDC) and Pi-qi-deficiency syndrome (PQDS) of chronic superficial gastritis (CSG). Methods. We adopted RNA-sequencing approach to identify differential lncRNAs and genes in leukocytes, clustered expression profiles, and analyzed biological functions and pathways of differential genes to decode their potential roles in contributing to characteristics and functions of leukocytes. In addition, interaction networks were created to detail the interactions between differential genes. In particular, we explored differential lncRNAs-mediated regulation of differential genes and predicted the subcellular location of lncRNAs to reveal their potential roles. Results. Compared with TCM-defined balanced constitution (BC), 183 and 93 genes as well as 749 and 651 lncRNAs were differentially expressed (P<0.05 and |log2 (fold change)| ≥1) in leukocytes of individuals from case populations 1 (QDC) and 2 (PQDS), respectively. Of them, 12 genes and 111 lncRNAs were common to each case population. Several networks were created to detail the interactions among case-specific genes, especially case-specific lncRNAs-mediated regulation of case-specific genes. Also, interaction networks were created for the common lncRNAs and genes. HCL analyses showed that differential genes and lncRNAs, especially the common genes and lncRNAs, kept similar expression patterns in both case populations. Furthermore, function enrichment analyses just indicated the common biological processes, namely, extracellular matrix organization and cell adhesion via plasma membrane adhesion molecules. In addition, most common genes underwent very tight and complex regulation of many trans- and cis-acting lncRNAs. In particular, of them, ADAMTSL5, COL26A1, COL27A1, MSH5, and LOC390937 could be regulated by multiple case-specific and common lncRNAs, including the means that directs binding of the common lncRNAs to their coded proteins. The common changes in the extracellular matrix and integral components of plasma membrane related to cell-cell adhesion/junction and communication may implicate the linkage between QDC and PQDS, contributing to alterations in characteristics and functions of leukocytes. Conclusions. These results may provide new insights into the characteristic and functional changes of leukocytes in QDC and PQDS, especially the mechanism underlying the linkage of QDC to PQDS, with potential leukocytes biomarkers for future application in integrative medicine.