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.

Leiming You,Anlong Xu,Kunyu Li,Xinhui Gao,Aijie Liu,Ting Wang,Wei Wang,Xiaopu Sang,Ting’An Li,Guangrui Huang,Shen Zhang

doi:10.1155/2020/8518053

Abstract

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.

Highlights

Traditional Chinese medicine (TCM) is an ancient medical practice system with the longest history in Asia [1]
12 common genes and 111 common Long noncoding RNAs (lncRNAs) were found in the case populations (Figure 1(a)), considered as the leukocyte candidate biomarkers implicated in Qi-deficiency constitution (QDC) and Pi-qi-deficiency syndrome (PQDS) of chronic superficial gastritis (CSG)
GNAO1 and PCDHGC5 were governed by multiple trans-acting lncRNAs, which were matched in the other two pathways related to cell-cell adhesion and communication, namely, cholinergic synapse pathway and cadherin signaling pathway (Figure 4(e)). These results suggested that the PQDS-specific lncRNAs seemed to be crucial in the regulation of expression profile of PQDS-specific genes, especially the expression regulation of genes in multiple pathways associated with complement and coagulation cascades as well as cell-cell adhesion/junction and communication, which contributed to the characteristics and functions of leukocytes in CSG patients of PQDS

Summary

Introduction

Traditional Chinese medicine (TCM) is an ancient medical practice system with the longest history in Asia [1]. Qi, pronounced “chee,” means energy in TCM. TCM-defined constitution is innate and relatively stable, relying on the intrinsic characteristics of body. It can be influenced by postnatal environment and defined by integrating the morphological structure and physiological function with psychological state [2,3,4,5]. Qi-deficiency constitution (QDC) is one of nine typical body constitutions defined in TCM [3, 4]. Following TCM theories, especially the clinical data, individuals with QDC seem to have a tendency toward the Pi-qi-deficiency syndrome (PQDS), one of the commonly matched TCM syndromes in patients with chronic superficial gastritis (CSG) [6,7,8]. Long noncoding RNAs (lncRNAs), a type of noncoding RNAs (ncRNAs) longer than 200 nucleotides, have been reported to be involved in multiple pathological processes such as inflammation, carcinogenesis, and tumor progression [12,13,14,15]

Results

Discussion

Conclusion