Abstract

Background Constitution in traditional Chinese medicine (TCM) plays a key role in the genesis, development, and prognosis of diseases. Phlegm-dampness constitution (PDC) is one of the nine constitutions in TCM, susceptible to metabolic disorders, which is mainly manifested by profuse phlegm, loose abdomen, and greasy face. Epidemiologic, genomic, and epigenetic studies have been carried out in previous works, confirming that PDC represents a distinctive population with microcosmic changes related to metabolic disorders. However, whether long noncoding RNAs (lncRNAs) play a regulatory role in metabolic disease in subjects with PDC remains largely unknown. We aimed to investigate distinct lncRNA and mRNA expression signatures and lncRNA-mRNA regulatory networks in the phlegm-dampness constitution (PDC). Methods The peripheral blood mononuclear cells (PBMCs) were isolated from the subjects with PDC (n = 13) and balanced constitution (BC) (n = 9). The profiles of lncRNAs and mRNAs in PBMCs were analyzed using microarray and further validated with RT-qPCR. Subsequently, pathway analysis was performed to investigate the function of differentially expressed mRNAs by using Ingenuity Pathway Analysis (IPA). Results Results suggested that some mRNAs, which were regulated by the differentially expressed lncRNAs, were mainly enriched in lipid metabolism and immune inflammation-related pathways. This was consistent with the molecular characteristics of previous studies, indicating that the clinical characteristics of metabolic disorders in PDC might be regulated by lncRNAs. Furthermore, by making coexpression network construction as well as cis-regulated target gene analysis, several lncRNA-mRNA pairs with potential regulatory relationships were identified by bioinformatic analyses, including RP11-317J10.2-CA3, RP11-809C18.3-PIP4K2A, LINC0069-RFTN1, TTTY15-ARHGEF9, and AC135048.13-ORAI3. Conclusions This study first revealed that the expression characteristics of lncRNAs/mRNAs may be potential biomarkers, indicating that the distinctive physical and clinical characteristics of PDC might be partially attributed to the specific expression signatures of lncRNAs/mRNAs.

Highlights

  • Constitution in traditional Chinese medicine (TCM) plays a key role in the genesis, development, and prognosis of diseases

  • To determine the transcriptome characteristics and which long noncoding RNAs (lncRNAs) could be used to Phlegm-dampness constitution (PDC) from those with balanced constitution (BC), we surveyed the lncRNA and mRNA expression profiles of subjects with a total of 22 samples from PDC (n = 13) and BC (n = 9) using microarray analysis (NCBI GEO accession number GSE158042)

  • By combining the lncRNA-mRNA coexpression network and the targets of lncRNA in upstream or downstream 300 kb of lipid metabolism and immune inflammation-related pathways, we identified a total of 12 lncRNA transcripts and their predicted regulatory proteincoding genes (0:7) (Figure 3(b))

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Summary

Introduction

Constitution in traditional Chinese medicine (TCM) plays a key role in the genesis, development, and prognosis of diseases. Results suggested that some mRNAs, which were regulated by the differentially expressed lncRNAs, were mainly enriched in lipid metabolism and immune inflammation-related pathways This was consistent with the molecular characteristics of previous studies, indicating that the clinical characteristics of metabolic disorders in PDC might be regulated by lncRNAs. by making coexpression network construction as well as cisregulated target gene analysis, several lncRNA-mRNA pairs with potential regulatory relationships were identified by bioinformatic analyses, including RP11-317J10.2-CA3, RP11-809C18.3-PIP4K2A, LINC0069-RFTN1, TTTY15-ARHGEF9, and AC135048.13-ORAI3. This study first revealed that the expression characteristics of lncRNAs/mRNAs may be potential biomarkers, indicating that the distinctive physical and clinical characteristics of PDC might be partially attributed to the specific expression signatures of lncRNAs/mRNAs. Constitution in traditional Chinese medicine (TCM) plays an important role in the initiation, development, and prognosis of diseases.

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