Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes

Mei-Jie Shi; Huan-Ming Xiao; Yu-Bao Xie; Jun-Min Jiang; Peng-Tao Zhao; Gao-Shu Cai; Ying-Xian Li; Sheng Li; Chao-Zhen Zhang; Min-Ling Cao; Qu-Bo Chen; Zhi-Jian Tan; Heng-Jun Gao; Xiao-Ling Chi

doi:10.1155/2020/5956940

Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes

Evid Based Complement Alternat Med. 2020 Oct 31:2020:5956940. doi: 10.1155/2020/5956940. eCollection 2020.

Authors

Mei-Jie Shi^{1

2}, Huan-Ming Xiao¹, Yu-Bao Xie¹, Jun-Min Jiang¹, Peng-Tao Zhao¹, Gao-Shu Cai¹, Ying-Xian Li¹, Sheng Li¹, Chao-Zhen Zhang¹, Min-Ling Cao¹, Qu-Bo Chen¹, Zhi-Jian Tan¹, Heng-Jun Gao^{3

4}, Xiao-Ling Chi¹

Affiliations

¹ The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China.
² Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
³ National Engineering Center for Biochip at Shanghai, Shanghai 201203, China.
⁴ Institute of Digestive Diseases, School of Medicine, Tongji University, Tongji Hospital Affiliated to Tongji University, Shanghai 200065, China.

Abstract

The aim of this study was to determine if microRNA (miRNA) expression is different among chronic hepatitis B (CHB) patients with early liver fibrosis classified according to traditional Chinese medicine (TCM) syndromes. Eighteen CHB-fibrosis patients and 12 CHB patients without fibrosis were enrolled. The CHB-fibrosis group included 9 patients with the TCM syndrome of Ganyu Pixu Xueyu (GYPXXY), characterized by liver stagnation, spleen deficiency, and blood stasis, and 9 patients with the TCM syndrome of Qixu Xueyu (QXXY), characterized by deficiency of qi, blood, and blood stasis. Agilent miRNA microarray was performed first in liver specimens to determine whether miRNA expression is different in patients with these two TCM syndromes of CHB-fibrosis. Gene Ontology (GO) analysis and KEGG analysis were applied to determine the roles of the differentially expressed miRNAs. QRT-PCR was performed to validate the Agilent miRNA microarray results. Compared with GYPXXY patients, 6 differentially expressed miRNAs were upregulated (miR-144-5p, miR-18a-5p, miR-148b-3p, miR-654-3p, miR-139-3p, and miR-24-1-5p) and 1 was downregulated (miR-6834-3p) in QXXY patients. According to qRT-PCR data, miR-144-5p and miR-654-3p were confirmed as upregulated in CHB-liver fibrosis patients compared to CHB patients without fibrosis, whereas the other 4 miRNAs were not significantly different. More importantly, miR-654-3p was confirmed to be significantly upregulated in QXXY patients compared with values in GYPXXY patients, whereas no significant difference was found in miR-144-5p. Moreover, the pathways of central carbon metabolism in cancer and cell cycle related to miR-654-3p and the target genes of PTEN and ATM were found to be different between QXXY patients and GYPXXY patients. These results indicate that there are different miRNAs, pathways, and target genes between QXXY patients and GYPXXY patients. However, due to the limited sample, whether miR-654-3p and the target genes PTEN and ATM could be molecular markers to differentiate TCM syndromes could not be established.