Exosomal miR-151-3p in saliva: A potential non-invasive marker for gastric cancer diagnosis and prognosis modulated by Sijunzi decoction (SJZD) in mice
Ping Yang,
Huijun Lei,
Yue Fu,
Cheng Chen,
Li Tang,
Shuaishuai Xia,
Yan Guo,
Guangyu Chen,
Mengzhou Xie,
Jingjing Yang,
Feng Li,
Liang Li
Affiliations
Ping Yang
Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
Huijun Lei
Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
Yue Fu
Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
Cheng Chen
Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
Li Tang
Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
Shuaishuai Xia
Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
Yan Guo
Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
Guangyu Chen
Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
Mengzhou Xie
Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
Jingjing Yang
Community Health Service Center of Dongtang Street, Yuhua District, Changsha, Hunan, 410004, China
Feng Li
School of Dentistry, University of California, Los Angeles, Los Angeles, CA90095, United States; Corresponding author.
Liang Li
Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Corresponding author. Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China.
Gastric cancer (GC) is one of the most prominent malignancies that originate in the epithelial cells of the gastric mucosa and is one of the main causes of cancer-related mortality worldwide. New circulating biomarkers of exosomal RNA might have great potential for non-invasive early prognosis of GC. Sijunzi Decoction (SJZD) is a typical representative formula of the method of benefiting Qi and strengthening the spleen in Traditional Chinese Medicine (TCM). However, the effects and mechanism of SJZD in treating GC remain unclear. This study looked for biomarkers of exosomal RNA for early prognosis of GC, and explored the mechanism of SJZD in treating GC. A gastric cancer model with spleen deficiency syndrome was established in nude mice, and the curative effects of SJZD were investigated. Differentially expressed miRNAs in plasma and saliva exosomes were sequenced and analyzed. Potential target genes of these miRNAs were predicted and applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment annotation. Overlapping miRNAs in saliva and plasma samples were analyzed, and qRT-PCR was performed for verification. miR-151a-3p was selected, and qRT-PCR further determined that miR-151a-3p was downregulated in saliva and plasma exosomes from the SJZD group. The intersected miR-151a-3p target genes were predicted and enriched in the extrinsic apoptotic signaling pathways. SJZD significantly ameliorates gastric cancer with spleen deficiency syndrome in mouse models, and exosomal miRNAs, particularly miR-151-3p, might be modulated by SJZD in plasma and saliva. The exosomal miR-151-3p in saliva may serve as a non-invasive potential marker for gastric cancer diagnosis and prognosis.
