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Regulatory Mechanism of MicroRNA-145 in the Pathogenesis of Acute Aortic Dissection
Tianbo Li,Chencheng Liu,Lingchao Liu,Han Xia,Yingbin Xiao,Xuefeng Wang,Yong Wang 연세대학교의과대학 2019 Yonsei medical journal Vol.60 No.4
Purpose: Previous studies have confirmed that microRNAs play important roles in the pathogenesis of acute aortic dissection(AAD). Here, we aimed to explore the role of miR-145 and its regulatory mechanism in the pathogenesis of AAD. Materials and Methods: AAD tissue samples were harvested from patients with aortic dissection and normal donors. Rat aorticvascular smooth muscle cells (VSMCs) were transfected with miR-145 mimic/inhibitor or negative control mimic/inhibitor. Geneand protein expression was measured in human aortic dissection tissue specimens and VSMCs by qRT-PCR and Western blot. Luciferasereporter assay was applied to verify whether connective tissue growth factor (CTGF) was a direct target of miR-145 inVSMCs. Methyl thiazolyl tetrazolium assay was used to detect VSMC viability. Results: miR-145 expression was downregulated in aortic dissection tissues and was associated with the survival of patients withAAD. Overexpression of miR-145 promoted VSMC proliferation and inhibited cell apoptosis. Moreover, CTGF, which was increasedin aortic dissection tissues, was decreased by miR-145 mimic and increased by miR-145 inhibitor. Furthermore, CTGF wasconfirmed as a target of miR-145 and could reverse the promotion effect of miR-145 on the progression of AAD. Conclusion: miR-145 suppressed the progression of AAD by targeting CTGF, suggesting that a miR-145/CTGF axis may provide apotential therapeutic target for AAD.
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Yu Feng,Yutao Liu,Mingming Yuan,Guilan Dong,Hongxia Zhang,Tongmei Zhang,Lianpeng Chang,Xuefeng Xia,Lifeng Li,Haohua Zhu,Puyuan Xing,Hongyu Wang,Yuankai Shi,Zhijie Wang,Xingsheng Hu 대한암학회 2022 Cancer Research and Treatment Vol.54 No.3
Purpose To investigate the feasibility of biomarkers based on dynamic circulating tumor DNA (ctDNA) to classify small cell lung cancer (SCLC) into different subtypes. Materials and Methods Tumor and longitudinal plasma ctDNA samples were analyzed by next-generation sequencing of 1,021 genes. PyClone was used to infer the molecular tumor burden index (mTBI). Pre-treatment tumor tissues [T1] and serial plasma samples were collected (pre-treatment [B1], after two [B2], six [B3] cycles of chemotherapy and at progression [B4]). Results Overall concordance between T1 and B1 sequencing (n=30) was 66.5%, and 89.5% in the gene of <i>RB1</i>. A classification method was designed according to the changes of <i>RB1</i> mutation, named as subtype Ⅰ (both positive at B1 and B2), subtype Ⅱ (positive at B1 but negative at B2), and subtype Ⅲ (both negative at B1 and B2). The median progressive-free survival for subtype Ⅰ patients (4.5 months [95%CI: 2.6-5.8]) was inferior to subtype Ⅱ (not reached, p<0.0001) and subtype Ⅲ (10.8 months [95%CI: 6.0-14.4], p=0.002). The median overall survival for subtype Ⅰ patients (16.3 months [95%CI: 5.3-22.9]) was inferior to subtype Ⅱ (not reached, p=0.01) and subtype Ⅲ (not reached, p=0.02). Patients with a mTBI dropped to zero at B2 had longer median overall survival (not reached vs. 19.5 months, p=0.01). The changes of mTBI from B4 to B1 were sensitive to predict new metastases, with a sensitivity of 100% and a specificity of 85.7%. Conclusion Monitoring ctDNA based <i>RB1</i> mutation and mTBI provided a feasible tool to predict the prognosis of SCLC.
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Identification of DNA methylation and genetic alteration simultaneously from a single blood biopsy
Chen Xiaomin,Liu Jiahui,Li Jun,Xie Yinpeng,Yu Zichen,Shen Lu,Liu Qingfeng,Wu Wei,Zhao Qiang,Lin Haoxiang,Liu Gaotong,Luo Qiuping,Yang Ling,Huang Yi,Zhao Meiru,Yi Xin,Xia Xuefeng 한국유전학회 2023 Genes & Genomics Vol.45 No.5
Background High-throughput sequencing of blood cell-free DNA (cfDNA) techniques offer an opportunity to characterize and monitor cancer rapidly in a non-invasive and real-time manner. Nonetheless, there lacks a tool within therapeutic arsenal to identify multi-omics alterations simultaneously from a single biopsy. In current times, bisulfite-based sequencing detects 5mC and 5hmC at single-base resolution is the golden standard of DNA methylation, while the degradation of DNA and biased sequencing data are the problems of this method. Objective To identify the consistency analysis of methylation and genetic variation with single library, we presented a platform detecting multi-omics data simultaneously from a single blood biopsy using bisulfite-free method of genomic methylation sequencing (GM-seq) mediated by TET enzyme. Methods We detected methylomic and genetic changes simultaneously from a single blood biopsy in NA12878 and randomly chose ten blood biopsies from colorectal cancer or lung cancer patients to validate the ability of GM-seq. Results Similar cytosine methylation level between whole genome bisulfite sequencing (WGBS) and GM-seq were identified in NA12878. Moreover, longer insert size, CpGs coverage and GC distribution were outperformed than WGBS. In addition, the comparison of the single nucleotide polymorphism (SNP), insertion-deletion (Indel) and copy number variation (CNV) in NA12878 or ctDNA from liver cancer between GM-seq and whole genome sequencing (WGS) show a good consistency, indicating that this method is feasible for detecting genetic variation in blood. Conclusion In conclusion, our work demonstrated a method for identification of the methylated modification and genetic variations simultaneously from a single blood biopsy.
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