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Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer

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机构: [1]Department of Medical Oncology, Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001 [2]Department of Respiratory Medicine , Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001 [3]Department of Gynecology and Obstetrics, Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001 [4]Department of Medical Oncology, Hebei Medical University Fourth Hospital, Shijiazhuang, Hebei 050011 [5]Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002 [6]Department of Pathology, Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001 [7]Department of Cytobiology, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
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关键词: miRNA-148a non-small cell lung cancer methylation clinicopathologic characteristics prognostic value

摘要:
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and only 15% of lung cancer patients live more than 5 years. microRNAs (miRNAs) are endogenously expressed non-coding RNAs, and dysregulation of miRNAs is a common feature in human cancers including lung cancer. In this study, we describe the epigenetic regulation of miRNA-148a and its prognostic value in NSCLC. Due to hypermethylation of the miRNA-148a encoding region, the expression levels of miRNA-148a were decreased in NSCLC tissues and cells. Decreased miRNA-148a expression was associated with lymph node metastasis, advanced clinical stage and shortened disease-free survival and overall survival in NSCLC, and was an independent prognostic factor for overall survival in multivariate analysis. In vitro, overexpression of miRNA-148a significantly suppressed the migratory and invasive abilities of A549 and H1299 lung cancer cells. Enforced expression of miRNA-148a in lung cancer cell lines resulted in a significant reduction in the expression of DNMT1. This, in turn, led to a decrease in DNA methylation of the tumor-suppressor gene E-cadherin and induced an increase in the protein levels of E-cadherin. By understanding the function and molecular mechanism of miRNA-148a in NSCLC, miRNA-148a may have therapeutic potential to suppress lung cancer metastasis.

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出版当年[2013]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
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出版当年[2013]版:
Q3 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

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第一作者机构: [1]Department of Medical Oncology, Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001
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通讯机构: [2]Department of Respiratory Medicine , Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001 [5]Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002 [*1]Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, 140 Hanzhong Road, Nanjing, Jiangsu 210002, P.R. China [*2]Department of Respiratory Medicine, Subei People's Hospital, Clinical Medical College of Yangzhou University, No. 98 Nantong West Road, Yangzhou, Jiangsu 225001, P.R. China
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