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

Chen,Yong; Min,Lingfeng; Zhang,Xizhi; Hu,Suwei; Wang,Buhai; Liu,Wei; Wang,Rui; Gu,Xuewen; Shen,Weigan; Lv,Houning; Zou,Jing; Chen,Yuexiang; Xu,Xingxiang; Chen,Longbang

doi:10.3892/or.2013.2611

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

Authors:
- Yong Chen
- Lingfeng Min
- Xizhi Zhang
- Suwei Hu
- Buhai Wang
- Wei Liu
- Rui Wang
- Xuewen Gu
- Weigan Shen
- Houning Lv
- Jing Zou
- Yuexiang Chen
- Xingxiang Xu
- Longbang Chen
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Affiliations: Department of Medical Oncology, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Respiratory Medicine, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Gynecology and Obstetrics, Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Medical Oncology, Hebei Medical University Fourth Hospital, Shijiazhuang, Hebei 050011, P.R. China, Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China, Department of Pathology, Subei People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Cytobiology, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
Published online on: July 9, 2013 https://doi.org/10.3892/or.2013.2611
Pages: 1832-1840

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Abstract

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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