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

作者：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^*

来源：Oncology Reports, 2013, 30(4): 1832-1840.

DOI：10.3892/or.2013.2611

• miRNA-148a
• non-small cell lung cancer
• methylation
• clinicopathologic characteristics
• prognostic value

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.

• 出版日期2013-10
• 单位河北医科大学; 扬州大学; 南京大学