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.

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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Chen Y,Min L,Zhang X,Hu S,Wang B,Liu W,Wang R,Gu X,Shen W,Lv H,Zou J,Chen Y,Xu X,Chen L

doi

10.3892/or.2013.2611

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

1832-40

issue

4

eissn

1021-335X

issn

1791-2431

journal_volume

30

pub_type

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