title: 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.
authors.affiliation: Department of Medical Oncology, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Min
authors.forename: Xizhi
authors.initials: X
authors.lastname: Zhang
authors.forename: Suwei
authors.initials: S
authors.lastname: Hu
authors.forename: Buhai
authors.initials: B
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Xuewen
authors.initials: X
authors.lastname: Gu
authors.forename: Weigan
authors.initials: W
authors.lastname: Shen
authors.forename: Houning
authors.initials: H
authors.lastname: Lv
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.forename: Yuexiang
authors.initials: Y
authors.lastname: Chen
authors.forename: Xingxiang
authors.initials: X
authors.lastname: Xu
authors.forename: Longbang
authors.initials: L
authors.lastname: Chen
mesh_terms: D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D013534:Survival; D016896:Treatment Outcome
chemical_list: D015820:Cadherins; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human