Abstract
MicroRNA-449a is expressed at a low level in several tumors and cancer cell lines, and induces G1 arrest, apoptosis, and senescence. To identify the function of miR-449a in non-small cell lung cancer (NSCLC), we discussed the potential relevance of miR-449a to clinicopathological characteristics and prognosis in NSCLC. We also investigated the impact of miR-449a on migration and invasion in NSCLC cells. The expression of miR-449a in NSCLC tissues and cell lines was detected using RT-qPCR. In vitro, gain-of-function, loss-of-function experiments, and fluorescence assays were performed to identify the potential target of miR-449a and the function of miR-449a in NSCLC cells. MiR-449a was downregulated in both NSCLC tissues and cell lines. Moreover, a low expression level of miR-449a appeared to be correlated with lymph node metastasis and poor survival. In vitro, miR-449 regulated cell migration and invasion in NSCLC cells as a potential tumor suppressor, at least in part by targeting c-Met. Furthermore, reciprocal expression of miR-449a and c-Met was shown in NSCLC tissue samples. This study indicates that miR-449a might be associated with NSCLC progression, and suggests a crucial role for miR-449a in NSCLC.
Highlights
MicroRNAs are a class of small non-coding RNAs, approximately 20 to 25 nucleotides, which regulate gene expression posttranscriptionally
We found that miR-449a was significantly downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, consistent with the report that miR449 was reduced in several human tumors and cancer cell lines [16]
Jeon and colleagues found that miR-449a/b has reduced expression in lung cancer tissues, with the target gene histone deacetylase 1 (HDAC1) overexpressed at mRNA level [15]
Summary
MicroRNAs (miRNAs) are a class of small non-coding RNAs, approximately 20 to 25 nucleotides, which regulate gene expression posttranscriptionally. 50% of human miRNAs are located at fragile sites and genomic regions involved in cancers [1]. Emerging evidence shows that miRNAs are correlated with various human cancers and function as both oncogenes and tumor suppressors [2,3,4]. MicroRNA expression deregulation in human cancers have shown that miRNA dysregulation is associated with many cancers including lung cancer [5,6,7,8,9]. Raponi and colleagues described distinct miRNA expressions in lung squamous cell carcinoma (SCC) compared with normal lung tissue [11]. Based on miRNA expression deregulation, miRNAs could provide a novel method for cancer diagnosis
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