MicroRNA-1253 suppresses cell proliferation and invasion of non-small-cell lung carcinoma by targeting WNT5A.
Meiyue LiuYue ZhangJie ZhangHaifeng CaiChao ZhangZhao YangYi NiuHuan WangXiaomei WeiWei WangPeng GaoHongmin LiJinghua ZhangGuogui SunPublished in: Cell death & disease (2018)
MicroRNAs (miRNA) are a class of small, noncoding RNA molecules that regulate the expression of target genes. miRNA dysregulation is involved in carcinogenesis and tumor progression. In this study, we identified microRNA-1253 (miR-1253) as being significantly down-regulated in non-small-cell lung carcinoma (NSCLC) tissues and associated with advanced clinical stage, lymph node metastasis, and poor survival. The enhanced expression of miR-1253 significantly inhibited the proliferation, migration, and invasion of NSCLC cells in vitro. Bioinformatics analyses showed that miR-1253 directly targeted WNT5A (long isoform), which was confirmed using the dual-luciferase reporter assay. The inhibitory effects of miR-1253 on the growth and metastasis of NSCLC cells were attenuated and phenocopied by WNT5A (long) overexpression and knockdown, respectively. Consistent with the in vitro results, subcutaneous tumor and metastatic NSCLC mouse models showed that miR-1253 functions as a potent suppressor of NSCLC in vivo. Taken together, our findings indicated that miR-1253 inhibited the proliferation and metastasis of NSCLC cells by targeting WNT5A (long isoform) and provided new evidence of miR-1253 as a potential therapeutic target in NSCLC.
Keyphrases
- cell proliferation
- small cell lung cancer
- long non coding rna
- poor prognosis
- long noncoding rna
- advanced non small cell lung cancer
- stem cells
- lymph node metastasis
- single cell
- squamous cell carcinoma
- brain metastases
- pi k akt
- cell therapy
- mouse model
- cell cycle arrest
- mesenchymal stem cells
- gene expression
- risk assessment
- crispr cas
- epidermal growth factor receptor
- cell death
- bone marrow
- genome wide identification