Abstract
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.
Highlights
Lung cancer is a major cause of death, primarily due to its high incidence, aggressiveness, and lack of effective treatments[1]
Results miR-1253 is down-regulated in Non-small-cell lung carcinoma (NSCLC) and predicts a poor prognosis To explore the expression of miR-1253 in lung cancer, we first analyzed the expression levels of miR-1253 in 70 pairs of human NSCLC tissues and matched non-cancer lung tissues by real-time reverse transcriptase PCR
The results showed that compared to the non-neoplastic lung tissues, miR-1253 expression was significantly down-regulated in the NSCLC tissues (p < 0.05, Fig. 1a, Table 1), especially in the cases with advanced clinical stages (p < 0.05, Fig. 1b, Table 1) and lymph node metastasis (p < 0.05, Fig. 1c, Table 1)
Summary
Lung cancer is a major cause of death, primarily due to its high incidence, aggressiveness, and lack of effective treatments[1]. Prognosis of lung cancer remains poor due to the high rates of metastasis, recurrence, and drug resistance[4]. Official journal of the Cell Death Differentiation Association. Dozens of miRNAs (such as miR-143/145, miR-21, and miR-34) have been shown to play essential roles in lung tumorigenesis by regulating critical oncogenes or tumor suppressors[15,16,17]. MiR195 expression is reduced in tumor tissues and associated with poor survival outcomes[18]. High levels of miR-135b and low levels of miR-590-5p have been associated with clinical stage and survival[14, 19]
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