Correction to: Promoter hypomethylation mediated upregulation of MicroRNA-10b-3p targets FOXO3 to promote the progression of esophageal squamous cell carcinoma (ESCC).

In the original publication of this manuscript [1], Fig. 6 contains a repeated image in error (the left image of 'Migration' and the left image of 'Invasion').

Promoter hypomethylation mediated upregulation of MicroRNA-10b-3p targets FOXO3 to promote the progression of esophageal squamous cell carcinoma (ESCC).

BACKGROUND: Esophageal cancer is a high incident cancer worldwide with poor survival and limited therapeutic options. Alterations of microRNAs are common in cancers, and many of these micro RNAs are potential therapeutic and diagnostic targets to treat these cancers. miR-10b-3p located in chromosome region 2q31.1, and its expression is frequently increased in esophageal squamous cell carcinoma (ESCC). However, the biological functions, clinical significance and therapeutic implications of miR-10b-3p in ESCC remain unclear. METHODS: The expression levels of miR-10b-3p in ESCC specimens were analyzed by in situ hybridization (ISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Ectopic overexpression of miR-10b-3p in ESCC cells, mouse xenograft model, and metastasis model were used to evaluate the effects of miR-10b-3p on proliferation, and migration of cancer cells. Luciferase reporter assay and Western blot were performed to validate the potential targets of miR-10b-3p after the preliminary screening by computer-aided microarray analysis. RESULTS: We found that miR-10b-3p expression levels were significantly upregulated in the tumor tissues and serum samples of patients with ESCC. The expression levels of miR-10b-3p in both tumor tissues and serum samples were inversely associated with lymph node metastasis and clinical stages. We identified the expression level of miR-10b-3p in ESCC cancer samples as an independent prognostic marker of the overall survival rates of ESCC patients. We found more frequent hypomethylation of the CpG sites located upstream of the miR-10b-3p gene in the ESCC tissues compared with in the adjacent normal tissues, and the DNA methylation status of miR-10b-3p promoter region inversely correlated with the expression levels of miR-10b-3p. Ectopic overexpression of miR-10b-3p promoted cell proliferation, colony formation, migration and invasion in ESCC. While knockdown of miR-10b-3p had the opposite effects, particularly in promoting apoptosis. Mouse xenograft model confirmed that miR-10b-3p functions as a potent oncogenic miRNA in ESCC, which also promoting ESCC metastasis. Mechanistically, we found miR-10b-3p regulated FOXO3 expression by directly binding to the 3'-untranslated region. And systemic delivery of miR-10b-3p antagomir reduced tumor growth and inhibit FOXO3 protein expression in nude mice. CONCLUSIONS: Collectively, our findings suggested upregulated expression of miR-10b-3p caused by promoter hypomethylation contributed to the progression of ESCC; Thus, miR-10b-3p is a potentially effective biomarker for ESCC that could have further therapeutic implications.

miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2).

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. MicroRNAs (miRNAs) have been indicated as crucial actors in cancer biology. Accumulating evidence suggests that miRNAs can be used as diagnostic and prognostic markers for NSCLC. METHODS: The purpose of this study was to characterize and identify the novel biomarker miR-4317 and its targets in NSCLC. The expression of miR-4317 was analyzed by in situ hybridization (ISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of miR-4317 on proliferation was evaluated through 3-4,5-dimethylthiazol-2-yl-5-3-carboxymethoxyphenyl-2-4-sulfophenyl-2H-tetrazolium (MTS) and colony formation assays, and cell migration and invasion were evaluated through transwell assays. The expression of target proteins and downstream molecules was analyzed by qRT-PCR and western blot. Dual-luciferase reporter assay was used to assess the target genes of miR4317 in NSCLC cells. RESULTS: Our results demonstrated that miR-4317 was downregulated in NSCLC tissues and serum, particularly in lymph node metastasis and advanced clinical stage tissues. Kaplan-Meier survival analysis showed that NSCLC patients with high expression of miR-4317 exhibited better overall survival (OS). Enhanced expression of miR-4317 significantly inhibited proliferation, colony formation, migration and invasion, and hampered cycles of NSCLC cell lines in vitro. Our results suggested that miR-4317 functions by directly targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2). In concordance with in vitro studies, mouse xenograft, lung, and brain metastatic studies validated that miR-4317 functions as a potent suppressor miRNA of NSCLC in vivo. Systemically delivered agomiR-4317 reduced tumor growth and inhibited FGF9 and CCND2 protein expression. Reintroduction of FGF9 and CCND2 attenuated miR-4317-mediated suppression of migration and invasion in NSCLC. CONCLUSIONS: Our results indicate that miR-4317 can reduce NSCLC cell growth and metastasis by targeting FGF9 and CCND2. These findings provide new evidence of miR-4317 as a potential non-invasive biomarker and therapeutic target for NSCLC.