Haibo Wang

BACKGROUND: Tumor suppressor microRNA miR-145 is commonly down-regulated in colon carcinoma tissues, but its specific role in tumors remains unknown. METHODS: In this study, the authors identified the Friend leukemia virus integration 1 gene (FLI1) as a novel target of miR-145. FLI1 is involved in t(11;22)(q24:q12) reciprocal chromosomal translocation in Ewing sarcoma, and its expression appears to be associated with biologically more aggressive tumors. RESULTS: The authors demonstrated that miR-145 targets a putative microRNA regulatory element in the 3'-untranslated region (UTR) of FLI1, and its abundance is reversely associated with FLI1 expression in colon cancer tissues and cell lines. By using a luciferase/FLI1 3'-UTR reporter system, they found that miR-145 down-regulated the reporter activity, and this down-regulation was reversed by anti-miR-145. Mutation of the miR-145 microRNA regulatory element sequence in the FLI1 3'-UTR abolished the activity of miR-145. miR-145 decreased FLI1 protein but not FLI1 mRNA, suggesting a mechanism of translational regulation. Furthermore, the authors demonstrated that miR-145 inhibited cell proliferation and sensitized LS174T cells to 5-fluorouracil-induced apoptosis. CONCLUSIONS: Taken together, these results suggest that miR-145 functions as a tumor suppressor by down-regulating oncogenic FLI1 in colon cancer.

Lung squamous carcinoma (LUSC) is the second most frequent subtype of non-small cell lung cancer. Rarely gene alterations are identified in LUSC. Therefore, identifying LUSC-related genes to explain the relevant molecular mechanism is urgently needed. A potential biomarker, calcium-activated nucleotidase 1 (CANT1), was elevated in tissues of LUSC patients relative to normal cases based on the TCGA and/or GTEx database. CCK-8 and transwell tests were then implemented to measure the proliferative, invasive and migratory capacities, and showed that knockdown of CANT1 blocked LUSC cells proliferation. miR-607, predicted as an upstream factor for CANT1, was declined in LUSC using TargetScan analysis and luciferase activity test. Low miR-607 expression was related with unfavorable outcomes of LUSC patients. Moreover, miR-607 downregulation elevated cell viability, invasion and migration in LUSC cells, which was antagonized by si-CANT1. GEPIA website was accessed to estimate the relevance between CANT1 and epithelial-mesenchymal transition (EMT)-related positive factors. The protein levels of Fibronectin, Vimentin, Snail and β-catenin were altered due to the abnormal CANT1 and miR-607 expression. Together, these data unveiled that miR-607/CANT1 pair may exert a vital role in the progression of LUSC through mediating EMT process, which would furnish an available therapeutic therapy for LUSC.

MicroRNAs (miRs), acting as tumor suppressor or oncogenes genes, play a critical role in controlling tumor invasion, metastasis and survival via regulating a variety of targets. MiR-148a has been observed low expressed in several types of human cancers, and overexpression of miR-148a inhibits tumorigenesis. However, the molecular mechanisms of miR-148a-mediated these effects are largely elusive. Therefore, the aim of this study was to evaluate the biological function and molecular insight on miR-148a mediated roles in breast cancer cell. In the present study, we demonstrated that low miR-148a expression was observed in breast cancer cells compared to the normal human breast cells. Transfection with miR-148a inhibited growth, migration, invasion, and induced apoptosis in MDA-MB-231 cells. Ubiquitin-specific protease 4 (USP4) and BIM was the potential target of miR-148a. Indeed, miR-148a overexpression decreased expression of USP4 and increased BIM expression. Additionally, we revealed that miR-148a exerts its pro-apoptotic functions through upregulation of BIM, and miR-148a exerts its anti-invasive functions through downregulation of USP4. We therefore suggested that miR-148a is a tumor suppressor, which could be a promising therapeutic target for breast cancer.