SummaryLectin-like oxidized LDL receptor-1 (LOX-1) is a surface scavenger receptor for oxidized low-density lipoprotein (oxLDL). Several transcription factors have been reported to regulate LOX-1 expression. MicroRNAs are small noncoding RNAs that control gene expression, but there have been no reports of LOX-1 expression being regulated by microRNAs. Because the microRNA let-7g has been predicted to bind to LOX-1 mRNA, we investigated whether let-7g can regulate LOX-1 expression. Our experiments first demonstrated that oxLDL can reduce let-7g expression. We later confirmed that there is a let-7g binding site on the 39-untranslated region of LOX-1 mRNA. We showed that intracellular Ca 2+ -activated protein kinase C is involved in the oxLDL-LOX-1-let-7g pathway. Bioinformatics predicted that the let-7g promoter has a binding site for the transcriptional repressor OCT-1. We used a promoter assay and chromatin immunoprecipitation to confirm this binding. Consequently, knockdown of OCT-1 was found to increase let-7g expression. Transfection of let-7g inhibited oxLDL-induced LOX-1 and OCT-1 expression, cell proliferation and migration. Mice fed with a high-fat diet showed a decrease in let-7g and an increase in LOX-1 and OCT-1. A study on humans showed the serum levels of let-7g are lower in subjects with hypercholesterolemia compared with normal controls. Our findings identify a negative feedback regulation between let-7g and LOX-1, and indicate that let-7g could be a target to treat cardiovascular disease.

This study showed that microRNA-93 can inhibit tumorigenesis and reduce the recurrence of CRC; these findings may have potential clinical applications for predicting the recurrence of CRC.

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PURPOSE. Fibroblast growth factor-10 (FGF10) can modulate extracellular matrix associated genes and, therefore, it could be a myopia susceptibility gene. This study used an animal model, single nucleotide polymorphisms (SNPs) association, and genetic functional assay to evaluate FGF10 gene for myopia. METHODS.The expression levels of FGF10 gene were compared among the form deprivation myopic (FDM) eyes, the fellow eyes of the FDM group, and the healthy eyes of experimental mice. In the present study 1020 cases ( À6.0 diopters [D]) and 960 controls ( ‡À1.5 D) were enrolled from a Chinese population. Eight tagging SNPs were genotyped to test for an association between genotypes and myopia. The luciferase reporter assay was conducted for the particular SNP to assess the allelic effect on gene expression. RESULTS.The sclera of FDM eyes had a 2.57-fold higher level of FGF10 mRNA (P ¼ 0.018) than the fellow eyes. Although no SNP was associated with high myopia, SNP rs339501 was significantly associated with extreme myopia ( À10 D, P ¼ 0.008) and the odds ratio (OR) was 1.58 for G allele carriers. The luciferase assay showed that the risk G allele significantly caused a higher expression level than the A allele (P ¼ 0.011).CONCLUSIONS. The evidence suggested FGF10 to be a risk factor for myopia. The sclera of myopic eyes had higher FGF10 levels. The risk G allele of SNP rs339501 was associated with extreme myopia in human and caused a higher gene expression in the luciferase assay. It is concluded that the FGF10 could have been involved in the development of myopia.Keywords: FDM, myopia, FGF10 M yopia is a common eye condition worldwide, and its prevalence varies widely among populations and ages and between the sexes.1-3 When the definition of less than À6 diopters (D) was used, the prevalence of high myopia was found to be 18% among young Taiwanese men and 24% among young Taiwanese women 1 ; both of which are higher than the 13.1% reported among young men in Singapore.2 Furthermore, an increased frequency of high myopia (<À6.0 D) was found in young Taiwanese people: 10.9% in 1983 and 21% in 2000. 4 Myopia progresses quickly in childhood, especially around the teenage years. By early adulthood, the rate of change in ocular refraction tends to decline and the prevalence of myopia stabilizes. 5 Several studies have also shown the family history of myopia to be a significant risk factor. 6,7 Recently, genetic association studies including genome-wide association studies (GWAS) have reported several susceptibility genes to nonsyndromic myopia. 8-17Scleral remodeling is one of the important mechanisms for the development of myopia, 18 Several genes are associated with the scleral remodeling including sulfated glycosaminoglycans (GAGs), 19 matrix metalloproteinases (MMPs), 20 tissue inhibitors of metalloproteinases (TIMPs), 20 and TGF-b. 21 The expression of fibroblast growth factor 10 (FGF10) has been shown to be abundant in the murine retina and sclera. 22,23 FGF10 plays a pivotal role in controlling elongation of lacrima...

Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death. By performing miRNA microarray and bioinformatics analyses, we observed that expression of 248 miRNAs was altered, including five significantly upregulated and 17 significantly downregulated miRNAs, in TMZ-treated U87MG cells. miR-128 expression levels were lower in different glioma cells and strongly associated with poor survival. TMZ treatment significantly upregulated miR-128 expression. TMZ significantly enhanced miR-128-1 promoter activity and transcriptionally regulated miR-128 levels through c-Jun N-terminal kinase 2/c-Jun pathways. The overexpression and knockdown of miR-128 expression significantly affected TMZ-mediated cell viability and apoptosis-related protein expression. Furthermore, the overexpression of miR-128 alone enhanced apoptotic death of glioma cells through caspase-3/9 activation, poly(ADP ribose) polymerase degradation, reactive oxygen species generation, mitochondrial membrane potential loss, and non-protective autophagy formation. Finally, we identified that key members in mammalian target of rapamycin (mTOR) signaling including mTOR, rapamycin-insensitive companion of mTOR, insulin-like growth factor 1, and PIK3R1, but not PDK1, were direct target genes of miR-128. TMZ inhibited mTOR signaling through miR-128 regulation. These results indicate that miR-128-inhibited mTOR signaling is involved in TMZ-mediated cytotoxicity. Our findings may provide a better understanding of cytotoxic mechanisms of TMZ involved in glioblastoma development.