Xueli Li

BACKGROUND: Friend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. However, little is known about the mechanisms underlying the activation of this proto-oncogene in tumors. RESULTS: Immunohistochemical staining showed that FLI1 is aberrantly overexpressed in advanced stage and metastatic breast cancers. Using a CRISPR Cas9-guided immunoprecipitation assay, we identify a circular RNA in the FLI1 promoter chromatin complex, consisting of FLI1 exons 4-2-3, referred to as FECR1.Overexpression of FECR1 enhances invasiveness of MDA-MB231 breast cancer cells. Notably, FECR1 utilizes a positive feedback mechanism to activate FLI1 by inducing DNA hypomethylation in CpG islands of the promoter. FECR1 binds to the FLI1 promoter in cis and recruits TET1, a demethylase that is actively involved in DNA demethylation. FECR1 also binds to and downregulates in trans DNMT1, a methyltransferase that is essential for the maintenance of DNA methylation. CONCLUSIONS: These data suggest that FECR1 circular RNA acts as an upstream regulator to control breast cancer tumor growth by coordinating the regulation of DNA methylating and demethylating enzymes. Thus, FLI1 drives tumor metastasis not only through the canonical oncoprotein pathway, but also by using epigenetic mechanisms mediated by its exonic circular RNA.

BACKGROUND: RRM1, the regulatory subunit of ribonucleotide reductase, is involved in carcinogenesis, tumor progression, and the response of non-small-cell lung cancer to treatment. METHODS: We developed an automated quantitative determination of the RRM1 protein in routinely processed histologic specimens. In these specimens, we measured the expression of RRM1 and two other proteins that are relevant to non-small-cell lung cancer: the excision repair cross-complementation group 1 (ERCC1) protein and the phosphatase and tensin homologue (PTEN). We compared the results with the clinical outcomes in 187 patients with early-stage non-small-cell lung cancer who had received only surgical treatment. RESULTS: RRM1 expression correlated with the expression of ERCC1 (P<0.001) but not with the expression of PTEN (P=0.37). The median disease-free survival exceeded 120 months in the group of patients with tumors that had high expression of RRM1 and was 54.5 months in the group with low expression of RRM1 (hazard ratio for disease progression or death in the high-expression group, 0.46; P=0.004). The overall survival was more than 120 months for patients with tumors with high expression of RRM1 and 60.2 months for those with low expression of RRM1 (hazard ratio for death, 0.61; P=0.02). Among these 187 patients, the survival advantage was limited to the 30% of patients with tumors that had a high expression of both RRM1 and ERCC1. CONCLUSIONS: RRM1 and ERCC1 are determinants of survival after surgical treatment of early-stage, non-small-cell lung cancer.

functions as a critical epigenetic player in the regulation of mitochondrial metabolism of hepatoma cells, laying the foundation for further clarifying the roles of lncRNAs in tumor metabolic reprogramming.

Polycystic ovary syndrome (PCOS) is one of the most prevalent reproductive disorders in women worldwide. Despite rigorous research, the exact molecular mechanism that governs PCOS pathogenesis remains unclear. To investigate the potential roles of circular RNAs (circRNAs), this study sequenced ribosomal RNA-depleted total RNA from exosomes of follicle fluids obtained from PCOS patients using non-PCOS samples as controls. Bioinformatic analysis identified 167 upregulated and 245 downregulated circRNAs from a total of 16,771 detected candidates. Functional analysis suggests that pathways related to bacterial infection, associated chronic inflammation, and oxidative stress could be targeted by the differential circRNAs in PCOS patients. The obtained sequencing results were further validated by quantitative reverse-transcription polymerase chain reaction and a circRNA-microRNA interaction network was constructed. The obtained results provide a valuable addition to the published studies on the mechanism of PCOS pathogenesis by revealing a wide variety of new circRNAs, miRNA, and gene targets that merit further investigation.

The feature analysis of epileptic EEG is very significant in diagnosis of epilepsy. This paper introduces two nonlinear features derived from fractal geometry for epileptic EEG analysis. The features of blanket dimension and fractal intercept are extracted to characterize behavior of EEG activities, and then their discriminatory power for ictal and interictal EEGs are compared by means of statistical methods. It is found that there is significant difference of the blanket dimension and fractal intercept between interictal and ictal EEGs, and the difference of the fractal intercept feature between interictal and ictal EEGs is more noticeable than the blanket dimension feature. Furthermore, these two fractal features at multi-scales are combined with support vector machine (SVM) to achieve accuracies of 97.58% for ictal and interictal EEG classification and 97.13% for normal, ictal and interictal EEG classification.