Increasing evidence has experimentally proved the competitive endogenous RNA (ceRNA) hypothesis that long non-coding RNA (lncRNA) can affect the expression of RNA targets by competitively combining microRNA (miRNA) via miRNA response elements. However, an extensive ceRNA network of thyroid carcinoma in a large cohort has not been evaluated. We analyzed the RNAseq and miRNAseq data of 348 cases of primary papillary thyroid cancer (PTC) patients with clinical information downloaded from The Cancer Genome Atlas (TCGA) project to search for potential biomarkers or therapeutic targets. A computational approach was applied to build an lncRNA-miRNA-mRNA regulatory network of PTC. In total, 780 lncRNAs were detected as collectively dysregulated lncRNAs in all 3 PTC variants compared with normal tissues (fold change >2 and false discovery rate <0.05). The interactions among 45 lncRNAs, 13 miRNAs and 86 mRNAs constituted a ceRNA network of PTC. Nine out of the 45 aberrantly expressed lncRNAs were related to the clinical features of PTC patients. However, the expression levels of 3 lncRNAs (LINC00284, RBMS3-AS1 and ZFX-AS1) were identified to be tightly correlated with the patients overall survival (log-rank, P<0.05). The present study identified a list of specific lncRNAs associated with PTC progression and prognosis. This complex ceRNA interaction network in PTC may provide guidance for better understanding the molecular mechanisms underlying PTC.

Epigenetic abnormalities play a vital role in the progression of ovarian cancer. Lysine-specific demethylase 1 (LSD1/KDM1A) acts as an epigenetic regulator and is overexpressed in ovarian tumors. However, the upstream regulator of LSD1 expression in this cancer remains elusive. Here, we show that epidermal growth factor (EGF) signaling upregulates LSD1 protein levels in SKOV3 and HO8910 ovarian cancer cells overexpressing both LSD1 and the EGF receptor. This effect is correlated with a decrease in the dimethylation of H3K4, a major substrate of LSD1, in an LSD1-dependent manner. We also show that inhibition of PI3K/AKT, but not MEK, abolishes the EGF-induced upregulation of LSD1 and cell migration, indicating that the PI3K/PDK1/AKT pathway mediates the EGF-induced expression of LSD1 and cell migration. Significantly, LSD1 knockdown or inhibition of LSD1 activity impairs both intrinsic and EGF-induced cell migration in SKOV3 and HO8910 cells. These results highlight a novel mechanism regulating LSD1 expression and identify LSD1 as a promising therapeutic target for treating metastatic ovarian cancer driven by EGF signaling.

Epithelial ovarian carcinoma (EOC) is the most lethal gynecologic malignancy. However, the molecular mechanisms remain unclear. In this study, we found that miR-146b was downregulated in EOC and its expression level was negatively correlated with the pathological staging. Follow-up functional experiments illustrated that overexpression of miR-146b significantly inhibited cell migration and invasion, and increased cell proliferation, but it also improved the response to chemotherapeutic agents. Mechanistically, we demonstrated that miR-146b exerted its function mainly through inhibiting F-box and leucine-rich repeat protein 10 (FBXL10), and upregulated the Cyclin D1, vimentin (VIM), and zona-occludens-1 (ZO-1) expression in EOC. These findings indicate that miR-146b–FBXL10 axis is an important epigenetic regulation pathway in EOC. Low miR-146b may contribute to cancer progression from primary stage to advanced stage, and may be the promising therapeutic target of EOC.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. LIN28 homolog A (LIN28A) is a RNA-binding protein, which serves a fundamental role in cell development and pluripotency. Polo-like kinase 4 (PLK4) is a member of the polo-like kinase family, which primarily takes part in the mitotic regulation. Overexpression of LIN28A has been demonstrated in ovarian cancer; however, the expression of PLK4 and the correlation between the expression of LIN28A and PLK4 in EOC has not been discussed. In the present study, the mRNA and protein levels of LIN28A and PLK4 were evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry in ovarian tissues of patients. Results demonstrated significantly increased expression in EOC compared with benign epithelial ovarian tumors. High expression of LIN28A and PLK4 was detected at the advanced pathological stage. Furthermore, PLK4 expression was positively correlated with LIN28A (r=0.555; P=0.039). The median survival analysis of patients with EOC with LIN28A and PLK4 double positive expression was 14 months, compared with 30 months in single positive and 60 months in double negative patients by Kaplan-Meier analysis (P<0.05). The expressions of LIN28A and PLK4 was elevated in different EOC cell lines compared to with a normal ovarian cell line. The 293T cells transfected with LIN28A plus a PLK4 plasmid were the fastest-growing group. These results suggest that co-expression of LIN28A and PLK4 may be associated with poor prognosis of EOC and could serve as promising prognostic biomarkers and therapeutic targets in EOC. LIN28A and PLK4 may be used along with traditional morphological and clinical characteristics for predicting prognosis.

Dynamic changes in metabolites may affect liver disease progression, and provide new methods for predicting liver damage. We used ultra-performance liquid chromatography-mass spectroscopy to assess serum metabolites in healthy controls (HC), and patients with acute hepatitis E (AHE) or hepatitis E virus acute liver failure (HEV-ALF). The principal component analysis, partial least squares discriminant analysis, and discriminant analysis of orthogonal projections to latent structures models illustrated significant differences in the metabolite components between AHE patients and HCs, or between HEV-ALF and AHE patients. In pathway enrichment analysis, we further identified two altered pathways, including linoleic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis, when comparing AHE patients with HCs. Linoleic acid metabolism and porphyrin and chlorophyll metabolism pathways were significantly different in HEV-ALF when compared with AHE patients. The discriminative performances of differential metabolites showed that taurocholic acid, glycocholic acid, glycochenodeoxycholate-3-sulfate, and docosahexaenoic acid could be used to distinguish HEV-ALF from AHE patients. The serum levels of glycocholic acid, taurocholic acid, deoxycholic acid glycine conjugate, and docosahexaenoic acid