Gastric cancer (GC) is the fourth most common malignant neoplasm and the second leading cause of cancer death. Identification of key molecular signaling pathways involved in gastric carcinogenesis and progression facilitates early GC diagnosis and the development of targeted therapies for advanced GC patients. Emerging evidence has revealed a close correlation between forkhead box (FOX) proteins and cancer development. However, the prognostic significance of forkhead box S1 (FOXS1) in patients with GC and the function of FOXS1 in GC progression remain undefined. In this study, we found that upregulation of FOXS1 was frequently detected in GC tissues and strongly correlated with an aggressive phenotype and poor prognosis. Functional assays confirmed that FOXS1 knockdown suppressed cell proliferation and colony numbers, with induction of cell arrest in the G0/G1 phase of the cell cycle, whereas forced expression of FOXS1 had the opposite effect. Additionally, forced expression of FOXS1 accelerated tumor growth in vivo and increased cell migration and invasion through promoting epithelial–mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, the core promoter region of FOXS1 was identified at nucleotides −660~ +1, and NFKB1 indirectly bind the motif on FOXS1 promoters and inhibit FOXS1 expression. Gene set enrichment analysis revealed that the FOXS1 gene was most abundantly enriched in the hedgehog signaling pathway and that GLI1 expression was significantly correlated with FOXS1 expression in GC. GLI1 directly bound to the promoter motif of FOXS1 and significantly decreased FOXS1 expression. Finally, we found that miR-125a-5p repressed FOXS1 expression at the translational level by binding to the 3′ untranslated region (UTR) of FOXS1. Together, these results suggest that FOXS1 can promote GC development and could be exploited as a diagnostic and prognostic biomarker for GC.

In order to study the role of long non-coding RNAs (lncRNAs) in predicting platinum-based chemoresistance in patients with high-grade serous ovarian carcinoma (HGS-OvCa), a=7-lncRNA signature was developed by analyzing 561 microarrays and 136 specimens from RNA-sequencing (RNA-seq) obtained from online databases [odds ratio (OR), 2.859; P0.8). The lncRNA signature was independent of clinical characteristics and 4 HGS-OvCa molecular subtypes. This signature was negatively associated with disease-free survival (n=47; log-rank, P<0.01). Furthermore, the expression of the 7 lncRNAs was consistent with microarray (GSE63885, GSE51373, GSE15372 and GSE9891) and RNA-seq data. In in vitro experiments, ZBED3-AS1, F11-AS1 and GAS5 were differentially expressed in cell lines that are known to be resistant and non-resistant to platinum-based drugs, which was consistent with the results in the present study. This lncRNA signature may be used as a prognostic marker for predicting resistance to platinum-based chemotherapeutics in HGS-OvCa. These findings may contribute to individualized therapies in patients with HGS-OvCa in the future.

Identification of novel clinical biomarker in clear cell renal carcinoma (ccRCC) is warranted. Integrating transcriptome (n=1669), DNA methylation (n=577) and copy number data (n=832), we developed a method to identify driver biomarkers by analyzing the omics-level dynamics of Epithelial-Mesenchymal Transition (EMT)-related genes in ccRCC. We first identified 504 expression dynamic changed genes involved in ccRCC-associated key pathways such as EMT, cell cycle, EGFR and PI3K/AKT signaling. Further analysis identified 229 (90 gene promoters) aberrant expression quantitative trait methylation (eQTM) and 256 genes with expression quantitative trait copy number (eQTCN) alterations. Among them, FOXM1 was affected by both eQTM and eQTCN. FOXM1 copy number amplification (115/500, 23% of patients), occurred in an amplified peak in chromosome 12q13.3, was enriched in late-stage ccRCC samples and was associated with worse survival. FOXM1-overexpressed pT3 patients with distant metastasis showed (similar to)25% shorter overall survival in both training (log-rank P=0.006) and validation (log-rank P=0.018) cohorts. The eQTM-gene hybrid signature (cg00044170 and FOXM1), superior to either gene expression or DNA methylation alone, showed great potential in diagnosing localized ccRCC in training (area under curve = 0.958) and validation datasets. FOXM1 could be a novel prognostic biomarker and shed light for early diagnosis at molecular level in ccRCC.

Purpose: Gastric cancer (GC) is the fifth most common tumor in the world, and most patients with GC have a poor prognosis. This study aimed to explore the biological influence and mechanism of LINC01272 in GC. Materials and Methods: Using bioinformatic analyses, we investigated the expression of LINC01272 in TCGA database and predicted the biological functions and mechanism of LINC01272 in GC. Then, we detected the expression of LINC01272 in GC cell lines, GC tissues, and corresponding normal tissues using real-time polymerase chain reaction (RT-PCR). Finally, we explored the migration and invasion ability of LINC01272 by wound-healing and Transwell assays and examined the expression of epithelial-mesenchymal transition (EMT)-related proteins through Western blotting. Results: We found that LINC01272 was upregulated in GC and was associated with GC staging and lymph node metastasis. The results of wound-healing and Transwell assays revealed that the LINC01272 was closely related to GC cell migration and invasion. LINC01272 knockdown inhibited the migration and invasion ability of GC cells by reducing the expression of EMT-related proteins. Overexpression of LINC01272 had the opposite effect. Conclusion: Together, our results showed that LINC01272 promoted GC metastasis ability by regulating the expression of EMT-related proteins and could serve as a potential diagnostic biomarker for GC.