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This study aimed to investigate the expression of Friend leukemia virus integration 1 (Fli-1) and its correlation with the prognosis of endometrial cancer (EC). Thirty-two EC tissue samples were evaluated for Fli-1 expression using immunohistochemistry. Fli-1 showed significantly high expression in EC cells, followed by hyperplasia cells, and was negative in adjacent normal tissues. The high expression of Fli-1 was significantly associated with a high differentiation grade, mutated P53 expression, and histological subtype (p < .05). Downregulation of Fli-1 in AN3CN cells using RNA interference inhibited cell clone formation and proliferation but did not affect apoptosis and migration of the cells. This study provides the first evidence that Fli-1 expression gradually increases in parallel with disease progression, and its overexpression might predict poor prognosis in EC.

Background. Head and neck squamous cell carcinoma (HNSCC) is a growing concern worldwide, due to its poor prognosis, low responsiveness to treatment, and drug resistance. Since immunotherapy effectively improves HNSCC patients' survival status, it is important to continuously explore new immune-related predictive factors to accurately predict the immune landscape and clinical outcomes of individuals suffering from HNSCC. Methods. The HNSCC transcriptome profiling of RNA-sequencing data was retrieved from TCGA database, and the microarray of GSE27020 was obtained from the GEO database for validation. The differentially expressed genes (DEGs) between HNSCC and normal samples were identified by multiple test corrections in TCGA database. The univariate and multivariate Cox analyses were performed to identify proper immune-related genes (IRGs) to construct a risk model. The Cox regression coefficient was employed for calculation of the risk score (RS) of IRG signature. The median value of RS was utilized as a basis to classify individuals with HNSCC into high- and low-risk groups. The Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves were employed for the identification of the prognostic significance and precision of the IRG signature. The signature was also evaluated based on clinical variables, predictive nomogram, mutation analysis, infiltrating immune cells, immune-related pathways, and chemotherapeutic efficacy. The protein-protein interaction (PPI) network and functional enrichment pathway investigations were utilized to explore possible potential molecular mechanisms. Finally, the hub gene's differential mRNA expression levels were evaluated by means of the Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA) was utilized for the validation of their translational levels. Results. Collectively, 1593 DEGs between HNSCC and normal samples were identified, of which 136 IRGs were differentially expressed. Then, the 136 immune-related DEGs were mostly enriched in the cytokine-related signaling pathways by GO and KEGG analyses. After that, a valuable signature based on seven genes (DKK1, GAST, IGHM, IL12RB2, SLURP1, STC2, and TNFRSF4) was designed. The HNSCC patients into the low-risk group and the high-risk group were divided by using the median RS; the HNSCC patients in the high-risk group had a worse survival than those in the low-risk group. The risk signature was verified to be an independent predictive marker for HNSCC patients. Meanwhile, the RS had the largest contribution to survival of these patients based on the predictive nomogram. In addition, the low-risk HNSCC patients exhibited significantly enriched immune cells, along with an association with high chemosensitivity. Conclusion. The constructed gene signature can independently function as a predictive indicator for the clinical features of HNSCC patients. The low-risk HNSCC subjects might benefit from immunotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Intestinal stem cells (ISCs) at the crypt base are responsible for the regeneration of the intestinal epithelium. However, how ISC self‐renewal is regulated still remains unclear. Here we identified a circular RNA, circBtnl1, that is highly expressed in ISCs. Loss of circBtnl1 in mice enhanced ISC self‐renewal capacity and epithelial regeneration, without changes in mRNA and protein levels of its parental gene Btnl1. Mechanistically, circBtnl1 and Atf4 mRNA competitively bound the ATP‐dependent RNA helicase Ddx3y to impair the stability of Atf4 mRNA in wild‐type ISCs. Furthermore, ATF4 activated Sox9 transcription by binding to its promoter via a unique motif, to enhance the self‐renewal capacity and epithelial regeneration of ISCs. In contrast, circBtnl1 knockout promoted Atf4 mRNA stability and enhanced ATF4 expression, which caused Sox9 transcription to potentiate ISC stemness. These data indicate that circBtnl1‐mediated Atf4 mRNA decay suppresses Sox9 transcription that negatively modulates self‐renewal maintenance of ISCs. Synopsis: Intestinal stem cells (ISCs) at the crypt base are responsible for the regeneration of intestinal epithelium. This study shows that a circular RNA, circBtnl1, negatively regulates the self‐renewal maintenance of ISCs in vivo. CircBtnl1 knockout enhances self‐renewal capacity of intestinal stem cells and epithelial regeneration in mice.CircBtnl1 and Atf4 mRNA competitively bind Ddx3y RNA helicase to modulate Atf4 mRNA stability.ATF4 activates Sox9 transcription by binding onto its promoter, which enhances self‐renewal maintenance of intestinal stem cells. [ABSTRACT FROM AUTHOR]

Low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) play a pivotal role by regulating plasma low-density lipoprotein cholesterol (LDL-c) levels. Dihydromyricetin (DMY), the most abundant natural flavonoid in rattan tea, has proven anti-atherogenic effects, but the underlying molecular mechanisms remain poorly understood. Therefore, we studied the effects of DMY on LDLR and PCSK9. The results showed DMY promoted LDLR protein and mRNA expression and increased LDL uptake in HepG2 cells. DMY inhibited intracellular PCSK9 protein and mRNA expression. And it also significantly reduced PCSK9 levels in the cell culture medium. Furthermore, DMY inhibited the expression of PCSK9 through the liver nuclear transcription factor 1 A (HNF1A) and increased the protein expression of LDLR. Taken together, our results support the idea that DMY regulates LDL-c metabolism through PCSK9/LDLR signaling. This study reveals the potential mechanism of DMY's anti-atherogenic effect and provides a theoretical basis for dietary DMY supplementation. [ABSTRACT FROM AUTHOR]

Most of NF-κB (nuclear factor kappa B) signaling molecules have various types of post-translational modifications. In this study, we focused on ubiquitination and designed a siRNA library including most ubiquitin-binding domains. With this library, we identified several candidate regulators of canonical NF-κB pathway, including RNF4. Overexpression of RNF4 impaired NF-κB activation in a dose-dependent manner, whereas RNF4 knockdown potentiated NF-κB activation. We showed that RNF4 interacts with the TAK1–TAB2–TAB3 complex, but not TAB1. Further, we found that RNF4 specifically down-regulated TAB2 through a lysosomal pathway, and knockdown of RNF4 impaired endogenous TAB2 degradation. Therefore, our findings will provide new insights into the negative regulation of NF-κB signaling. [ABSTRACT FROM AUTHOR]