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The invasion capability of HCC cells was critically disrupted after the co-knockdown of BTBD7 and HIF-1 , and was moderately decreased when si-BTBD7 or si-HIF-1 was transfected separately (Figure S4). Luciferase assay proved that the transcriptional activity of BTBD7 was abolished under hypoxia by HRE2-mut (PGL3-BTBD7-581M) instead of HRE1-mut (PGL3-BTBD7-1000M) and HRE3-mut (PGL3-BTBD7-40M) (Figure 2C). Dear Editor, This study is the first to demonstrate that HIF-1 could activate BTBD7 under hypoxia, thus promoting HCC metastasis through tumor cell adhesion and EMT. Besides, the overexpression of BTBD7 or HIF-1 enhanced the invasion activity of HepG2 cells and exhibited a combined effect when BTBD7 and HIF-1 were co-overexpressed (Figure 2E). [Extracted from the article]

Alterations of mitogen-activated protein kinase kinase 1 (MEK1) are commonly associated with tumorigenesis, and MEK1 is thought to be a suitable targeted therapy for various cancers. However, abnormal MEK1 alterations and their relevant clinical implications are unknown. Our research comprehensively analyzed the MEK1 alteration spectrum and provided novel insight for targeted therapies. There were 7694 samples covering 32 types of cancer from The Cancer Genome Atlas (TCGA) database. They were used to conduct an integrative analysis of MEK1 expression, alterations, functional impacts and clinical significance. There was a dramatic difference in the alteration frequency and distribution and clinical implications in 32 types of cancer from the TCGA. Skin cutaneous melanoma (SKCM) has the most alterations and has therapeutic targets located in the protein kinase domain, and the growing expression of SKCM is positively related to patient prognosis. MEK1 expression in lung adenocarcinoma (LUAD), kidney renal papillary cell carcinoma (KIRP), esophageal carcinoma (ESCA) and liver hepatocellular carcinoma (LIHC) is decreased, which is associated with better prognosis, while MEK1 expression in thymoma (THYM), stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC), testicular germ cell tumors (TGCTs) and head and neck squamous cell carcinoma (HNSC) is increased, which is associated with better prognosis. Mesothelioma (MESO) has the second highest alterations but has no therapy targets. This study provided a great and detailed interpretation of MEK1 expression, alterations and clinical implications in 32 types of cancer and reminded us to fill the gap in MEK1 research from a new perspective. [ABSTRACT FROM AUTHOR]

BRCA1 interacting helicase 1 (BRIP1) alteration was crucial in tumors and it was a potential therapeutic target in ovarian serous cystadenocarcinoma (OV). Although a small number of studies had focused on BRIP1, an extensive study of BRIP1 genetic mutation and its clinical application in different cancer types had not been analyzed. In the current study, we analyzed BRIP1 abnormal expression, methylation, mutation, and their clinical application via several extensive datasets, which covered over 10,000 tumor samples across more than 30 cancer types. The total mutation rate of BRIP1 was rare in pan cancer. Its alteration frequency, oncogenic effects, mutation, and therapeutic implications were different in each cancer. 242 BRIP1 mutations were found across 32 cancer types. UCEC had the highest alteration (mutation and CNV) frequency. In addition, BRIP1 was a crucial oncogenic factor in OV and BRCA. BRIP1 mutation in PRAD was targetable, and FDA had approved a new drug. Moreover, Kaplan–Meier curve analysis showed that BRIP1 expression and genetic aberrations were closely related to patient survival in several cancers, indicating their potential for application as new tumor markers and therapeutic targets. The current study profiled the total BRIP1 mutation spectrum and offered an extensive molecular outlook of BRIP1 in a pan cancer analysis. And it suggested a brand-new perspective for clinical cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) seriously threatens women's life. Ferroptosis plays an essential role in the initiation and development of OC. However, more molecular targets and mechanisms for ferroptosis in OC remain to be further elucidated.Methods: Several OC datasets were integrated in this study and three candidate genes including PRNP were further screened out as the ferroptosis-related gene which was differentially expressed in OC. Then, comprehensive evaluations concerning gene expression, clinical implication, in vitro validation of expression and functional experiments, prediction of downstream molecules and related signal pathways, and immune-modulating function were performed.Results: PRNP was the only downregulated ferroptosis-related gene with prognostic value for OC patients. The decreased mRNA and protein expression was verified in OC tissues and cell lines. PRNP was significantly correlated with cancer stages, primary therapy outcomes, and age in OC patients. Moreover, we found that overexpression of PRNP inhibited the proliferation, migration, and invasion ability of OC cells through in vitro experiments. PRNP was enriched to the Ras signaling pathway. PRNP expression was positively correlated with the infiltration of immune cells, such as mast cells, T effector memory cells, plasmacytoid DC cells, NK cells, and eosinophils. In addition, the association of PRNP with other immune signatures was also found.Conclusion: This study demonstrated for the first time showed that ferroptosis-related gene PRNP exerted a tumor suppressive role in OC and the aberrant expression and function of PRNP making it a potential novel biomarker for OC diagnosis, prognosis, and response to immunotherapies. [ABSTRACT FROM AUTHOR]

Background. All YTH domain family members are m6A reader proteins accounting for the methylation modulation involved in the process of tumorgenesis and tumor progression. However, the expression profiles and roles of the YTH domain family in lung adenocarcinoma (LUAD) remain to be further illustrated. Methods. GEPIA2 and TNMplot databases were used to generate the expression profiles of the YTH family. Kaplan-Meier plotter database was employed to analysis the prognostic value of the YTH family. Coexpression profiles and genetic alterations analysis of the YTH family were undertaken using the cBioPortal database. YTH family protein-associated protein-protein interaction (PPI) network was identified by using STRING. Functional enrichment analysis was performed with the help of the WebGestalt database. The correlation analysis between the YTH family and immune cell infiltration in LUAD was administrated by using the TIMER2.0 database. Results. mRNA expression of YTHDC1 and YTHDC2 was significantly lower in LUAD, whereas YTHDF1, YTHDF2, and YTHDF3 with apparently higher expression. YTHDF2 expression was observed to be the highest in the nonsmoker subgroup, and its expression gradually decreased with the increased severity of smoking habit. LUAD patients with low expression of YTHDC2, YTHDF1, and YTHDF2 were correlated with a better overall survival (OS) time. The YTHDF1 genetic alteration rate was 26%, which was the highest in the YTH family. The major cancer-associated functions of YTH family pointed in the direction of immunomodulation, especially antigen processing and presentation. Most of the YTH family members were significantly correlated with the infiltration of CD4+ T cells, CD8+ T cells, macrophages, and neutrophils, indicating the deep involvement of the YTH domain family in the immune cell infiltration in LUAD. Conclusion. The molecular and expression profiles of the YTH family were dysregulated in LUAD. YTH family members (especially YTHDC2) were promising biomarkers and potential therapeutic targets that may bring benefit for the patients with LUAD. [ABSTRACT FROM AUTHOR]