Breast cancer is among the most common malignant cancers in women. B‐cell‐specific Moloney murine leukemia virus integration site 1 (BMI‐1) is a transcriptional repressor that has been shown to be involved in tumorigenesis, the cell cycle, and stem cell maintenance. In our study, increased expression of BMI‐1 was found in both human triple negative breast cancer and luminal A‐type breast cancer tissues compared with adjacent tissues. We also found that knockdown of BMI‐1 significantly suppressed cell proliferation and migration in vitro and in vivo. Further mechanistic research demonstrated that BMI‐1 directly bound to the promoter region of CDKN2D/BRCA1 and inhibited its transcription in MCF‐7/MDA‐MB‐231. More importantly, we discovered that knockdown of CDKN2D/BRCA1 could promote cell proliferation and migration after repression by PTC‐209. Our results reveal that BMI‐1 transcriptionally suppressed BRCA1 in TNBC cell lines whereas, in luminal A cell lines, CDKN2D was the target gene. This provides a reference for the precise treatment of different types of breast cancer in clinical practice.

Background: Ovarian cancer is a common gynecological tumor with high malignant potential and poor prognosis. TRIM8, is involved in the development of various tumors, but its precise regulatory role in ovarian cancer is still unknown.Aims: The aim of this study was to explore the specific mechanism by which TRIM8 regulates ovarian cancer.Materials and Methods: We used bioinformatics analysis to screen for high expression of TRIM8 in ovarian cancer. The expression of TRIM8 in healthy and cancerous ovarian tissues was assessed by immunofluorescence. TRIM8 was silenced or overexpressed in ovarian cancer cell lines, with cell proliferation and migration evaluated by CCK8, transwell and clonal formation assays. The effect of TRIM8 on ovarian cancer cells in vivo was assessed by subcutaneous tumor formation experiments in nude mice. The potential interacting protein VDAC2 was identified by mass spectrometry. The mechanism underlying TRIM8 regulation of VDAC2 was evaluated by co‐immunoprecipitation and western blotting.Results: TRIM8 was overexpressed in ovarian cancer. TRIM8 promoted the proliferation and migration of ovarian cancer cells in vitro and the growth of subcutaneous tumors in mice in vivo. TRIM8 interacted with VDAC2, weakened the stability of the protein, and promoted its polyubiquitination and subsequent degradation. Knockdown of VDAC2 increased the resistance of ovarian cancer cells to iron death, whereas overexpression of VDAC2 attenuated ovarian cancer progression induced by TRIM8 overexpression.Discussion: TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation, these finding may provide new targets for the treatment of ovarian cancer.Conclusion: TRIM8 degraded VDAC2 through the ubiquitination pathway, increased the resistance of ovarian cancer cells to iron death, and promoted the proliferation and migration of ovarian cancer.

Background: Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis, and it is highly heterogeneous. There is growing evidence that the tumor immune microenvironment (TIME) plays a crucial role in tumor development, maintenance, and treatment responses. Notably however, the full effects of the TIME on prognosis, TIME characteristics, and immunotherapy responses in TNBC patients have not been fully elucidated. Methods: Gene Expression Omnibus and The Cancer Genome Atlas data were used to data analysis. Single-cell sequencing and tissue microarray analysis were used to investigate gene expression. The concentrations and distributions of immune cell types were determined and analyzed using the CIBERSORT strategy. Tumor immune dysfunction and exclusion score and the IMvigor210 cohort were used to estimate the sensitivity of TNBC patients with different prognostic statuses to immune checkpoint treatment. Results: Five immune-related genes associated with TNBC prognosis (IL6ST, NR2F1, CKLF, TCF7L2, and HSPA2) was identified and a prognostic evaluation model was constructed based on those genes. The respective areas under the curve of the prognostic nomogram model at 3 and 5 years were 0.791 and 0.859. The group with a lower nomogram score, with a better prognosis survival status and clinical treatment benefit rate. Conclusion: A prognostic model for TNBC that was closely related to the immune landscape and therapeutic responses was constructed. This model may help clinicians to make more precise and personalized treatment decisions pertaining to TNBC patients.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies with poor prognosis. However, the underlying mechanisms of ATC remain to be elucidated. Recently, increasing studies have focused on competitive endogenous RNA (ceRNA) to discover valuable biomarkers for the diagnosis of ATC. The present study identified 705 differentially expressed mRNAs and 47 differentially expressed lncRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also conducted. Additionally, an lncRNA/miRNA/mRNA network was constructed which included 1103 regulatory relations. The upregulation of RP11-395G23.3 in ATC cells was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In the loss of function assays, results suggested silencing of RP11-395G23.3 inhibited cell proliferation and induced cell apoptosis. Mechanically, RP11-395G23.3 could increase ROR1 via sponging miR-124-3p as a ceRNA. Moreover, ROR1 expression was decreased with the downregulation of RP11-395G23.3, but was rescued by the co-transfection of the miR-124-3p inhibitor in ATC cells. Our research suggested that the RP11-395G23.3/miR-124-3p/ROR1 axis potentially acted as a potential target for the diagnosis of ATC.

Despite significant advances made by genome-wide association studies (GWAS) in the genetic exploration of tumors such as thyroid cancer (TC), the precise pathogenic genes and underlying biological mechanisms of TC remain unclear. We performed a transcriptome-wide association study (TWAS) to identify the susceptibility genes for TC. Three complementary methods: FUSION (Functional Summary-based Imputation), FOCUS (Fine-mapping Of CaUsal gene Sets), and Multi-marker Analysis of GenoMic Annotation (MAGMA) were used to validate key gene discoveries. Additionally, MAGMA was used to examine the functional enrichment of single nucleotide polymorphisms (SNPs) associated with TC. Conditional and joint analysis, as well as fine mapping techniques, were employed to deepen our understanding of TC's genetic architecture. To explore causal relationships, we conducted Mendelian randomization analysis, while colocalization analysis was used to provide potential shared SNPs between key genes and TC risk. Through the comprehensive application of three TWAS methods, we identified three potential susceptibility genes closely associated with TC risk. Mendelian randomization analysis provided causal links between the TGFB2, SMAD3 and SDCCAG8 genes and TC. Colocalization analysis further revealed that TGFB2 (rs1764705), SMAD3 (rs17293632), and SDCCAG8 (rs2490395) may share genetic signals between GWAS and expression quantitative trait loci (eQTL), indicating common pathways in TC pathogenesis. The study highlighted differences in the expression of significant genes in normal and thyroid cancer tissues at the transcriptome level and investigated their relationship with the tumor microenvironment. This investigation uncovered three new genes associated with increased TC risk, shedding light on the genetic underpinnings of TC and aiding in a deeper comprehension of its complex genetic architecture.