Squalene epoxidase promotes breast cancer progression by regulating CCNB1 protein stability.

BACKGROUND: Breast cancer (BC) is a prevalent malignancy affecting women, characterized by a substantial occurrence rate. Squalene epoxidase (SQLE) is a crucial regulator of ferroptosis and has been associated with promoting cell growth and invasion in different types of human cancers. This study aimed to investigate the functional significance of SQLE in BC and elucidate the underlying molecular mechanisms involved. METHODS: SQLE expression levels in BC tissues were evaluated using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. Cell viability, invasion, migration, and cell cycle distribution were assessed using a combination of assays, including the Cell Counting Kit-8, EdU, colony formation, Transwell, and wound healing assays and flow cytometry analysis. Measurement of intracellular reactive oxygen species (ROS), malondialdehyde assay, and glutathione assay were utilized to investigate ferroptosis. Furthermore, co-immunoprecipitation and immunofluorescence assays were conducted to explore the correlation between SQLE and CCNB1. The in vivo tumor growth was evaluated by conducting a xenograft tumorigenicity assay to investigate the impact of SQLE. RESULTS: SQLE expression was significantly increased in BC, and higher SQLE expression levels were significantly associated with an unfavorable prognosis. In vitro functional assays revealed that the overexpression of SQLE markedly enhanced the proliferation, migration, and invasion capacities of BC cells. Furthermore, SQLE overexpression facilitated tumor growth in nude mice. Mechanistically, SQLE alleviated the ubiquitination modification of CCNB1, leading to enhanced stability of the CCNB1 protein and decreased intracellular ROS levels. Ultimately, this inhibited ferroptosis and facilitated the progression of BC. Our findings have provided insights into a crucial pathway by which elevated SQLE expression confers protection to BC cells against ferroptosis, thus promoting cancer progression. SQLE may serve as a novel oncological marker and a potential therapeutic target for BC progression. CONCLUSIONS: In conclusion, this study provides evidence that SQLE plays a regulatory role in BC progression by modulating CCNB1 and ferroptosis. These findings offer valuable insights into the role of SQLE in the pathogenesis of BC and demonstrate its potential as a therapeutic target for treating BC.

CircSNX25 mediated by SP1 promotes the carcinogenesis and development of triple-negative breast cancer.

Circular RNAs (circRNAs), according to a growing body of research, are thought to be important in the initiation and development of a number of cancers. However, more research is needed to fully understand how circRNAs work at the molecular level in triple-negative breast cancer (TNBC). RNA sequencing was conducted on four sets of TNBC samples and their corresponding adjacent noncancerous tissues (ANTs). The circSNX25 expression was assessed using quantitative real-time PCR in TNBC tissues and cells. Several in vitro and in vivo experiments were conducted in order to examine the function of circSNX25 in TNBC carcinogenesis. Through luciferase reporter and chromatin immunoprecipitation (ChIP) assays, we also investigated the potential regulation of circSNX25 biogenesis by specificity protein 1 (SP1). To further validate the relationship between circSNX25 and COPI coat complex subunit beta 1 (COPB1) in TNBC, we conducted circRNA pull-down and RNA immunoprecipitation (RIP) assays using the MS2/MS2-CP system. Online databases were analyzed to examine the clinical implications and prognostic value of COPB1 in TNBC. A higher circSNX25 expression levels were observed in tissues and cells of TNBC. Silencing circSNX25 notably inhibited TNBC cell proliferation, triggered apoptosis, and hindered tumor growth in vivo. Conversely, upregulation of circSNX25 had the opposite effects. Mechanistically, circSNX25 was found to physically interact with COPB1. Importantly, we identified that SP1 may enhance circSNX25 biogenesis. COPB1 levels were markedly higher in TNBC cells. Analysis of online databases revealed that TNBC patients with elevated COPB1 levels had a poorer prognosis. Our findings demonstrate that SP1-mediated circSNX25 promotes TNBC carcinogenesis and development. CircSNX25 may therefore serve as both a diagnostic and therapeutic biomarker for TNBC patients.

Molecular characteristics and prognosis of breast cancer patients with different level of HER2 positivity after adjuvant and neoadjuvant chemotherapy.

PURPOSE: HER2-low breast cancer (BC) has renewed interests of researchers worldwide. Here, we aimed to investigate the clinicopathological characteristics of patients with HER2-low, HER2-0 and HER2 ultra-low BC and make conclusion. METHODS: We collected cases of patients who were diagnosed as BC at Jingling General hospital. Immunohistochemistry was used to redefine HER2 scores. Kaplan-Meier methods and Cox proportional hazards regression analysis were used to compare survival. RESULTS: We found that HER2-low BC was more frequent in hormone receptor (HR)-positive BC patients and was associated with fewer T3-T4, lower breast conserving surgery rate and higher adjuvant chemotherapy rate. HER2-low BC patients had better overall survival (OS) compared to HER2-0 BC in premenopausal and stage II BC. Furthermore, HER2-0 BC patients had lower Ki-67 expression levels compared to HER2-ultra low and HER2-low BC in HR-negative BC. HER2-0 BC patients also had worse OS rate compared to those with HER2-ultra low BC in HR-positive BC. Finally, HER2-0 BC patients showed a higher pathological response rate compared to those with HER2-low BC after neoadjuvant chemotherapy. CONCLUSIONS: These findings suggest that HER2-low BC has distinct biology and clinical features compared to HER2-0 BC, and more investigation is needed to understand the biology of HER2-ultra low BC.

Polyamine synthesis enzyme AMD1 is closely related to the tumorigenesis and prognosis of human breast cancer.

Adenosylmethionine decarboxylase 1 (AMD1) has been implicated in carcinogenesis and tumor progression. However, the potential biomechanism and biological implications of AMD1 in breast cancer (BC) remain unclear. The purpose of this study was to investigate the effect of abnormal expression of AMD1 in BC. The expression of AMD1 in different human BC cell lines was studied by using western blotting and qRT-PCR. In vitro cell proliferation, clone formation, cell cycle and apoptosis assays were performed to explore the effect of AMD1 on cellular proliferation. Xenograft mouse models were established to elucidate the role of AMD1 in BC growth. The expression profiles of AMD1 in 28 pairs of BC tissues and adjacent noncancerous tissues (ANTs) were investigated by using western blotting and immunohistochemistry. The clinical implication and prognostic evaluation of AMD1 in BC were examined by excavating the online database. We found that the expression levels of AMD1 in BC cell lines were significantly higher than those in the normal human breast epithelial cell line MCF-10A. In addition, AMD1 potentiated proliferation, induced cell cycle progression and inhibited apoptosis in BC cells. Subcutaneous tumor xenografts also supported the promotive role of AMD1 in BC growth. We discovered that the level of AMD1 in BC tissues was significantly higher than that in ANTs. Using the online database, increased AMD1 was found to be associated with clinical indicators and predicted a poor prognosis in patients with BC. Our findings indicate that AMD1 elicits potent oncogenic effects on the malignant progression of BC. AMD1 might serve as a promising diagnostic biomarker and therapeutic target for patients with BC.

Diagnosis and Treatment of Rash Fever with Anxiety.

A patient was admitted to our hospital with irregular rash, fever, fatigue, night sweats, and insomnia. The patient's condition showed no improvements with routine testing and treatments. In this paper, a successful treatment is presented for future therapeutic reference of this type of patient.