Neddylation inhibitor MLN4924 enhances H3K18 lactylation via binding to LDH and downregulates ITGB4 to block metastasis.

MLN4924, a small molecule neddylation inhibitor and a potent anti-cancer agent, was previously shown to has some neddylation-independent effects. Whether MLN4924 regulates histone lactylation in neddylation-dependent or independent manner is previously unknown. We reported here that MLN4924 significantly increased the lactate levels by activating lactate dehydrogenase (LDH) activity via inducing LDH tetramerization to promote histone H3K18 lactylation in breast cancer cells.

Presentation of endometrial vascular dystrophy under narrow-band imaging: Two case reports and literature review.

Rationale: Endometrial vascular dystrophy is a rare and poorly understood pathological condition characterized by tortuous and dilated blood vessels visible under hysteroscopy. Diagnosing this condition is challenging due to its potential resemblance to more severe lesions, such as endometrial hyperplasia or carcinoma. Narrow-band imaging (NBI) technology enhances the visualization of superficial vascular structures, offering a new perspective for diagnosis.

Single-cell RNA-seq reveals as a prognostic biomarker in low-grade endometrial stromal sarcoma.

Background: Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine malignancy characterized by its complex tumor microenvironment (TME) and high recurrence rates, posing challenges to accurate prognosis and effective treatment. Identifying prognostic biomarkers is essential for improving patient stratification and guiding therapeutic strategies.

Methods: Using single-cell transcriptome analysis combined with H&E and multiplex immunofluorescence staining, we identified a subpopulation of tumor cells in LG-ESS and further validated the association of this subpopulation and its characteristic genes with LG-ESS prognosis by molecular characterization and bulk transcriptome data.

The learning curve of laparoscopic single-site salpingectomy with conventional laparoscopic instruments: A retrospective cohort study.

Tubal pregnancy is a common cause of maternal mortality in early pregnancy. Transumbilical laparoendoscopic single-site surgery (TU-LESS) has gained popularity due to its safety and aesthetic advantages. However, the lack of affordable disposable entry platforms hinders its widespread adoption.

Circ_0078607 increases platinum drug sensitivity via miR-196b-5p/GAS7 axis in ovarian cancer.

Platinum-based chemotherapy is one of the predominant strategies for treating ovarian cancer (OC), however, platinum resistance greatly influences the therapeutic effect. Circular RNAs (circRNAs) have been found to participate in the pathogenesis of platinum resistance. Our aim was to explore the involvement of circ_0078607 in OC cell cisplatin (DDP) resistance and its potential mechanisms.

CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription.

Epigenetic alterations have been functionally linked to ovarian cancer development and occurrence. The CXXC zinc finger protein 1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. However, its role in ovarian cancer cells is unknown.

Neddylation inhibition induces glutamine uptake and metabolism by targeting CRL3 E3 ligase in cancer cells.

Abnormal neddylation activation is frequently observed in human cancers and neddylation inhibition has been proposed as a therapy for cancer. Here, we report that MLN4924, a small-molecule inhibitor of neddylation activating enzyme, increases glutamine uptake in breast cancer cells by causing accumulation of glutamine transporter ASCT2/SLC1A5, via inactivation of CRL3-SPOP E3 ligase. We show the E3 ligase SPOP promotes ASCT2 ubiquitylation, whereas SPOP itself is auto-ubiquitylated upon glutamine deprivation.

LncRNA LINC00942 promotes chemoresistance in gastric cancer by suppressing MSI2 degradation to enhance c-Myc mRNA stability.

Background: Chemoresistance to cisplatin (DDP) remains a major challenge in advanced gastric cancer (GC) treatment. Although accumulating evidence suggests an association between dysregulation of long non-coding RNAs (lncRNAs) and chemoresistance, the regulatory functions and complexities of lncRNAs in modulating DDP-based chemotherapy in GC remain under-investigated. This study was designed to explore the critical chemoresistance-related lncRNAs in GC and identify novel therapeutic targets for patients with chemoresistant GC.

Hypoxia Stimulates SUMOylation-Dependent Stabilization of KDM5B.

Hypoxia is an important characteristic of the tumor microenvironment. Tumor cells can survive and propagate under the hypoxia stress by activating a series of adaption response. Herein, we found that lysine-specific demethylase 5B (KDM5B) was upregulated in gastric cancer (GC) under hypoxia conditions.

CK1δ stimulates ubiquitination-dependent proteasomal degradation of ATF4 to promote chemoresistance in gastric Cancer.

Chemoresistance remains a major obstacle to successful cancer therapy, especially for advanced cancers. It used to be recognised as a stable outcome resulting from genetic changes. However, recent studies showed that chemoresistance can also be unstable and reversible with the involvement of non-genetic alterations.

Sirt1 deacetylates and stabilizes p62 to promote hepato-carcinogenesis.

p62/SQSTM1 is frequently up-regulated in many cancers including hepatocellular carcinoma. Highly expressed p62 promotes hepato-carcinogenesis by activating many signaling pathways including Nrf2, mTORC1, and NFκB signaling. However, the underlying mechanism for p62 up-regulation in hepatocellular carcinoma remains largely unclear.

Neddylation regulation of mitochondrial structure and functions.

Mitochondria are the powerhouse of a cell. The structure and function of mitochondria are precisely regulated by multiple signaling pathways. Neddylation, a post-translational modification, plays a crucial role in various cellular processes including cellular metabolism via modulating the activity, function and subcellular localization of its substrates.

SLC7A11/xCT in cancer: biological functions and therapeutic implications.

Amino acid transporters mediate substrates across cellular membranes and their fine-tuned regulations are critical to cellular metabolism, growth, and death. As the functional component of system Xc-, which imports extracellular cystine with intracellular glutamate release at a ratio of 1:1, SLC7A11 has diverse functional roles in regulating many pathophysiological processes such as cellular redox homeostasis, ferroptosis, and drug resistance in cancer. Notably, accumulated evidence demonstrated that SLC7A11 is overexpressed in many types of cancers and is associated with patients' poor prognosis.

Analysis of Prognostic Factors and Design of Prognosis Model for Patients with Stage IV Gastric Cancer Following First-Line Palliative Chemotherapy.

Background: This study was to investigate the prognostic factors of patients with advanced gastric cancer and described a sample model to better differentiate the patients who could better benefit from palliative chemotherapy.

Patients And Methods: In this retrospective study, 112 gastric cancer patients at stage IV following first-line chemotherapy were enrolled from July 2013 to September 2019. The clinical factors including age, sex, ECOG, pathologic types, metastatic sites, blood indexes, response of first-line chemotherapy, and survival were collected.

β-catenin represses miR455-3p to stimulate m6A modification of HSF1 mRNA and promote its translation in colorectal cancer.

Background: Heat shock transcription factor1 (HSF1) was overexpressed to promote glutaminolysis and activate mTOR in colorectal cancer (CRC). Here, we investigated the mechanism for cancer-specific overexpression of HSF1.

Methods: HSF1 expression was analyzed by chromatin immunoprecipitation, qRT-PCR, immunohistochemistry staining and immunoblotting.

LncRNAs regulate metabolism in cancer.

Metabolic reprogramming is a hallmark of cancer. Mammalian genome is characterized by pervasive transcription, generating abundant non-coding RNAs (ncRNAs). Long non-coding RNAs (lncRNAs) are freshly discovered functional ncRNAs exerting extensive regulatory impact through diverse mechanisms.

MLN4924: additional activities beyond neddylation inhibition.

MLN4924, a small molecular inhibitor of NEDD8 (neuronal precursor cell-expressed developmentally downregulated protein 8) activating enzyme (NAE), blocks cullin neddylation to inactivate cullin-RING ligase. We found that MLN4924 has additional activities: it triggers EGFR dimerization and activation of RAS/MAPK and PI3K/AKT1 signals to stimulate tumor sphere formation and inhibit ciliogenesis; and it triggers PKM2 tetramerization to promote glycolysis.

Metabolic enzyme PDK3 forms a positive feedback loop with transcription factor HSF1 to drive chemoresistance.

: Dysregulation of metabolism plays an important role in the development and progression of cancers, while the underlying mechanisms remain largely unknown. This study aims to explore the regulation and relevance of glycolysis in chemoresistance of gastric cancer. Biochemical differences between chemoresistant and chemosensitive cancer cells were determined by metabolism profiling, microarray gene expression, PCR or western blotting.

SIRT1 deacetylated and stabilized XRCC1 to promote chemoresistance in lung cancer.

Chemoresistance is one of the most important challenges in the clinical management of lung cancer. SIRT1 is a NAD dependent protein deacetylase and implicated in diverse cellular processes such as DNA damage repair, and cancer progression. SIRT1 is upregulated in chemoresistant lung cancer cells, genetic knockdown or chemical inhibition of SIRT1 reversed chemoresistance by enhancing DNA damage and apoptosis activation, accompanied with XRCC1 degradation.