SKP2 inhibition activates tumor cell-intrinsic immunity by inducing DNA replication stress and genomic instability.

Background: S-phase kinase-associated protein 2 (SKP2) is a typical oncogene aberrantly overexpressing in a variety of cancer types, but it remains elusive whether SKP2 regulates the antitumor immunity of triple-negative breast cancer.

Methods: The efficacy of anti-PD-1 was evaluated in the orthotopic xenografts of immunocompetent mice models. The infiltration of cytotoxic T cells in tumor microenvironment(TME) were assessed by immunofluorescence staining.

Risk factors and nomogram predictive models for postsurgical progression/hyperprogression recurrence in hepatocellular carcinoma with macroscopic vascular invasion.

Purpose: This study aimed to develop postsurgical progression/hyperprogression recurrence (type III-IV recurrence) prediction models for hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion (MaVI) and to guide treatment strategies in the accurate healthcare era.

Patients And Methods: 393 HCC patients with MaVI from two central hospitals made up the entire study population. In developmental (290 patients) and validation (103 patients) cohorts, all patients were randomized into one or the other.

Investigation of the causal relationship between breast cancer and thyroid cancer: a set of two-sample bidirectional Mendelian randomization study.

Purpose: A potential association between breast (BC) and thyroid cancer (TC) has been observed. We investigated if the relationship between BC and TC is causal using bidirectional Mendelian randomization (MR) in Asian and European populations.

Methods: BC-linked single nucleotide polymorphisms (SNPs) were acquired from a genome-wide association study (GWAS) conducted by the Breast Cancer Association Consortium and Biobank Japan.

New evidence: Metformin unsuitable as routine adjuvant for breast cancer: a drug-target mendelian randomization analysis.

Purpose: The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk.

Methods: Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.

Specific gut microbiome signature predicts hepatitis B virus-related hepatocellular carcinoma patients with microvascular invasion.

Background: We aimed to assess differences in intestinal microflora between patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) and those without MVI. Additionally, we investigated the potential of the microbiome as a non-invasive biomarker for patients with MVI.

Methods: We analyzed the preoperative gut microbiomes (GMs) of two groups, the MVI ( = 46) and non-MVI ( = 56) groups, using 16S ribosomal RNA gene sequencing data.

PLK1 maintains DNA methylation and cell viability by regulating phosphorylation-dependent UHRF1 protein stability.

PLK1 is a key serine/threonine kinase as well as a master mitotic regulator, but it has never been reported that PLK1 regulates DNA methylation. In the present study, we for the first time found that PLK1 inhibition disrupted global DNA methylation and elevated the expression level of tumor suppressor genes. Mechanistically, we found that PLK1 interacts UHRF1 protein to induce its phosphorylation at serine 265.

UHRF1 promotes spindle assembly and chromosome congression by catalyzing EG5 polyubiquitination.

UHRF1 is an epigenetic coordinator bridging DNA methylation and histone modifications. Additionally, UHRF1 regulates DNA replication and cell cycle, and its deletion induces G1/S or G2/M cell cycle arrest. The roles of UHRF1 in the regulation of G2/M transition remain poorly understood.

ATM-Mediated translocation of RanBPM regulates DNA damage response by stabilizing p21 in non-small cell lung cancer cells.

Purpose: Platinum-based chemotherapy remains a standard-of-care for most patients with advanced non-small cell lung cancer (NSCLC). DNA damage response (DDR) induced by platinum or Etoposide activated a panel of cell cycle-regulatory proteins including p21 through p53 pathway. Previous studies have reported that RanBPM has been involved in various cellular processes such as DDR by interacting with multiple proteins.

AR antagonists develop drug resistance through TOMM20 autophagic degradation-promoted transformation to neuroendocrine prostate cancer.

Background: Prostate cancer(PCa) is the most commonly occurring male cancer in the USA. Abiraterone or Enzalutamide have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC). However, the treatment-emergent neuroendocrine PCa (t-NEPC) may develop, resulting in drug resistance in about 10-17% CRPC patients.

Prognostic factors and an innovative nomogram model for patients with hepatocellular carcinoma treated with postoperative adjuvant transarterial chemoembolization.

Purpose: The purpose of this study was to estimate the clinical efficacy and identify the best beneficiaries of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in hepatocellular carcinoma (HCC).

Patients And Methods: A total of 749 HCC patients who underwent surgical resection (380 underwent PA-TACE, 369 had resection only) with a high risk of recurrence were reviewed retrospectively. Patients receiving PA-TACE were randomly split into development and validation cohorts.

Down-regulation of ALDOB during metabolic reprogramming mediates malignant behavior in hepatocellular carcinoma and insensitivity to postoperative adjuvant transarterial chemoembolization.

Background: Postoperative transarterial chemoembolization (PA-TACE) is an effective adjuvant therapy for preventing early postoperative recurrence of hepatocellular carcinoma (HCC); however, many patients are insensitive to it. Therefore, the present study aimed to explore the in-depth reasons for PA-TACE resistance and provide a reliable basis for selecting patients who will benefit the most from PA-TACE.

Methods: The unique gene expression profiles of primary tumors from PA-TACE-sensitive or -insensitive patients were analyzed using microarray data.

Diosgenin inhibits prostate cancer progression by inducing UHRF1 protein degradation.

Prostate cancer (PCa) represents the second cause of cancer death in adult men. Aberrant overexpression of UHRF1 has been reported in several cancer types, and is regarded as a novel drug target for cancer therapy. Nevertheless, no UHRF1-targeted small molecule inhibitor has been testing in clinical trials.

AKT1 regulates UHRF1 protein stability and promotes the resistance to abiraterone in prostate cancer.

Oncogenic activation of PI3K/AKT signaling pathway, together with epigenetic aberrations are the characters of castration-resistant prostate cancer (CRPC). UHRF1 as a key epigenetic regulator, plays a critical role in prostate cancer (PCa) development, and its expression is positively correlated with the degree of malignancy. In this present study we investigated the potential regulatory mechanism of AKT1 on UHRF1, and further validated the in vitro and in vivo anticancer efficacy of AKT phosphorylation inhibitor MK2206 in combination with abiraterone.

Clinical implications and biological features of a novel postoperative recurrent HCC classification: A multi-centre study.

Background & Aims: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine.

Methods: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178).

Gut microbiome dysbiosis in patients with hepatitis B virus-related hepatocellular carcinoma after extended hepatectomy liver failure.

Background: Hepatitis B virus-related hepatocellular carcinoma (B-HCC) negatively affects the gut microbiome. This study aimed to investigate the gut microbiome profiles and functions post-hepatectomy liver failure (PHLF) after extended hepatectomy (e-PHLF) to obtain valuable insights, identify potential diagnostic biomarkers, and assist in the treatment of this disease.

Methods: B-HCC patients who underwent extended hepatectomy were consecutively recruited and divided into Group A (n=15) and Group B (n=15) based on the presence and absence of e-PHLF, respectively.

Norcantharidin promotes cancer radiosensitization through Cullin1 neddylation-mediated CDC6 protein degradation.

Radiotherapy (RT) is a conventional cancer therapeutic modality. However, cancer cells tend to develop radioresistance after a period of treatment. Diagnostic markers and therapeutic targets for radiosensitivity are severely lacking.

Operable hepatitis B virus-related hepatocellular carcinoma: gut microbiota profile of patients at different ages.

Background: Age was important prognostic factors for operable hepatocellular carcinoma patients. The aim of the present study was to assess the difference in gut microbiota in patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) at different ages ; to investigate the features of the microbiota and its function associated with different ages; to provide a preliminary look at effects of the gut microbiota dimension on prognostic.

Methods: From September 2020 to May 2021, patients with HBV-HCC were able to undergo liver resection and were recruited consecutively and divided into the younger age group (age <45 years) (Y.

Liver resection for large and huge hepatocellular carcinoma: Predictors of failure, recurrence patterns, and prognoses.

Background: Characteristic symptoms and signs are often absent in patients with hepatocellular carcinoma (HCC). As a result, many patients are not diagnosed until their tumors have grown to large (> 5cm) or huge sizes (> 10cm). Liver resection has traditionally been reserved for patients with small HCC, but more recently it is being used for patients with large and huge tumors.

Integrated omics analysis: the relationship between significantly increased post-hepatectomy and decreased hub-metabolite 3-methyl-2-oxobutanoic acid is associated with induced liver failure.

Background: This study sought to evaluate the association between intestinal and post-hepatectomy liver failure (PHLF) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (B-HCC), and identify the inner relationship.

Methods: Patients with B-HCC were divided into Groups A and B based on the presence or absence of PHLF. 16S ribosomal ribonucleic acid surveys were used to identify gut microbiome alterations.

Outcomes of postoperative adjuvant transarterial chemoembolization for hepatocellular carcinoma according to the Ki67 index.

To assess whether Ki67 is related to the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in hepatocellular carcinoma patients at high risk of postsurgical recurrence. A total of 716 patients undergoing surgical resection with or without PA-TACE were retrospectively enrolled. Immunohistochemistry was used to analyze Ki67 expression.

Histone methyltransferase WHSC1 loss dampens MHC-I antigen presentation pathway to impair IFN-γ-stimulated antitumor immunity.

IFN-γ-stimulated MHC class I (MHC-I) antigen presentation underlies the core of antitumor immunity. However, sustained IFN-γ signaling also enhances the programmed death ligand 1 (PD-L1) checkpoint pathway to dampen antitumor immunity. It remains unclear how these opposing effects of IFN-γ are regulated.

UHRF1 promotes androgen receptor-regulated CDC6 transcription and anti-androgen receptor drug resistance in prostate cancer through KDM4C-Mediated chromatin modifications.

The UHRF1 and CDC6, oncogenes play critical roles in therapeutic resistance. In the present study, we found that UHRF1 mediates androgen receptor (AR)-regulated CDC6 transcription in prostate cancer cells. In prostate cancer tissues and cell lines, levels of UHRF1 and CDC6 were simultaneously upregulated, and this was associated with worse survival.

The potential mechanism of miR-130b on promotion of the invasion and metastasis of hepatocellular carcinoma by inhibiting Notch-Dll1.

This study aimed to elucidate the regulatory role and molecular regulation mechanism of miR-130b gene in the process of invasion and metastasis of hepatocarcinoma, and provide a theoretical basis for seeking of effective prevention and treatment of new targets for hepatocellular carcinoma. The expression level of miR-130b gene in hepatocarcinoma tissues was determined by qRT-PCR. The biological function and mechanism of miR-130b gene were verified by cell and animal models, and the target gene was verified by double luciferase assay.

USP7 is a novel Deubiquitinase sustaining PLK1 protein stability and regulating chromosome alignment in mitosis.

Background: The deubiquitinase USP7 has been identified as an oncogene with key roles in tumorigenesis and therapeutic resistance for a series of cancer types. Recently small molecular inhibitors have been developed to target USP7. However, the anticancer mechanism of USP7 inhibitors is still elusive.