Whole-gene CRISPR/cas9 library screen revealed targeting STAT6 increased the sensitivity of liver cancer to celecoxib via inhibiting arachidonic acid shunting.

Celecoxib, a selective COX-2 inhibitor, has demonstrated anti-liver cancer effects in various preclinical models and clinical traits. However, prolonged use of celecoxib can lead to drug resistance, necessitating higher doses to maintain efficacy, which often results in severe side effects, limiting its clinical application. This study aimed to identify strategies to overcome celecoxib resistance in liver cancer.

MRO/HNRNPU/CCL5 feedback loop amplifies M2 macrophage and breast cancer cell crosstalk to drive progression.

Background: M2 macrophages are known to enhance the malignant phenotype of breast cancer (BC) cells, yet the underlying mechanisms remain unclear.

Methods: scRNA sequencing analysis, chromatin immunoprecipitation, immunoprecipitation, exosome isolation, and biological experiments were used to analyze this crosstalk.

Results: Maestro (MRO) was involved in the crosstalk between M2 macrophages and BC cells.

I-labelled BMSC-Derived Extracellular Vesicles Deliver CRISPR/Cas9 Ribonucleoproteins With a GFP-Reporter System to Inhibit Osteosarcoma Proliferation and Metastasis.

Metastasis constitutes the principal factor leading to the unfavourable prognosis of osteosarcoma patients. Hypoxia, as the inherent microenvironment of osteosarcoma, can upregulate HIF-1α via multiple pathways, thereby facilitating osteosarcoma proliferation and metastasis. Our previous research indicated that the inwardly rectifying potassium channel subfamily J member 2 (KCNJ2) inhibits the degradation of HIF-1α in osteosarcoma.

In vivo CRISPR screening identifies POU3F3 as a novel regulator of ferroptosis resistance in hepatocellular carcinoma via retinoic acid signaling.

Background: Sorafenib, a ferroptosis agonist, is a first-line treatment for advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is limited due to drug resistance, resulting in modest improvements in patient survival. Hence, the present study has been designed to identify critical molecular targets associated with sorafenib resistance and investigate the potential inhibitors in overcoming this therapeutic challenge.

aGenome-scale activation screen reveals lncRNA HNF1A-AS1 promotes pancreatic cancer metastasis through interacting with U2SURP to increase CD44 alternative splicing.

Background: Pancreatic cancer (PC) has a strong ability to invade and metastasize, which has brought insurmountable obstacles to the treatment of PC. Exploring the molecular mechanism of PC metastasis is still the focus of PC research. The purpose of this study was to explore the molecular mechanism of long noncoding RNA HNF1A-AS1 in promoting PC metastasis, hoping to provide help for the diagnosis and treatment of PC.

Targeting INF2 with DiosMetin 7-O-β-D-Glucuronide: a new stratagem for colorectal cancer therapy.

Background And Purpose: Colorectal cancer (CRC) is the third most prevalent malignancy in the gastrointestinal tract and the second leading cause of cancer-related deaths. Despite the identification of numerous biomarkers, their non-specific distribution across different cell types complicates the development of targeted therapies. Therefore, this study aims to identify specific biomarkers for CRC and utilize them for the development of targeted therapies.

Cyclization of archaeal membrane lipids impacts membrane protein activity and archaellum formation.

Enhancement of the cyclization of membrane lipids GDGTs (glycerol dialkyl glycerol tetraethers) is a critical strategy for archaea to adapt to various environmental stresses. However, the physiological function of membrane lipid cyclization remains unclear. Here, we reported that the GDGT ring synthases mutant, deficient in GDGT cyclization, inhibited archaellum formation and reduced cell motility in thermoacidophilic crenarchaeon .

Engineering archaeal membrane-spanning lipid GDGT biosynthesis in bacteria: Implications for early life membrane transformations.

Eukaryotes are hypothesized to be archaeal-bacterial chimeras. Given the different chemical structures of membrane phospholipids in archaea and bacteria, transformations of membranes during eukaryogenesis that led to the bacterial-type membranes of eukaryotic cells remain a major conundrum. One of the possible intermediates of eukaryogenesis could involve an archaeal-bacterial hybrid membrane.

Identification of the clinical value and biological effects of TTN mutation in liver cancer.

Liver cancer, a malignant tumor of the digestive system, is a leading cause of cancer‑related mortality globally. Numerous genetic mutations associated with tumorigenesis have been identified, stemming from genomic instability. However, the clinical implications and therapeutic relevance of these mutations remain poorly understood.

Using weighted gene co-expression network analysis to identify key genes related to preeclampsia.

Introduction: The pathogenesis of preeclampsia remains unclear, highlighting the need for the creation of dependable biomarkers. This study aimed to pinpoint genetic risk factors linked to preeclampsia through the utilization of weighted gene co-expression network analysis (WGCNA).

Methods: A gene expression profile dataset from the placentas of patients with preeclampsia was acquired from the Gene Expression Omnibus (GEO) database and employed as a discovery cohort to construct a WGCNA network.

Bioinformatics Combined With Biological Experiments to Identify the Pathogenetic Link of Type 2 Diabetes for Breast Cancer.

Background: Type 2 diabetes mellitus (T2DM) constitutes a significant risk factor for breast cancer (BC), with affected women exhibiting a two- to three-fold increased likelihood of developing BC. Furthermore, women diagnosed with both BC and T2DM tend to experience poorer prognoses and exhibit greater resistance to various treatments compared to their non-diabetic counterparts. Consequently, elucidating the comorbidities associated with T2DM and BC is instrumental in enhancing the diagnostic and therapeutic strategies for BC.

Terpinen-4-ol suppresses proliferation and motility of cutaneous squamous cell carcinoma cells by enhancing calpain-2 expression.

Background: Terpinen-4-ol (T4O), a key constituent of tea tree essential oil and various aromatic plants, has shown promising antiproliferative and pro-apoptotic effects in melanoma and other cancer types. However, its efficacy against cutaneous squamous cell carcinoma (cSCC) remains unclear. Thus, in this study, we investigated the and effects of T4O on cSCC cell lines and preliminarily explored its impacting pathways.

CXCL8 modulates M0 macrophage proliferation and polarization to influence tumor progression in cervical cancer.

Cervical cancer (CESC) presents significant clinical challenges due to its complex tumor microenvironment (TME) and varied treatment responses. This study identified undifferentiated M0 macrophages as high-risk immune cells critically involved in CESC progression. Co-culture experiments further demonstrated that M0 macrophages significantly promoted HeLa cell proliferation, migration, and invasion, underscoring their pivotal role in modulating tumor cell behavior within the TME.

Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of glioma.

Cytokines, tumor cells, and tumor-associated macrophages play crucial roles in the composition of glioma tissue. Studies have demonstrated that certain cytokines can induce M2 polarization of tumor-associated macrophages and contribute to the progression of glioma. Nonetheless, the intricate molecular interactions among cytokines, glioma cells, and tumor-associated macrophages remain largely unexplored.

TMOD3 accelerated resistance to immunotherapy in KRAS-mutated pancreatic cancer through promoting autophagy-dependent degradation of ASCL4.

The high prevalence of KRAS mutations in pancreatic cancer (PC) is widely acknowledged and results in the resistance of targeted ferroptosis therapy and immunotherapy. Herein, via a CRISPR/Cas9 library screen, the effects of ferroptosis agonists were increased in KRAS-mutant PC cells upon knockout of tropomodulin 3 (TMOD3), while these effects were not observed in KRAS-wild-type cells. Increased levels of TMOD3 were found in PC tissues, particularly in those with KRAS mutations.

Identification of Clinical Value and Biological Effects of Mutation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant digestive tumor. Numerous genetic mutations have been documented in HCC, yet the clinical significance of these mutations remains largely unexplored. The objective of this study is to ascertain the clinical value and biological effects of xin actin binding repeat containing 2 () mutation in HCC.

Biosynthesis of GMGT lipids by a radical SAM enzyme associated with anaerobic archaea and oxygen-deficient environments.

Archaea possess characteristic membrane-spanning lipids that are thought to contribute to the adaptation to extreme environments. However, the biosynthesis of these lipids is poorly understood. Here, we identify a radical S-adenosyl-L-methionine (SAM) enzyme that synthesizes glycerol monoalkyl glycerol tetraethers (GMGTs).

MATN4 as a target gene of HIF-1α promotes the proliferation and metastasis of osteosarcoma.

Background: Osteosarcoma is a highly malignant bone tumor that exhibits rapid growth and early metastasis. Hypoxia plays a pivotal role in promoting the proliferation and metastasis of osteosarcoma through a series of molecular events, which are partially mediated and regulated by HIF-1α. However, the regulatory network associated with HIF-1α in osteosarcoma remains limited.

Astrocyte-specific activation of sigma-1 receptors in mPFC mediates the faster onset antidepressant effect by inhibiting NF-κB-induced neuroinflammation.

Major depressive disorder (MDD) is a global health burden characterized by persistent low mood, deprivation of pleasure, recurrent thoughts of death, and physical and cognitive deficits. The current understanding of the pathophysiology of MDD is lacking, resulting in few rapid and effective antidepressant therapies. Recent studies have pointed to the sigma-1 (σ-1) receptor as a potential rapid antidepressant target; σ-1 agonists have shown promise in a variety of preclinical depression models.

Analysis of the effects of M2 macrophage-derived PDE4C on the prognosis, metastasis and immunotherapy benefit of osteosarcoma.

Tumour-associated macrophages (TAMs), encompassing M1 and M2 subtypes, exert significant effects on osteosarcoma (OS) progression and immunosuppression. However, the impacts of TAM-derived biomarkers on the progression of OS remains limited. The GSE162454 profile was subjected to single-cell RNA (scRNA) sequencing analysis to identify crucial mediators between TAMs and OS cells.

Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM.

Background: Skin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for chemotherapy and immunotherapy response in SKCM and explore their association with oxidative stress.

Methods: Utilizing TCGA-SKCM RNA-seq data, we employed Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to identify six core genes.

mA regulator-mediated methylation modification patterns correlated with autophagy to predict the prognosis of hepatocellular carcinoma.

Background: N1-methyladenosine (mA), among the most common internal modifications on RNAs, has a crucial role to play in cancer development. The purpose of this study were systematically investigate the modification characteristics of mA in hepatocellular carcinoma (HCC) to unveil its potential as an anticancer target and to develop a model related to mA modification characteristics with biological functions. This model could predict the prognosis for patients with HCC.

HDAC6-dependent deacetylation of NGF dictates its ubiquitination and maintains primordial follicle dormancy.

Primordial follicles are limited in number and cannot be regenerated, dormant primordial follicles cannot be reversed once they enter a growth state. Therefore, the length of the female reproductive lifespan depends on the orderly progression and selective activation of primordial follicles, the mechanism of which remains unclear. We used human ovarian cortical biopsy specimens, granulosa cells from diminished ovarian reserve (DOR) patients, -overexpressing transgenic mouse model, and RNA sequencing to analyze the crucial roles of histone deacetylase 6 (HDAC6) in fertility preservation and primordial follicle activation.