Cellular Signalling

BACKGROUND: Osteoarthritis (OA) is a prevalent ailment characterized by the gradual degradation of joints, resulting in discomfort and restricted movement. The recently proposed mechanism of ferroptosis is intricately associated with the initiation and progression of OA. Our study found that the long non-coding RNA HOXA11-AS reduces ferroptosis by increasing the expression of SLC3A2 through the transcription factor POU2F2. MATERIALS AND METHODS: HOXA11-AS was identified through lncRNA microarray analysis, and its impact on chondrocytes and extracellular matrix was assessed using real-time quantitative PCR, western blotting, and CCK8 assays...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19). Severe and fatal COVID-19 cases often display cytokine storm i.e. significant elevation of pro-inflammatory cytokines and acute respiratory distress syndrome (ARDS) with systemic hypoxia. Understanding the mechanisms of these pathogenic manifestations would be essential for the prevention and especially treatment of COVID-19 patients. Here, using a dual luciferase reporter assay for hypoxia-response element (HRE), we initially identified SARS-CoV-2 nonstructural protein 5 (NSP5), NSP16, and open reading frame 3a (ORF3a) to upregulate hypoxia-inducible factor-1α (HIF-1α) signaling...

Mammalian cardiomyocytes become terminally-differentiated during the perinatal period. In rodents, cytokinesis ceases after a final division cycle immediately after birth. Nuclear division continues and most cardiomyocytes become binucleated by ~11 days. Subsequent growth results from an increase in cardiomyocyte size. The mechanisms involved remain under investigation. Mitogen-activated protein kinases (MAPKs) regulate cell growth/death: extracellular signal-regulated kinases 1/2 (ERK1/2) promote proliferation, whilst c-Jun N-terminal kinases (JNKs) and p38-MAPKs respond to cellular stresses...

Cisplatin, a platinum-based anticancer drug, is used to treat several types of cancer. Despite its effectiveness, cisplatin-induced side effects have often been reported. Although cisplatin-induced toxicities, such as apoptosis and/or necrosis, have been well studied, the fate of cells after exposure to sublethal doses of cisplatin needs further elucidation. Treatment with a sublethal dose of cisplatin-induced cell cycle arrest at the G2 phase in retinal pigment epithelial cells. Following cisplatin withdrawal, the cells irreversibly exit the cell cycle and become senescent...

Cellular death evasion is a defining characteristic of human malignancies and a significant contributor to therapeutic inefficacy. As a result of oncogenic inhibition of cell death mechanisms, established therapeutic regimens seems to be ineffective. Mitochondria serve as the cellular powerhouses, but they also function as repositories of self-destructive weaponry. Changes in the structure and activities of mitochondria have been consistently documented in cancer cells. In recent years, there has been an increasing focus on using mitochondria as a targeted approach for treating cancer...

Oxidative stress causes damage to cancer cells and plays an important role in cancer therapy. Antagonizing oxidative stress is crucial for cancer cells to survive during the oxidation-based therapy. In this study, we defined the role of nuclear receptor co-activator 7 (NCOA7) in anti-oxidation in lung cancer cells and found that NCOA7 protects lung cancer A549 cells from the oxidative damage caused by hydrogen peroxide. Knockdown of NCOA7 in A549 cells significantly enhanced the hydrogen peroxide-caused inhibition of cell proliferation and migration, and markedly increased the damage effect of hydrogen peroxide on F-actin and focal adhesion structure, suggesting that NCOA7 protects F-actin and focal adhesion structure, thus the cell proliferation and migration, from oxidation-caused damage...

This study aimed to investigate the effects of hepatic microRNA-122 (miR-122) on Sortilin-mediated apolipoprotein B100 (apoB-100) secretion, and on aortic lipid deposition and atherosclerosis (AS) lesions and to clarify the antiatherosclerotic mechanism of 6-methylcoumarin (6-MC) via the modulation of miR-122. Bioinformatics analysis revealed that miR-122 was putatively overexpressed in a liver-specific manner and was downregulated in steatotic livers. miR-122 was shown to suppress the expression of Sortilin by complementarily pairing to the 3'-untranslated region (3'-UTR) of Sortilin mRNA via bioinformatics and dual-luciferase reporter assays, impeding Sortilin-mediated apoB-100 secretion from HepG2 cells...

Pancreatic cancer (PC) is highly malignancy with poor survival. Ferroptosis offers a novel therapeutic target for cancer treatment and glutathione peroxidase 4 (GPX4) shields tumor cells from ferroptosis damage. Although Sterol regulatory element-binding protein 1 (SREBP1) has been implicated in the development of pancreatic cancer, its underlying mechanisms remain unclear. This research aims to explore the role of SREBP1 in ferroptosis by using its inhibitor Fatostatin. In this study, Fatostatin was found to inhibit the proliferation and clonogenicity of pancreatic cancer cell lines...

BACKGROUND: High expression of low-density lipoprotein receptor related protein 11 (LRP11) has been associated with unfavorable prognosis of breast cancer (BC). This study explores the exact roles of LRP11 in BC progression and investigates the associated mechanism. METHODS: LRP11 expression in BC tissues and cells was determined by immunohistochemistry or RT-qPCR. LRP11 upregulation was induced in two human BC cell lines to investigate its impact on cell proliferation, migration, and invasion...

Histone deacetylase 5 (HDAC5) is an enzyme that deacetylates lysine residues on the N-terminal of histones and other proteins. It has been reported that HDAC5 deacetylates p53, the critical factor regulating cell cycle, in response to cellular stress, but the transcriptional products haven't been identified. Herein, we used p53 signaling pathway qPCR-chip to determine how HDAC5-mediated deacetylation of p53 affects cell cycle. However, validation using immunoblotting analysis revealed that acetylation of p53 at K120 impacted little to the expression of the genes identified using the qPCR-chip, indicating HDAC5 might deacetylate some other proteins to facilitate cell cycle via transactivating the differentially expressed genes determined by the qPCR-chip...

Crosstalk between cancer-associated fibroblasts (CAFs) and tumour cells plays a critical role in multiple cancers, including hepatocellular carcinoma (HCC). CAFs contribute to tumorigenesis by secreting growth factors, modifying the extracellular matrix, supporting angiogenesis, and suppressing antitumor immune responses. However, effect and mechanism of CAF-mediated promotion of hepatocellular carcinoma cells are still unclear. In study, we demonstrated CAFs promoted the proliferation and inhibited the apoptosis of HCC cells by secreting interleukin-6 (IL-6), which induced autocrine insulin-like growth factor-1 (IGF-1) in HCC...

While certain members of ubiquitin-coupled enzymes (E2s) have garnered attention as potential therapeutic targets across diverse diseases, research progress on Ubiquitin-Conjugating Enzyme 5 (UBC5)-a pivotal member of the E2s family involved in crucial cellular processes such as apoptosis, DNA repair, and signal transduction-has been relatively sluggish. Previous findings suggest that UBC5 plays a vital role in the ubiquitination of various target proteins implicated in diseases and homeostasis, particularly in various cancer types...

Gliomas, the most prevalent malignant brain tumors in the central nervous system, are marked by rapid growth, high recurrence rates, and poor prognosis. Glioblastoma (GBM) stands out as the most aggressive subtype, characterized by significant heterogeneity. The etiology of gliomas remains elusive. RNA modifications, particularly reversible methylation, play a crucial role in regulating transcription and translation throughout the RNA lifecycle. Increasing evidence highlights the prevalence of RNA methylation in primary central nervous system malignancies, underscoring its pivotal role in glioma pathogenesis...

BACKGROUND AND AIMS: Acetaminophen (APAP) is the main cause of acute liver injury (ALI) in the Western. Our previous study has shown that fenofibrate activated hepatic expression of fibroblast growth factor 21 (FGF21) can protect the liver form APAP injuries by promoting autophagy. However, the underlying mechanism involved in FGF21-mediated autophagy remains unsolved. METHODS: The ALI mice model was established by intraperitoneal injection of APAP. To investigate the influence of FGF21 on autophagy and Sirt1 expression in APAP-induced ALI, FGF21 knockout (FGF21KO) mice and exogenously supplemented mouse recombinant FGF21 protein were used...

BACKGROUND: Nitric oxide and Reactive Nitrogen Species are known to effect tumorigenicity. GSNO is one of the main NO carrying signalling moiety in cell. In the current study, we tried to delve into the effect of GSNO induced nitrosative stress in three different myelogenous leukemic K562, U937 and THP-1 cell lines. METHOD: WST-8 assay was performed to investigate cell viability. RT-PCR and western-blot analysis were done to investigate mRNA and protein expression...

Cancer remains a leading cause of morbidity and mortality worldwide, necessitating the ongoing investigation of molecular targets for improved diagnosis, prognosis, and therapy. Among these targets, RNA modifications, particularly N5-methylcytosine (m5C) in RNA, have emerged as critical regulators of gene expression and cellular functions. NOP2/Sun RNA methyltransferase family member 2 (NSUN2) is a key enzyme in m5C modification, significantly influencing various biological processes and tumorigenesis. NSUN2 methylates multiple RNA species, including transfer RNAs (tRNAs), messenger RNAs (mRNAs), and non-coding RNAs, impacting RNA stability, translation efficiency, and cellular stress responses...

Sepsis is a systemic inflammatory disease that can cause multiple organ damage. Septic patients with cardiac dysfunction have a significantly higher mortality. Based on the results of bioinformatics analysis, weighted gene co-expression network analysis (WGCNA), we found that Erbin is vital in cardiomyocyte. However, the function of Erbin in sepsis-induced cardiomyopathy (SIC) has not been explicitly studied. We discussed the role of Erbin in SIC by employing the Erbin-/- mice and HL-1 cardiomyocyte. An in vitro model of inflammation in HL-1 was used to confirm stimulation with lipopolysaccharide (LPS) and a mouse model of cecal ligation and puncture (CLP) to study the molecular under SIC...

Acute myocardial infarction (AMI) is the leading cause of death worldwide, and reperfusion therapy is a critical therapeutic approach to reduce myocardial ischemic injury and minimize infarct size. However, ischemia/reperfusion (I/R) itself also causes myocardial injury, and inflammation is an essential mechanism by which it leads to myocardial injury, with macrophages as crucial immune cells in this process. Macrophages are innate immune cells that maintain tissue homeostasis, host defence during pathogen infection, and repair during tissue injury...

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BACKGROUND: Transforming growth factor-beta1 (TGF-β1)-mediated renal fibrosis is a critical pathological process of chronic kidney disease worsening to end-stage renal disease. Recent studies have shown that long noncoding RNA H19 (lncRNA H19) is widely involved in the formation and progression of fibrosis in multiple organs. However, its molecular events in renal fibrosis remain to be elucidated. METHODS: Rats were treated with adenine intragastrically and HK-2 cells were induced by TGF-β1 to construct renal fibrosis models in vivo and in vitro, respectively...