Activation of STAT3 via Y705-phosphorylation is well documented across multiple cancer types and thus forms the basis of canonical pathway to judge STAT3 activation. Recently, important roles of two other post-translational modification (PTM) sites, i.e. S727-phosphorylation and K685-acetylation, leading to STAT3 activation are reported. However, their critical mode of function in controlling STAT3

Objectives Congenital cystic adenomatoid malformation (CCAM) is the most common congenital pulmonary anomaly with unknown etiology. Here, single-cell RNA sequencing (scRNA-seq) was used to map its cellular landscape and identify the underlying cellular and molecular events related to CCAM. Methods This study involved a 4.25 year old patient with grade Ⅱ–Ⅲ CCAM at the Children's Hospital of Fudan University

The nod-like receptor protein-3 (NLRP3)-mediated pyroptosis is involved in kidney diseases. Thioredoxin interacting protein (TXNIP) directly interacts with NLRP3. This study aimed to probe the mechanism of TXNIP and NLRP3 pathway in diabetic nephropathy (DN). Marker detection and histological staining indicated that in DN rats, the renal function was destroyed, and the TXNIP/NLRP3 axis was activated

Mutations in the Lmod3 gene have been identified as a genetic cause of nemaline myopathy. However, the mechanism underlying this disease and the function of Lmod3 remain largely unknown. In this study, we found that Lmod3 knockdown in C2C12 cells impaired myoblast differentiation, whereas enforced Lmod3 expression enhanced such differentiation. We also discovered that myoblast proliferation was promoted

Colorectal cancer (CRC) is one of the most commonly diagnosed tumors among human worldwide. Angiogenesis and tumor-associated macrophage (TAM) recruitment are closely associated with CRC development. Nevertheless, the mechanisms revealing CRC progression are still not fully understood. 5′-Nucleotidase domain containing 2 (NT5DC2), a member of the NT5DC family, modulates various cellular events to mediate

Metazoan development relies on intricate cell differentiation, communication, and migration pathways, which ensure proper formation of specialized cell types, tissues, and organs. These pathways are crucially controlled by ubiquitylation, a reversible post-translational modification that regulates the stability, activity, localization, or interaction landscape of substrate proteins. Specificity of

Idiopathic pulmonary fibrosis (IPF) is a fatal fibrosing interstitial lung disease with limited therapeutic options and a median survival of 3 years after diagnosis. Dysregulated epithelial regeneration is key event involved in initiating and sustaining IPF. The type II alveolar epithelial cells (AECIIs) play a crucial role for epithelial regeneration and stabilisation of alveoli. Loss of cell apical-basal

The aim of this short review is to comment on the advantages of injecting purified molecules into a normal living cell as a complement to the constitution of a cell-free system for analyzing the function of cell components. We emphasize here that the major difference is that, by injection, most components of a cell are maintained at their normal concentration, which is difficult, even if at all possible

Vascular calcification (VC) is a major risk factor for increasing cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS), a representative uremic toxin, is closely associated with VC in CKD patients. Matrix Gla protein (MGP) plays pivotal role in VC as a calcification inhibitor. The aim of this work was to explore whether MGP was involved in IS-induced

Abnormal pattern recognition receptor (PRR) signaling plays an important role in gastric mucosal damage caused by stomach microbiota; however, the underlying molecular mechanisms remain obscure. Here, we show that DC-SIGN, a surface phenotype marker of dendritic cells, is overexpressed in gastric epithelial cells facing LPS stimulation. NLRP3 expression in gastric epithelial cells are significantly

Lesion healing without treatment is a unique clinical characteristic of the early stages of syphilis infection. Angiogenesis, which involves endothelial cell migration, is an important process in wound healing. Tp0136, an outer membrane protein of T. pallidum, has the ability to bind host fibronectin-producing cells, which plays a crucial role in the pathogenesis of syphilis. In this research, we purposed

In the present study, we have explored the prognostic value of the Phosphofructokinase Platelet-type (PFKP) expression and its therapeutic relevance in metastatic breast cancer. PFKP immunohistochemistry was performed on Invasive ductal carcinomas (IDCs; n = 87) of breast, and its association with clinicopathological parameters were evaluated. Using online meta-analysis tools, PFKP's prognostic value

Promoter region of the telomerase reverse transcriptase gene (TERTp) constitutes a regulatory element capable to affect TERT expression (TE), telomerase activity (TA) and telomere length (TL). TERTp mutation status, TL, TA and TE were assessed in 27 in vitro cultured human cell lines, including 11 solid tumour, 13 haematological and 3 normal cell lines. C228T and C250T TERTp mutations were detected

Long non-coding RNA (lncRNA) ANRIL has been reported to be closely related to the relapse of multiple myeloma patients. However, the functional role and underlying mechanism of lncRNA ANRIL in multiple myeloma are not known. This study aims to investigate the biological function of lncRNA ANRIL in multiple myeloma. In this study, compared with normal tissues from healthy donors, lncRNA ANRIL and HIF-1α

Background Polycomb group (PcG) proteins are histone modifiers which control gene expression by assembling into large repressive complexes termed - Polycomb repressive complex (PRC); RING1B, core catalytic subunit of PRC1 that performs H2AK119 monoubiquitination leading to gene repression. The role of PRC1 complex during early neural specification in humans is unclear; we have tried to uncover the

PD1/PDL1 pathway plays a critical role in cancer immune responses. The immune checkpoint inhibitors of PD1/PDL1 have been well explored and developed for immunotherapies of solid tumors. Recently, various monoclonal antibodies targeting the PD1/PDL1 pathway have emerged and achieved remarkable success in clinical trials. However, challenges with these monoclonal antibodies have appeared during cancer

Accumulating evidence shows the involvement of long non-coding RNAs (lncRNAs) in tumorigenesis of many types of human cancers. However, the role of LINC00858 in colon cancer has not been fully elucidated. Therefore, we investigated the involvement of LINC00858 in the progression of colon cancer and identified its downstream targets. After examining the expression of LINC00858 in colon cancer tissues

Chronic oxidative stress resulting from hyperlipidemia is thought to be a key pathogenic driver of pancreatic β-cell dysfunction in leading to the onset of type 2 diabetes mellitus (T2DM). Long non-coding RNAs (lncRNAs) have been increasingly recognized to regulate dysfunction within pancreatic β-cells in the context of T2DM. In the present study, we sought to comprehensively analyze the roles of lncRNAs

Purpose Recent findings have shown that circRNA dysregulation was involved in the development of many types of cancer. However, our knowledge of circRNA in oral squamous cell carcinoma (OSCC) remains elusive. Methods Here, we explored whether ciRS-7 could function as a ceRNA in promoting metastasis of OSCC via regulating miR-7 activity. The expression levels of ciRS-7 and miR-7 were examined in clinical

Mechanobiological responses by osteoblasts are governed by downstream Rho-ROCK signalling through actin cytoskeleton re-arrangements but whether these responses are influenced by estrogen deficiency during osteoporosis remains unknown. The objective of this study was to determine alterations in the mechanobiological responses of estrogen-deficient osteoblasts and investigate whether an inhibitor of

Recently, increasing evidences indicated that Platycodin D (PD) served as an effective anti-tumor drug for cancer treatment in clinic. However, the molecular mechanisms are still unclear. In the present study, we proved that PD regulated LncRNA-XIST/miR-335 axis to hamper the development of bladder cancer in vitro and in vivo. Mechanistically, PD inhibited malignant phenotypes, including cell proliferation

Human papillomavirus (HPV) infection and viral protein expression cause several epigenetic alterations that lead to cervical carcinogenesis. Our previous study identified that upregulated lysine-specific demethylase (KDM) 2 A promotes cervical cancer progression by inhibiting mircoRNA (miR)-132 function. However, the roles of histone methylation modifiers in HPV-related cervical cancer remain unclear

Cancer stem cells (CSCs) play an important role in shaping the invasive cancer phenotype by contributing to tumor initiation, metastasis, relapse, and therapeutic resistance in non-small cell lung cancer (NSCLC). The Aryl hydrocarbon receptor (AhR), a ligand activated transcription factor, which is well known for mediating the toxicity and tumorigenesis of a variety of environmental pollutants, has

Myst family genes encode lysine acetyltransferases that mainly mediate histone acetylation to control transcription, DNA replication and DNA damage response. They form tetrameric complexes with PHD-finger proteins (Brpfs or Jades) and small non-catalytic subunits Ing4/5 and Meaf6. Although all the components of the complex are well-conserved from yeast to mammals, the function of Meaf6 and its homologs

Purpose Emerging evidence has suggested the functions of exosomes in allergic diseases including asthma. This work aimed to study the roles of M2 macrophage-derived exosomes (M2Φ-Exos) in pediatric asthma progression and the potential molecules. Methods A mouse model with asthma was induced by ovalbumin (OVA) and treated with M2Φ-Exos. The secretion of inflammatory cytokines, fibrosis and inflammatory

Osteosarcoma (OS) is a bone malignancy affecting children and adolescents. Retinoblastoma (RB) patients with germline RB1 mutations are susceptible to osteosarcoma in the second decade of their life. Several studies, particularly in mice, have revealed a role for RB1 in osteogenesis. Since, there is species specific difference attributed in retinoblastoma tumorigenesis between mice and human, we assumed

High expression of the immune checkpoint receptor PD-L1 is associated with worse patient outcome in a variety of human cancers, including head and neck squamous cell carcinoma (HNSCC). Binding of PD-L1 with its partner PD-1 generates an inhibitory signal that dampens the immune system. Immunotherapy, that is blocking the PD-1/PD-L1 checkpoint, has proven to be an effective tool in cancer therapy. However

Many bone diseases result from abnormal bone resorption by osteoclasts (OCs). Studying OC related regulatory genes is necessary for the development of new therapeutic strategies. Rho GTPases have been proven to regulate OC differentiation and function and only mature OCs can carry out bone resorption. Here we demonstrate that Rac1 and Cdc42 exchange factor Triple functional domain (Trio) is critical

Autophagy is an evolutionary conserved catabolic process devoted to the removal of unnecessary and harmful cellular components. In its general form, autophagy governs cellular lifecycle through the formation of double membrane vesicles, termed autophagosomes, that enwrap and deliver unwanted intracellular components to lysosomes. In addition to this omniscient role, forms of selective autophagy, relying

Glioma stem cells (GSCs) have been implicated in the promotion of malignant progression. Epidermal growth factor receptor variant (EGFRv) has been associated with glioma “stemness”. However, the molecular mechanism is not clear. In this study, we were committed to investigate the role of EGFRv in GSCs and presented a new therapeutic target in EGFRvIII positive GSCs. The results showed that EGFRvIII

CD8+ T cells are considered a critical component of antitumor immunity. However, tumor-infiltrating CD8+ T cells may express more than one checkpoint molecules that have the potential to inhibit effector responses alone or cooperatively. Here, we focused on the expression dynamic of TIGIT and PD-1 in CD8+ T cells. TIGIT+ subset presented significantly higher PD-1 expression than TIGIT− subset in circulating

Epigenetic modifications allow cells to quickly alter their gene expression and adapt to different stresses. In addition to direct chromatin modifications, prion-like proteins have recently emerged as a system that can sense and adapt the cellular response to stressful conditions. Interestingly, such responses are maintained through prions' self-templating conformations and transmitted to the progeny

A hallmark of aging is the progressive accumulation of cellular damage. Age-induced damage arises due to a decrease in organelle function along with a decline in protein quality control. Although somatic tissues deteriorate with age, the germline must maintain cellular homeostasis in order to ensure the production of healthy progeny. While germline quality control has been primarily studied in multicellular

The aggregation of β-amyloid (Aβ) peptide in Alzheimer's disease (AD) is characterized by mitochondrial dysfunction and mitophagy impairment. Mitophagy is a homeostatic mechanism by which autophagy selectively eliminates damaged mitochondria. Valinomycin is a respiratory chain inhibitor that activates mitophagy via the PINK1/Parkin signaling pathway. However, the mechanism underlying the association

Cellular uptake of vitamin B12 (cobalamin, Cbl) is mediated by a cell surface receptor (TCblR/CD320) that binds transcobalamin (TC) saturated with Cbl. TC is secreted by the vascular endothelium, has a relatively short half-life, binds Cbl with high affinity and presents the vitamin to the receptor for cellular uptake. Here we show binding and internalization of the TC-Cbl complex along with its’ receptor

Background Apoptin can specifically kill cancer cells but has no toxicity to normal cells. Human telomerase reverse transcriptase (hTERT) acts as a tumor-specific promoter, triggering certain genes to replicate or express only in tumor cells, conferring specific replication and killing abilities. This study aimed at investigating the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a

FAM122A is a housekeeping gene and highly conserved in mammals. More recently, we have demonstrated that FAM122A is essential for maintaining the growth of hepatocellular carcinoma cells, in which we unexpectedly found that FAM122A deletion increases γH2AX protein level, suggesting that FAM122A may participate in the regulation of DNA homeostasis or stability. In this study, we continued to investigate

Epithelial-mesenchymal transition (EMT) is an important contributor to drug resistance in ovarian cancer. The aims of this study were to explore the potential role of the miR-302 cluster in modulating EMT and cisplatin resistance in ovarian cancer. We used qRT-PCR and western blotting to show that miR-302 expression was lower in chemoresistant than in chemosensitive cells, and miR-302 was upregulated

The proliferation and differentiation of myoblast cells are regulated by the fibroblast growth factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling

The 5′ untranslated region (5′UTR) is critical in determining post-transcriptional control, which is partly mediated by short upstream open reading frames (uORFs) present in half of mammalian transcripts. uORFs are generally considered to provide functionally important repression of the main-ORF by engaging initiating ribosomes, but under specific environmental conditions such as cellular stress, uORFs

Circular RNAs (circRNAs) are important players in prostate cancer (PCa) development and progression, but their detailed mechanisms have not been elucidated. Herein, hsa_circ_0007494 was suppressed in the PCa cell lines and tissues. This resulted in metastasis of tumors to the lymph node and predicted tumor stage. Functionally, overexpression of hsa_circ_0007494 inhibited the proliferation and invasive

Skeletal muscle preservation is a dynamic process that involves constant repair and regeneration. However, the regenerative capacity of muscle cells declines in hyperglycemia. This study aimed to explore the molecular mechanisms underlying this glucotoxicity during myoblast differentiation. C2C12 cells were exposed to different concentrations of glucose, to recapitulate the development of skeletal

Cells are continuously subject to various stresses, battling both exogenous insults as well as toxic by-products of normal cellular metabolism and nutrient deprivation. Throughout the millennia, cells developed a core set of general stress responses that promote survival and reproduction under adverse circumstances. Past and current research efforts have been devoted to understanding how cells sense

Sprifermin is a human recombinant fibroblast growth factor 18 (rhFGF18) in clinical development for knee osteoarthritis. Previously, we demonstrated that sprifermin exerts an anabolic effect on chondrocytes in 3D culture with cyclic but not permanent exposure. Here, we hypothesized that permanent exposure to sprifermin de-sensitizes the cells. To test this, a combination of Western-blot and cell staining

Background This study was aimed to identify an accurate gene expression signature to predict overall survival (OS) in patients with ovarian cancer (OC). Methods Expression data and corresponding clinical information were obtained from two independent databases: the Cancer Genome Atlas (TCGA) dataset and International Cancer Genome Consortium (ICGC) dataset. Multiple analysis methods including univariate

Human class I homeobox A13 (HOXA13) was initially identified as a transcription factor and has an important role in embryonic development and malignant transformation. However, the clinical significance and the molecular mechanisms of HOXA13 in colon cancer development and progression are still unknown. In this study, we found that HOXA13 was highly expressed in colon cancer tissues, and its expression

Our present study investigated whether exosome secretion of nucleus pulposus cells (NPCs) is regulated by autophagy. Different autophagic states of NPCs were induced by rapamycin (Rap), bafilomycin A1 (Baf) and other agents, and it was found that exosomes were secreted in an autophagy-dependent manner. Activation or inhibition of autophagy increased or decreased, respectively, the amount of exosomes

Increasing evidence has shown that abnormal expression of XPO5 is found in many human cancers and acts as an oncoprotein in certain cancers. However, its functional role in hepatocellular carcinoma (HCC) remains unexplored. In our study, we found that XPO5 was highly expressed in HCC, which was associated with SUMO modification. Moreover, we found that XPO5 was SUMOylated by SUMO2 at K125. Functional