Lung cancer remains one of the most common malignancies and the leading cause of cancer-related death worldwide. Forkhead box protein A1 (FOXA1) is a pioneer factor amplified in lung adenocarcinoma ...(LUAD). However, its role in LUAD remains elusive. In this study, we found that expression of FOXA1 enhanced LUAD cell survival in nutrients deprived conditions through inhibiting autophagic cell death (ACD). FOXA1 bound to the imprinting control region of insulin-like growth factor 2 (IGF2) and interacted with DNA methyltransferase 1 (DNMT1), leading to initiation of DNMT1-mediated loss of imprinting (LOI) of IGF2 and autocrine of IGF2. Blockage of IGF2 and its downstream insulin-like growth factor 1 receptor (IGF1R) abolished the protective effect of FOXA1 on LUAD cells in nutrients deprived conditions. Furthermore, FOXA1 suppressed the expression of the lysosomal enzyme glucocerebrosidase 1 (GBA1), a positive mediator of ACD, through ubiquitination of GBA1 enhanced by IGF2. Notably, FOXA1 expression in A549 cells reduced the efficacy of the anti-angiogenic drug nintedanib to inhibit xenograft tumor growth, whereas a combination of nintedanib with IGF1R inhibitor linsitinib or mTORC1 inhibitor rapamycin enhanced tumor control. Clinically, high expression level of FOXA1 protein was associated with unfavorable prognosis in LUAD patients of advanced stage who received bevacizumab treatment. Our findings uncovered a previously unrecognized role of FOXA1 in mediating loss of imprinting of IGF2, which confer LUAD cells enhanced survival ability against nutrients deprivation through suppressing autophagic cell death.
The cyclic signal amplification technology has been widely applied for the ultrasensitive detection of many important biomolecules, such as nucleic acids, proteins, enzymes, adenosine triphosphate ...(ATP), metal ions, exosome, etc. Due to their low content in the complex biological samples, traditional detection methods are insufficient to satisfy the requirements for monitoring those biomolecules. Therefore, effective and sensitive biosensors based on cyclic signal amplification technology are of great significance for the quick and simple diagnosis and treatment of diseases. Fluorescent biosensor based on cyclic signal amplification technology has become a research hotspot due to its simple operation, low cost, short time, high sensitivity and high specificity. This paper introduces several cyclic amplification methods, such as rolling circle amplification (RCA), strand displacement reactions (SDR) and enzyme-assisted amplification (EAA), and summarizes the research progress of using this technology in the detection of different biomolecules in recent years, in order to provide help for the research of more efficient and sensitive detection methods.
Inhibin B (INHBB), a heterodimer of a common α‐subunit and a βB‐subunit, is a glycoprotein belonging to the transforming growth factor‐β (TGF‐β) family. In this study, we observed INHBB expression ...was reduced in nasopharyngeal carcinoma (NPC) tissues compared to non‐tumor nasopharyngeal epithelium tissues, and INHBB was associated with lymph node metastasis, stage of disease, and clinical progress. Positive expression of INHBB in NPC predicted a better prognosis (overall survival, P = 0.038). However, the molecular mechanisms of INHBB have not been addressed in NPC. We induced anoikis‐resistant cells in NPC cell lines under anchorage‐independent conditions, then found epithelial‐mesenchymal transition markers changed, cell apoptosis decreased, cell cycle was modified, and invasion strengthened in anoikis‐resistant NPC cells. These anoikis‐resistant NPC cells showed decreased expression of INHBB compared with adhesion cells. Furthermore, INHBB was found to influence the above‐mentioned changes. In the anoikis‐resistant NPC cells with INHBB overexpression, apoptotic cells increased, S phase cells weakened, vimentin, matrix metallopeptidase‐9, and vascular endothelial growth factor A expression were downregulated, and E‐cadherin expression was upregulated, and vice versa in knockdown of INHBB (INHBB shRNA) anoikis‐resistant NPC cells. Diminished INHBB expression could activate the TGF‐β pathway to phosphorylate Smad2/3 and form complexes in the nucleus, which resulted in the above changes. Thus, our results revealed for the first time that INHBB could suppress anoikis resistance and migration of NPC cells by the TGF‐β signaling pathway, decrease p53 overexpression, and could serve as a potential biomarker for NPC metastasis and prognosis as well as a therapeutic application.
Our results showed for the first time that inhibin B could suppress anoikis resistance and migration of nasopharyngeal carcinoma cells by the transforming growth factor‐β signaling pathway, and decrease p53 overexpression. Inhibin B could serve as a potential biomarker for nasopharyngeal carcinoma metastasis and prognosis, as well as a therapeutic application.
More studies have shown that serum calcium has a crucial role in many types of cancers. However, few studies have determined the association between serum calcium levels and renal impairment (RI) and ...all-cause death in Chinese patients with multiple myeloma (MM).
A total of 246 of 565 participants who were followed for > 6 months from a MM cohort at our institution were eligible for the retrospective study. A generalized additive model and smooth curve fitting were performed to investigate the cross-sectional relationship between the serum calcium level and RI at baseline. Multivariate-adjusted Cox regression models were fitted to assess the associations between baseline serum calcium levels and the onset of end-stage renal disease (ESRD) or death in patients with MM.
A total of 172 of 565 patients (30.4%) with newly diagnosed MM presented with RI. The mean duration of follow-up was 26.64 months. Twenty-one patients (8.54%) died and 28 patients (11.52%) had ESRD. In patients with a serum calcium level > 2.30 mmol/L, the serum calcium level was independently associated with the occurrence of MM-related RI. Cox regression analysis showed that baseline serum calcium levels were consistently associated with a higher risk of all-cause death in the fully adjusted model, but were not associated with the occurrence of ESRD. When patients were categorized into two groups according to baseline mean serum calcium level, deaths occurred in 13 patients (15.1%) with a mean serum calcium level > 2.44 mmol/L compared to eight patients (5.0%) with a mean serum calcium level < 2.44 mmol/L (p < 0.05); Eighteen patients (11.46%) with a mean serum calcium level < 2.44 mmol/L progressed to ESRD compared to 13 patients (11.6%) with a serum calcium level > 2.44 mmol/L (p > 0.05).
This observational study showed that there was a nonlinear relationship between the serum calcium level and the presence of RI in patients with MM. An elevated baseline calcium level predicted all-cause death, but did not predict the occurrence of ESRD in patients with MM followed for > 6 months.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC) tumorigenesis. However, the mechanism(s) connecting EBV infection and NPC remain unclear. Recently, a new class of EBV ...microRNAs (miRNAs) has been described. To determine how EBV miRNAs control the expression of host genes, and to understand their potential role in NPC tumorigenesis, we profiled the expression of 44 mature EBV miRNAs and potential host genes in NPC and non-tumor nasopharyngeal epithelial tissues. We found that 40 EBV miRNAs from the BART transcript were highly expressed in NPC. Analysis of potential BART miRNA target genes revealed that 3140 genes and several important pathways might be involved in the carcinogenesis of NPC. A total of 105 genes with potential EBV miRNA binding sites were significantly downregulated, suggesting that EBV miRNAs may regulate these genes and contribute to NPC carcinogenesis. An EBV miRNA and host gene regulation network was generated to provide useful clues for validating of EBV miRNA functions in NPC tumorigenesis.
microRNAs (miRNAs) are small non-coding RNAs and have been implicated in the pathology of various diseases, including cancer. Here we report that the miRNA profiles have been changed after knockdown ...of one of the most important oncogene c-MYC or re-expression of a candidate tumor suppressor gene SPLUNC1 in nasopharyngeal carcinoma (NPC) cells. Both c-MYC knockdown and SPLUNC1 re-expression can down-regulate microRNA-141 (miR-141). miR-141 is up-regulated in NPC specimens in comparison with normal nasopharyngeal epithelium. Inhibition of miR-141 could affect cell cycle, apoptosis, cell growth, migration and invasion in NPC cells. We found that BRD3, UBAP1 and PTEN are potential targets of miR-141, which had been confirmed following luciferase reporter assays and western blotting. BRD3 and UBAP1 are both involved in NPC carcinogenesis as confirmed through our previous studies and PTEN is a crucial tumor suppressor in many tumor types. BRD3 is involved in the regulation of the Rb/E2F pathway. Inhibition of miR-141 could affect some important molecules in the Rb/E2F, JNK2 and AKT pathways. It is well known that carcinogenesis of NPC is involved in the networks of genetic and epigenetic alteration events. We propose that miR-141- and tumor-related genes c-MYC, SPLUNC1, BRD3, UBAP1 and PTEN may constitute a gene–miRNA network to contribute to NPC development.
In recent years, heptafluoroisobutyronitrile (C
3
F
7
CN) has been proved to be a potential eco-friendly insulating medium to replace sulfur hexafluoride (SF
6
, the strong greenhouse gas). In this ...paper, the effect of micro-H
2
O and micro-O
2
on the decomposition of C
3
F
7
CN was investigated based on the reactive force field molecular dynamics (ReaxFF-MD) and transition state theory (TST). It was found that H
2
O obviously promoted the decomposition of C
3
F
7
CN, and new products HF, COF
2
, CO, and NO were generated. The influence of O
2
on the C
3
F
7
CN dissociation was weaker than that of H
2
O, and O
2
slightly promoted the C
3
F
7
CN decomposition only when 50 O
2
molecules were added. The simultaneous presence of H
2
O and O
2
promoted the decomposition of C
3
F
7
CN, the promotion of which was closed to H
2
O existing alone. The calculation results showed that the energy barriers of the two reactions forming COF
2
were 31.38 kcal/mol and 23.85 kcal/mol, respectively, which indicated that the reactions were difficult to proceed spontaneously. The energy barrier of F + H
2
O → HF + OH was relatively lower than that of COF
2
. These values corresponded well to the ReaxFF simulation results. This study provides theoretical support for the effect of H
2
O and O
2
on the decomposition of C
3
F
7
CN.
YAP at the progression of inflammation Chen, Libin; Jin, Xintong; Ma, Jian ...
Frontiers in cell and developmental biology,
06/2023, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
Yes-associated protein (YAP) is a transcriptional regulator that affects cell proliferation, organ size and tissue development and regeneration, and has therefore, been an important object of study. ...In recent years, there has been an increasing research focus on YAP in inflammation and immunology, and the role of YAP in the development of inflammation and in immune escape by tumors has been progressively elucidated. Because YAP signaling involves a variety of different signal transduction cascades, the full range of functions in diverse cells and microenvironments remains incompletely understood. In this article, we discuss the complex involvement of YAP in inflammation, the molecular mechanisms through which it exercises pro- and anti-inflammatory effects under different conditions, and the progress achieved in elucidating the functions of YAP in inflammatory diseases. A thorough understanding of YAP signaling in inflammation will provide a foundation for its use as a therapeutic target in inflammatory diseases.
Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with ...nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway.
An association between carcinogenesis and inflammation has long been appreciated. Chemically induced colitis-associated cancer (CAC) is a classical mouse model for investigating 'inflammation-cancer ...link' in the intestine. Diverse mechanisms behind this non-resolving inflammation model have been reported before, most of them were emphasized on key cancer genes, cytokines, and signal transduction abnormality based on prior knowledge. In this study, we dynamically and globally dissect the alteration of key pathways in the development from colitis to colorectal cancer. Striking evidence from gene expression profiling, serum cytokines detection, and immunohistochemistry analysis all reveals that different key pathways NF-κB, STAT3, p38 mitogen-activated protein kinase (MAPK), and Wnt/β-catenin signaling and their target genes are hyperactive in different phases of the inflammation-cancer link. Nuclear factor-κB (NF-κB) and STAT3 signaling are hyperactive in the whole process, while p38 MAPK and Wnt/β-catenin signaling are only hyperactive in the beginning and ending, respectively. Through this unbiased system biological approach, we provide strong evidence that different key pathways are specifically involved in different phases, which bridge the gap between inflammation and cancer.
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