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Environmental Science & Technology Oct 2023Synthetic glucocorticoids have been widely detected in aquatic ecosystems and may pose a toxicological risk to fish. In the present study, we described multiple end...
Synthetic glucocorticoids have been widely detected in aquatic ecosystems and may pose a toxicological risk to fish. In the present study, we described multiple end point responses of zebrafish to a commonly prescribed glucocorticoid, prednisolone (PREL), at concentrations between 0.001 and 9.26 μg/L. Of 23 end points monitored, 7 were affected significantly. Significant increases in the frequency of yolk extension formation, spontaneous contraction, heart rate, and ocular melanin density and significant decreases of ear-eye distance at PREL concentrations of 0.001 μg/L and above clearly pointed to the acceleration of embryonic development of zebrafish by PREL. Further confirmation came from the alterations in somite numbers, head-trunk angle, and yolk sac size, as well as outcomes obtained via RNA sequencing, in which signaling pathways involved in tissue/organ growth and development were highly enriched in embryos upon PREL exposure. In addition, the crucial role of glucocorticoid receptor (GR) for PREL-induced effects was confirmed by both, the coexposure to antagonist mifepristone (RU486) and GR mutant zebrafish experiments. We further demonstrated similar accelerations of embryonic development of zebrafish upon exposure to 11 additional glucocorticoids, indicating generic adverse effect characteristics. Overall, our results revealed developmental alterations of PREL in fish embryos at low concentrations and thus provided novel insights into the understanding of the potential environmental risks of glucocorticoids.
Topics: Animals; Glucocorticoids; Prednisolone; Zebrafish; Receptors, Glucocorticoid; Ecosystem; Embryonic Development; Embryo, Nonmammalian
PubMed: 37812749
DOI: 10.1021/acs.est.3c02658 -
Molecular Carcinogenesis Nov 2023Cervical cancer is the fourth most common malignant tumors in female worldwide. Cirular RNAs (circRNA) represent a new class of regulatory RNA and play a pivotal role in...
Cervical cancer is the fourth most common malignant tumors in female worldwide. Cirular RNAs (circRNA) represent a new class of regulatory RNA and play a pivotal role in the carcinogenesis and development of tumors. However, their functions have not been fully elucidated in cervical cancer. In this study, we identified an upregulated circRNA, circ_0001589, both in fresh clinical samples and tissue microarray of cervical cancer. Transwell assay and cell apoptosis assay by flow cytometry demonstrated circ_0001589 promotes epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion, and enhanced cisplatin resistance in vitro. In addition, in nude mice model, circ_0001589 increased the number of lung metastases and recovered xenograft growth from cisplatin treatment in vivo. Mechanistically, RNA pull-down assay, RNA immunoprecipitation, and dual-luciferase reporter assay disclosed that circ_0001589 function as an competing endogenous RNA to sponge miR-1248, which directly target the 3' untranslated region of high mobility group box-B1 (HMGB1). Thereby, circ_0001589 upregulated HMGB1 protein expression and accelerate cervical cancer progression. The rescue experiments also revealed that miR-1248 overexpression or HMGB1 knockdown partially reversed the regulatory functions of circ_0001589 on cell migration, invasion, and cisplatin resistance. In summary, our findings suggest the upregulation of circ_0001589 promoted EMT-mediated cell migration and invasion, and enhanced cisplatin resistance via regulating miR-1248/HMGB1 axis in cervical cancer. These results provided new evidence for understanding the carcinogenesis mechanism and finding new therapeutic target for cervical cancer.
Topics: Animals; Female; Humans; Mice; 3' Untranslated Regions; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Cisplatin; Epithelial-Mesenchymal Transition; HMGB1 Protein; Mice, Nude; MicroRNAs; Rectal Neoplasms; RNA, Circular; Uterine Cervical Neoplasms
PubMed: 37431919
DOI: 10.1002/mc.23605 -
Environmental Research Sep 2023Colorectal cancer (CRC) ranks as the third most aggressive tumor globally, and it can be categorized into two forms: colitis-mediated CRC and sporadic CRC. The... (Review)
Review
Colorectal cancer (CRC) ranks as the third most aggressive tumor globally, and it can be categorized into two forms: colitis-mediated CRC and sporadic CRC. The therapeutic approaches for CRC encompass surgical intervention, chemotherapy, and radiotherapy. However, even with the implementation of these techniques, the 5-year survival rate for metastatic CRC remains at a mere 12-14%. In the realm of CRC treatment, gene therapy has emerged as a novel therapeutic approach. Among the crucial molecular pathways that govern tumorigenesis, STAT3 plays a significant role. This pathway is subject to regulation by cytokines and growth factors. Once translocated into the nucleus, STAT3 influences the expression levels of factors associated with cell proliferation and metastasis. Literature suggests that the upregulation of STAT3 expression is observed as CRC cells progress towards metastatic stages. Consequently, elevated STAT3 levels serve as a significant determinant of poor prognosis and can be utilized as a diagnostic factor for cancer patients. The biological and malignant characteristics of CRC cells contribute to low survival rates in patients, as the upregulation of STAT3 prevents apoptosis and promotes pro-survival autophagy, thereby accelerating tumorigenesis. Furthermore, STAT3 plays a role in facilitating the proliferation of CRC cells through the stimulation of glycolysis and promoting metastasis via the induction of epithelial-mesenchymal transition (EMT). Notably, an intriguing observation is that the upregulation of STAT3 can mediate resistance to 5-fluorouracil, oxaliplatin, and other anti-cancer drugs. Moreover, the radio-sensitivity of CRC diminishes with increased STAT3 expression. Compounds such as curcumin, epigallocatechin gallate, and other anti-tumor agents exhibit the ability to suppress STAT3 and its associated pathways, thereby impeding tumorigenesis in CRC. Furthermore, it is worth noting that nanostructures have demonstrated anti-proliferative and anti-metastatic properties in CRC.
Topics: Humans; Colorectal Neoplasms; Cell Transformation, Neoplastic; Apoptosis; Cytokines; Cell Proliferation; Cell Line, Tumor; STAT3 Transcription Factor
PubMed: 37348629
DOI: 10.1016/j.envres.2023.116458 -
Biochemical Genetics Aug 2023Cervical cancer (CC) is the fourth most common cancer in women, and circular RNAs (circRNAs) have been shown to regulate CC development. However, the role of...
Cervical cancer (CC) is the fourth most common cancer in women, and circular RNAs (circRNAs) have been shown to regulate CC development. However, the role of circ_0006646 in CC progression is still unclear. The levels of circ_0006646, miR-758-3p, and ribonucleotide reductase regulatory subunit M2 (RRM2) were evaluated by quantitative real-time PCR. Cell proliferation was tested by cell counting kit 8 and 5-ethynyl-2'-deoxyuridine assays. Flow cytometry was used to test cell apoptosis. Migration and invasion were estimated by transwell assay. Western blot assay was performed to examine protein expression. Dual-luciferase reporter assay, RIP assay, and RNA pull down assay were used to analyze the connection between miR-758-3p and circ_0006646 or RRM2. Tumor growth was detected by in vivo experiments. Exosomes were isolated form CC patients and healthy controls. Circ_0006646 expression was elevated in CC cells, and its knockdown suppressed CC cell growth, migration, and invasion. MiR-758-3p was sponged by circ_0006646, and RRM2 was targeted by miR-758-3p. In addition, the effects of circ_0006646 depletion on CC cell progression were overturned by miR-758-3p inhibitor, and either RRM2 overexpression reversed those effects of miR-758-3p overexpression on CC cell progression. Circ_0006646 was highly expressed in the exosomes of CC patients. Circ_0006646 expedited CC cell growth and metastasis by regulating miR-758-3p/RRM2 axis, and exosomal circ_0006646 might be a potential diagnostic indicator of CC.
Topics: Humans; Female; Uterine Cervical Neoplasms; Oxidoreductases; Cell Proliferation; Apoptosis; MicroRNAs; Cell Line, Tumor
PubMed: 36583788
DOI: 10.1007/s10528-022-10320-6 -
FASEB Journal : Official Publication of... Oct 2023Ovarian cancer (OC) is the second leading cause of gynecological cancer-related death in women worldwide. N6-methyladenosine (m A) is the most abundant internal...
Ovarian cancer (OC) is the second leading cause of gynecological cancer-related death in women worldwide. N6-methyladenosine (m A) is the most abundant internal modification in eukaryotic RNA. Human insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m A reader, can enhance mRNA stability and promote translation by recognizing m A modifications. Its tumor-promoting effects have been demonstrated in several cancers. However, the roles of m A modification and IGF2BP2 in OC remain unclear. Here, by using methylated RNA immunoprecipitation sequencing, we demonstrated that there is widespread dysregulation of m A modification in OC tissues. The m A modification and the mRNA and protein levels of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, and invasion in vitro and accelerated tumor growth and metastasis in vivo. While IGF2BP2-knockdown showed the opposite effect. Mechanistically, we identified cytoskeleton-associated protein 2-like (CKAP2L) as a target of IGF2BP2. IGF2BP2 promoted CKAP2L translation dependent on m A modification, rather than affecting mRNA and protein stability. Overexpression of CKAP2L rescued the tumor-suppressive effect of IGF2BP2 knockdown in OC cells. In conclusion, this study revealed the potential role of IGF2BP2 in tumor progression, at least partially via promoting the translation of CKAP2L in an m A-dependent manner.
Topics: Female; Humans; Adenosine; Cell Proliferation; Cytoskeletal Proteins; Immunoprecipitation; Ovarian Neoplasms; RNA-Binding Proteins
PubMed: 37665628
DOI: 10.1096/fj.202202145RRR -
Critical Reviews in Biotechnology Feb 2024Microorganisms play an important role in plant growth and development. In particular, endophytic fungi is one of the important kinds of microorganisms and has a mutually... (Review)
Review
Microorganisms play an important role in plant growth and development. In particular, endophytic fungi is one of the important kinds of microorganisms and has a mutually beneficial symbiotic relationship with host plants. Endophytic fungi have many substantial benefits to host plants, especially for woody plants, such as accelerating plant growth, enhancing stress resistance, promoting nutrient absorption, resisting pathogens and etc. However, the effects of endophytic fungi on the growth and development of woody plants have not been systematically summarized. In this review, the functions of endophytic fungi for the growth and development of woody plants have been mainly reviewed, including regulating plant growth (e.g., flowering, root elongation, etc.) by producing nutrients and plant hormones, and improving plant disease, insect resistance and heavy metal resistance by producing secondary metabolites. In addition, the diversity of endophytic fungi could improve the ability of woody plants to adapt to adverse environment. The components produced by endophytic fungi have excellent potential for the growth and development of woody plants. This review has systematically discussed the potential regulation mechanism of endophytic fungi regulating the growth and development of woody plants, it would be of great significance for the development and utilization of endophytic fungi resource from woody plants for the protection of forest resources.
Topics: Endophytes; Fungi; Plants; Symbiosis; Plant Development
PubMed: 36592988
DOI: 10.1080/07388551.2022.2129579 -
Nature Immunology Jun 2024The durability of an antitumor immune response is mediated in part by the persistence of progenitor exhausted CD8 T cells (Tpex). Tpex serve as a resource for...
The durability of an antitumor immune response is mediated in part by the persistence of progenitor exhausted CD8 T cells (Tpex). Tpex serve as a resource for replenishing effector T cells and preserve their quantity through self-renewal. However, it is unknown how T cell receptor (TCR) engagement affects the self-renewal capacity of Tpex in settings of continued antigen exposure. Here we use a Lewis lung carcinoma model that elicits either optimal or attenuated TCR signaling in CD8 T cells to show that formation of Tpex in tumor-draining lymph nodes and their intratumoral persistence is dependent on optimal TCR engagement. Notably, attenuated TCR stimulation accelerates the terminal differentiation of optimally primed Tpex. This TCR-reinforced Tpex development and self-renewal is coupled to proximal positioning to dendritic cells and epigenetic imprinting involving increased chromatin accessibility at Egr2 and Tcf1 target loci. Collectively, this study highlights the critical function of TCR engagement in sustaining Tpex during tumor progression.
Topics: Animals; CD8-Positive T-Lymphocytes; Receptors, Antigen, T-Cell; Mice; Carcinoma, Lewis Lung; Mice, Inbred C57BL; Hepatocyte Nuclear Factor 1-alpha; Cell Differentiation; Dendritic Cells; Signal Transduction; Mice, Knockout; Lymphocyte Activation; Cell Self Renewal; Mice, Transgenic; Early Growth Response Protein 2
PubMed: 38816618
DOI: 10.1038/s41590-024-01843-8 -
Immunity, Inflammation and Disease Oct 2023Mechanical ventilation is an important means of respiratory support and treatment for various diseases. However, its use can lead to serious complications, especially... (Review)
Review
BACKGROUND
Mechanical ventilation is an important means of respiratory support and treatment for various diseases. However, its use can lead to serious complications, especially ventilator-induced lung injury (VILI). The mechanisms underlying this disease are complex, but activation of inflammatory signalling pathways results in activation of cytokines and inflammatory mediators, which play key roles in VILI. Recent studies have demonstrated that nod-like receptor protein 3 (NLRP3) inflammasome activation mediates VILI and also accompanied by cell proliferation and transdifferentiation to compensate for alveolar membrane damage. Type I alveolar epithelial cells (AECs I), which are involved in the formation of the blood-air barrier, are vulnerable to damage but cannot proliferate by themselves; thus, replacing AECs I relies on type II alveolar epithelial cells (AECs II).
OBJECTIVE
The review aims to introduce the mechanisms of NLRP3 inflammasome activation and its inhibitors, as well as the mechanisms that regulate cell proliferation and transdifferentiation.
METHODS
A large number of relevant literature was searched, then the key content was summarized and figures were also made.
RESULTS
The mechanism of NLRP3 inflammasome activation has been further explored, including but not limited to pathogenic and aseptic inflammatory signals, such as, pathogenic molecular patterns and host-derived danger-associated molecular patterns activate toll-like receptor 4/nuclear factor-kappaB pathway or reactive oxygen species, cyclic stretch, adenosine triphosphate induce K+ efflux through P2X7, Ca inflow, mitochondrial damage, etc, eventually induce NIMA-related kinase 7/NLRP3 binding and NLRP3 inflammasome activation. Not only that, the review also described in detail the inhibitors of NLRP3 inflammasome. And the mechanisms regulating cell proliferation and transdifferentiation are complex and unclear, including the Wnt/β-catenin, Yap/Taz, BMP/Smad and Notch signalling pathways.
CONCLUSIONS
NLRP3 inflammasome activation mediated VILI, and VILI is alleviated after interfering with its activation, and inflammation and repair exist simultaneously in VILI. Clarifying these mechanisms is expected to provide theoretical guidance for alleviating VILI by inhibiting the inflammatory response and accelerating alveolar epithelial cell regeneration in the early stage.
Topics: Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; NLR Proteins; Cell Transdifferentiation; Ventilator-Induced Lung Injury; Cell Proliferation
PubMed: 37904713
DOI: 10.1002/iid3.1062 -
Thoracic Cancer Oct 2023The aim of this study was to explore the function and mechanism of circular RNA (circRNA) matrix metallopeptidase 1 (circMMP1) in the progression of esophageal squamous...
BACKGROUND
The aim of this study was to explore the function and mechanism of circular RNA (circRNA) matrix metallopeptidase 1 (circMMP1) in the progression of esophageal squamous cell carcinoma (ESCC).
METHODS
CircMMP1 expression was detected by quantitative real-time PCR (qRT-PCR), and its relationship with the prognosis of ESCC patients was evaluated by Kaplan-Meier analysis. Cells were transfected using corresponding plasmids, and the cell proliferation activity, migration and invasion capabilities in vitro were assessed. The protein level in tissues and cells was analyzed using western blotting. RNA pulldown, dual-luciferase reporter assay and RNA immunoprecipitation assay were performed in ESCC cells to detect the interaction between circMMP1 and miR-671-5p, or the correlation between miR-671-5p and ANO1. Xenograft tumor experiment was carried out to uncover the function of circMMP1 in vivo.
RESULTS
The high level of circMMP1 in tumor tissues was associated with poor prognoses of ESCC patients. Knockdown of circMMP1 suppressed ESCC cell proliferation, migration and invasion in vitro. MiR-671-5p was the target of circMMP1 and mediated the inhibition effect of circMMP1 on ESCC cells. CircMMP1 targeted miR-671-5p to regulate ANO1 expression, which was downstream of miR-671-5p. Overexpression of ANO1 weakened tumor-repressive function of circMMP1 knockdown in ESCC cells. Moreover, silencing of circMMP1 impeded ESCC tumor growth in vivo.
CONCLUSION
Our study provided novel evidence that circMMP1 accelerated ESCC progression by acting as a miR-671-5p sponge to enhance ANO1 expression.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; MicroRNAs; Cell Proliferation; Prognosis; Cell Line, Tumor; Gene Expression Regulation, Neoplastic
PubMed: 37635445
DOI: 10.1111/1759-7714.15078 -
Histology and Histopathology Oct 2023Circular RNAs (circRNAs) are key molecules in the regulation of intrahepatic cholangiocarcinoma (ICC) progression. The purpose of this study was to analyze the function...
BACKGROUND
Circular RNAs (circRNAs) are key molecules in the regulation of intrahepatic cholangiocarcinoma (ICC) progression. The purpose of this study was to analyze the function and underlying molecular mechanism of circ_0000284 in ICC.
METHODS
Quantitative real-time PCR was used to analyze the circ_0000284, microRNA (miR)-152-3p and pyruvate dehydrogenase kinase 1 (PDK1) expression. Cell proliferation, apoptosis, invasion and migration were executed by cell counting kit 8 assay, EdU assay, flow cytometry, transwell assay and wound healing assay, respectively. All protein expression levels were examined using western blot analysis. Cell glycolysis was analyzed by detecting glucose consumption, lactate production and ATP/ADP ratios. Target relationship was estimated by dual-luciferase reporter assay. The effect of circ_0000284 on ICC tumor growth in vivo was evaluated by constructing xenograft mice model.
RESULTS
We detected high expression of circ_0000284 in ICC tumor tissues and cells. Downregulated circ_0000284 inhibited ICC cell proliferation, invasion, migration, glycolysis, and accelerated apoptosis. MiR-152-3p was sponged by circ_0000284, and its inhibitor revoked the effect of circ_0000284 knockdown on ICC cell progression. PDK1 was a target of miR-152-3p, and its expression was suppressed by circ_0000284 knockdown. PDK1 overexpression reversed the inhibition effect of miR-152-3p on ICC cell growth, metastasis and glycolysis. In animal experiments, circ_0000284 downregulation also inhibited ICC tumor growth.
CONCLUSION
Circ_0000284 promoted the growth, metastasis and glycolysis of ICC by miR-152-3p/PDK1 pathway, showing that circ_0000284 was a potential therapeutic target for ICC.
Topics: Animals; Humans; Mice; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cell Line, Tumor; Cell Proliferation; Cholangiocarcinoma; Disease Models, Animal; Glycolysis; Lactic Acid; MicroRNAs
PubMed: 36331285
DOI: 10.14670/HH-18-544