RESUMO
Golden pompano is an important aquaculture product in the coastal regions of southern China, which is highly dependent on insulin-like growth factor (IGF) for various biological processes. The cDNAs of ToIGF1, ToIGF2, and ToIGF3 are 1718 bp, 1658 bp, and 2272 bp in length, respectively, with corresponding amino acid sequences of 185 aa, 215 aa, and 194 aa. These sequences consist of 5 parts, including the signal peptide, the B domain, the C domain, the A domain, the D domain, and the E domain, which are also found in other species. While ToIGF1 has no SSR polymorphism, ToIGF2 and ToIGF3 have 3 and 1 SSR polymorphism sites, respectively. In terms of tissue expression, ToIGF1 is predominantly expressed in the liver, ToIGF2 shows its highest expression in the gills, and ToIGF3 also shows its highest expression in the gills, but no expression in the liver and spleen. These tissue distribution results suggest that ToIGFs are not only present in growth-related tissues such as the brain, muscle, and liver, but also in reproductive tissues, tissues that regulate osmotic pressure, and tissues related to food intake. This observation is consistent with other bony fish species and highlights the extensive biological functions of ToIGFs that need to be further explored and exploited. In addition, the expression levels of ToIGFs were found to be different in the different dietary groups, including the pelleted food group, the frozen squid group, and the frozen fish group. In the pelleted diet group, ToIGF1 and ToIGF2 were highly expressed in the liver and intestinal tissues, followed by the frozen fish group. These results suggest that the type of diet can affect the body's energy metabolism by influencing tissue expression of growth-related genes, which in turn affects individual growth.
Assuntos
Ração Animal , Animais , Ração Animal/análise , Peixes/genética , Peixes/metabolismo , Somatomedinas/metabolismo , Somatomedinas/genética , Dieta/veterinária , Sequência de Aminoácidos , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Filogenia , Peptídeos Semelhantes à InsulinaRESUMO
External and internal factors are involved in controlling the growth of fishes. However, little is known about the mechanisms by which external factors trigger stimulus signals. This study explored the physiological roles of melatonin in the transcription of growth-related genes in the brain and liver of Chrysiptera cyanea, a tropical damselfish with long-day preference. In brain samples of this species collected at 4-h intervals, the transcript levels of arylalkylamine N-acetyltransferase2 (aanat2), the rate-limiting enzyme of melatonin synthesis, and growth hormone (gh) peaked at 20:00 and 00:00, respectively. Concomitantly, the transcript levels of insulin-like growth factors (igf1 and igf2) in the brain and liver were upregulated during the scotophase. Levels of iodothyronine deiodinases (dio2 and dio3), enzymes that convert thyroxine (T4) to triiodothyronine (T3) and reverse T3, respectively, increased in the brain (dio2 and dio3) and liver (dio2) during the photophase, whereas dio3 levels in the liver showed the opposite trend. Fish reared in melatonin-containing water exhibited significant increases in the transcription levels of gh and igf1 in the brain and igf1 in the liver, suggesting that growth in this fish is positively regulated by the GH/IGF pathway on a daily basis. Melatonin treatment also stimulated the transcript levels of dio2 and dio3 in the liver, but not in the brain. Fish consuming pellets containing T3, but not T4, showed significant increases in gh and igf1 in the brain and igf1 and igf2 in the liver, suggesting that the intercellular actions of the TH/IGF pathway have an impact on growth on a daily basis. In summary, IGF synthesis and action in the brain and liver undergo dual regulation by distinct hormone networks, which may also be affected by daily, seasonal, or nutritional factors.
Assuntos
Encéfalo , Fígado , Melatonina , Somatomedinas , Hormônios Tireóideos , Animais , Melatonina/metabolismo , Fígado/metabolismo , Encéfalo/metabolismo , Encéfalo/crescimento & desenvolvimento , Hormônios Tireóideos/metabolismo , Somatomedinas/metabolismo , Somatomedinas/genética , Arilalquilamina N-Acetiltransferase/metabolismo , Arilalquilamina N-Acetiltransferase/genética , Perciformes/metabolismo , Perciformes/genética , Perciformes/crescimento & desenvolvimento , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/genética , Iodeto Peroxidase/metabolismo , Iodeto Peroxidase/genética , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like II/genética , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/genética , Transdução de Sinais , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Peptídeos Semelhantes à InsulinaRESUMO
BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a common malignant tumor associated with EBV infection. Insulin-like growth factor 2 (IGF2) is an imprinted gene and a key protein that regulates growth, especially during normal fetal development. Loss of imprinting (LOI), is a common epigenetic anomaly in a variety of human cancers. However, the promoter methylation, imprinting status and function of IGF2 gene in GC are unclear. OBJECTIVE: To explore the role of IGF2 in the occurrence and development of gastric cancer. METHODS: The biological function of IGF2 in gastric cancer was investigated by Transwell, wound healing, CCK-8 and flow cytometry assays. IGF2 imprinting status and gene promoter methylation in gastric cancer tissues were detected by PCR-RFLP and BGS. RESULTS: The results showed that the expression of IGF2 was higher in GC tissues than adjacent tissues. IGF2 gene promoter methylation and LOI were significantly higher in EBVaGC tissues than in EBV-negative gastric cancer (EBVnGC) tissues. The high expression of IGF2 in gastric cancer can promote the migration and proliferation of gastric cancer cells. CONCLUSION: Our data suggest that IGF2 is involved in the occurrence and development of gastric cancer. Targeting IGF2 may be a potential therapeutic target for gastric cancer.
Assuntos
Fator de Crescimento Insulin-Like II , Neoplasias Gástricas , Feminino , Humanos , Gravidez , Metilação de DNA , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Impressão Genômica , Herpesvirus Humano 4/genética , Somatomedinas/genética , Neoplasias Gástricas/genética , Fator de Crescimento Insulin-Like II/genéticaRESUMO
Breeding program to improve economically important growth traits in striped catfish (Pangasianodon hypophthalmus) requires effective molecular markers. This study was conducted to identify single nucleotide polymorphisms (SNPs) of Insulin-like Growth Factor-Binding Protein 7 (IGFBP7) gene which plays multiple roles in regulating growth, energy metabolism and development. The association between SNPs in IGFBP7 gene and growth traits in striped catfish was analyzed in order to uncover the SNPs that have potential to be valuable markers for improving growth traits. Firstly, fragments of IGFBP7 gene from ten fast-growing fish and ten slow-growing fish were sequenced in order to discover SNPs. After filtering the detected SNPs, an intronic SNP (2060A > G) and two non-synonymous SNPs (344 T > C and 4559C > A) causing Leu78Pro and Leu189Met in protein, respectively, were subjected to further validated by individual genotyping in 70 fast-growing fish and 70 slow-growing fish using single base extension method. Our results showed that two SNPs (2060A > G and 4559 C > A (p. Leu189Met)) were significantly associated with the growth in P. hypophthalmus (p < 0.001), thus being candidate SNP markers for the growth traits of this fish. Moreover, linkage disequilibrium and association analysis with growth traits of haplotypes generated from the 3 filtered SNPs (344 T > C, 2060 A > G and 4559 C > A) were examined. These revealed that the non-coding SNP locus (2060A > G) had higher genetic diversity at which the G allele was predominant over the A allele in the fast-growing fish. Furthermore, the results of qPCR showed that expression of IGFBP7 gene with genotype GG (at locus 2060) in fast-growing group was significantly higher than that with genotype AA in slow-growing group (p < 0.05). Our study provides insights into the genetic variants of IGFBP7 gene and useful data source for development molecular marker for growth traits in breeding of the striped catfish.
Assuntos
Peixes-Gato , Somatomedinas , Animais , Peixes-Gato/genética , Polimorfismo de Nucleotídeo Único/genética , Fenótipo , Genótipo , Somatomedinas/genéticaRESUMO
AIMS: To examine associations between the transcription factors CCCTC-binding factor (CTCF) and forkhead box protein A1 (FOXA1) and the androgen receptor (AR) and their association with components of the insulin-like growth factor (IGF)-pathway in a cohort of men with localized prostate cancer. METHODS: Using prostate tissue samples collected during the Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) trial (N = 70 to 92, depending on section availability), we assessed the abundance of CTCF, FOXA1, AR, IGFIR, p-mTOR, PTEN and IGFBP-2 proteins using a modified version of the Allred scoring system. Validation studies were performed using large, publicly available datasets (TCGA) (N = 489). RESULTS: We identified a strong correlation between CTCF and AR staining with benign prostate tissue. CTCF also strongly associated with the IGFIR, with PTEN and with phospho-mTOR. FOXA1 was also correlated with staining for the IGF-IR, with IGFBP-2 and with staining for activated phosphor-mTOR. The staining for the IGF-IR was strongly correlated with the AR. CONCLUSION: Our findings emphasise the close and complex links between the endocrine controls, well known to play an important role in prostate cancer, and the transcription factors implicated by the recent genetic evidence.
Assuntos
Neoplasias da Próstata , Somatomedinas , Masculino , Humanos , Androgênios , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Ligação a CCCTC/genética , Linhagem Celular Tumoral , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Somatomedinas/genética , Somatomedinas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismoRESUMO
The role and mechanism of insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) in the metastasis of esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, IGF2BP3 mRNA and protein expression levels were evaluated in ESCC tissues. Small interfering RNAs (siRNAs), plasmid overexpression, and stable lentivirus transfection were used to manipulate intracellular IGF2BP3 expression levels. The role of IGF2BP3 in ESCC tumorigenesis was investigated in vitro and in vivo. IGF2BP3 target transcripts were detected, and the acetylation effect ratios of the IGF2BP3 promoter region by H3K27ac were determined. IGF2BP3 mRNA expression levels were significantly higher in ESCC tissues than in normal esophageal tissues. Increased IGF2BP3 expression levels were detected in node-negative ESCC tissues and correlated with greater lesion depth in ESCC. Overexpression of IGF2BP3 promoted ESCC development in vitro and in vivo, and IGF2BP3 knockdown caused an opposite effect. IGF2BP3 was found to directly bind to the zinc finger E-box-binding homeobox 1 (Zeb1) mRNA, and the downregulation of IGF2BP3 reduced the stability of Zeb1 mRNA. IGF2BP3 induced epithelial-mesenchymal transition in ESCC cells in a Zeb1-dependent manner. IGF2BP3 was transcriptionally activated in ESCC cell lines via H3K27 acetylation. Our results demonstrate that IGF2BP3 plays a vital role in ESCC cell proliferation, invasion, and metastasis and is a potential therapeutic target for treating ESCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Somatomedinas , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas/metabolismo , Transição Epitelial-Mesenquimal/genética , RNA Mensageiro/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Somatomedinas/genética , Somatomedinas/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/genéticaRESUMO
Insulin-like growth factor 3 plays an important role in gonad development in teleost fish. Previous studies found that igf3 was specifically expressed in gonads of silver pomfret (Pampus argenteus). Unlike in other fish, IGF3 is a membrane protein in silver pomfret, and its specific role in gonads is unclear. Herein, we explored the importance of IGF3 in oogenesis and spermatogenesis in silver pomfret by analyzing gene expression and cellular localization. During follicular development, igf3 was detected in ovaries at both mRNA and protein levels during the critical stages of vitellogenesis (IV-VI). Localization analysis detected igf3 mRNA and protein in somatic cells, including theca and granulosa cells around oocytes. Similar to cathepsin L and cathepsin K, igf3 was consistently expressed in ovaries during vitellogenesis, suggesting that it might play a key role in vitellogenesis of oocytes. During spermatogenesis, igf3 mRNA and protein levels were high in stages II, IV, and V, similar to sycp3 and dmc1, and the highest igf3 mRNA and protein levels were reached in stage VI. Furthermore, igf3 mRNA and protein were detected in spermatogonia, spermatocytes, spermatids, and surrounding Sertoli cells, but not in spermatozoon, indicating that IGF3 might be involved in differentiation and meiosis of spermatogonia.
Assuntos
Perciformes , Somatomedinas , Masculino , Feminino , Animais , Catepsina L/metabolismo , Catepsina K/metabolismo , Estações do Ano , Somatomedinas/genética , Somatomedinas/metabolismo , Gônadas/metabolismo , Perciformes/genética , Perciformes/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Peixes/metabolismo , Proteínas de Membrana/metabolismoRESUMO
The role of insulin/insulin-like growth factor (IGF) signaling pathway in the growth regulation of marine invertebrates has not been fully studied. In this study, the economically important species Ruditapes philippinarum was sacrificed to clarify the role of IGF system in the growth regulation of R. philippinarum by real-time quantitative PCR. Systematic bioinformatics analysis can identify the major genes of IGF signaling pathway and insulin-like peptide receptor (ILPR) - mediated signaling pathway in R. philippinarum. The expression levels of IGF and its downstream signaling pathway genes in larger clams were significantly higher than those in small clams, indicating that they were involved in the growth regulation of R. philippinarum. These results suggest that IGF signaling pathway and ILPR mediated signaling pathway to regulate the growth of R. philippinarum.
Assuntos
Bivalves , Somatomedinas , Animais , Bivalves/genética , Bivalves/metabolismo , Insulina/genética , Receptores de Peptídeos , Transdução de Sinais , Somatomedinas/genética , Somatomedinas/metabolismoRESUMO
OBJECTIVES: Neuroblastoma (NB) is one of the most common extracranial malignant tumors in children and remarkable heterogeneous tumor of the sympathetic nervous system. Long noncoding RNAs (lncRNAs) have been reported to be vital biological roles in the initiation and malignant progression of tumors. The aim of this study was to explore the biological role and the possible molecular mechanism of LINC00200 in NB. DESIGN & METHODS: The expression level of LINC00200 in NB tissues and cell lines were detected by real-time quantitative PCR (qRT-PCR). The biological effects of LINC00200 on NB cell proliferation, migration and invasion were examined by EdU and transwell assays. The molecular mechanism of LINC00200 in NB were explored and verified by bioinformatics analysis, RNA binding protein immunoprecipitation (RIP) assay and RNA pull down assay. RESULTS: The results showed that the expression of LINC00200 was significantly higher in NB tissues than in normal tissues. Besides, the expression of LINC00200 was higher in MYCN Amplified NB tissues than in MYCN non-Amplified NB tissues. Moreover, overexpression of LINC00200 could remarkedly promote proliferation, migration and invasion of NB cell. Mechanistically, LINC00200 might bind to RNA binding protein (RBP) IGF2BP3 and promote the expression of ZIC2. CONCLUSIONS: Overall, we showed that LINC00200 was upregulated in NB tissues and the LINC00200/IGF2BP3/ZIC2 regulatory axis might be the possible therapeutic target for NB.
Assuntos
Neuroblastoma , RNA Longo não Codificante , Somatomedinas , Criança , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Família , Regulação Neoplásica da Expressão Gênica/genética , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Proteínas Nucleares/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Somatomedinas/genética , Somatomedinas/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Both genomics- and proteomics-based investigations have identified several essential genes, proteins, and pathways that may facilitate human adaptive genotype/phenotype in a population-specific manner. This comprehensive review provides an up-to-date list of genes and proteins identified for human adaptive responses to high altitudes. Genomics studies for indigenous high-altitude populations like Tibetans, Andeans, Ethiopians, and Sherpas have identified 169 genes under positive natural selection. Similarly, global proteomics studies have identified 258 proteins (± 1.2-fold or more) for Tibetan, Sherpa, and Ladakhi highlanders. The primary biological processes identified for genetic signatures include hypoxia-inducible factor (HIF)-mediated oxygen sensing, angiogenesis, and erythropoiesis. In contrast, major biological processes identified for proteomics signatures include 14-3-3 mediated sirtuin signaling, integrin-linked kinase (ILK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and integrin signaling. Comparing genetic and protein signatures, we identified 7 common genes/proteins (HBB/hemoglobin subunit beta, TF/serotransferrin, ANGPTL4/angiopoietin-related protein 4, CDC42/cell division control protein 42 homolog, GC/vitamin D-binding protein, IGFBP1/insulin-like growth factor-binding protein 1, and IGFBP2/insulin-like growth factor-binding protein 2) involved in crucial molecular functions like IGF-1 signaling, LXR/RXR activation, ferroptosis signaling, iron homeostasis signaling and regulation of cell cycle. Our combined multi-omics analysis identifies common molecular targets and pathways for human adaptation to high altitude. These observations further corroborate convergent positive selection of hypoxia-responsive molecular pathways in humans and advocate using multi-omics techniques for deciphering human adaptive responses to high altitude.
Assuntos
Altitude , Somatomedinas , Genômica , Humanos , Hipóxia/genética , Fosfatidilinositol 3-Quinases/genética , Proteômica , Seleção Genética , Somatomedinas/genéticaRESUMO
The insulin-like growth factor/insulin-like polypeptide (IGF/ILP) signaling is vital for growth, physiological metabolism, development, and reproduction. Insulin-like growth factor-binding protein (IGFBP) is involved in the insulin signaling pathway in both vertebrates and invertebrates and is critical for various physiology functions. Herein, we cloned and characterized the full-length cDNA of IGFBP-rp in the swimming crab, Portunus trituberculatus (PtIGFBP-rp). The deduced amino acid sequence of PtIGFBP-rp was found to contain three key domains (insulin-like binding (IB) domain, the kazale-type serine protease inhibitor (KAZAL) domain, and the immunoglobulin-like C2 (IGc2) domain). Results showed that PtIGFBP-rp shared the same expression pattern as P. trituberculatus insulin androgenic gland hormone (PtIAG) transcripts during the embryonic larval, juvenile crab stage and the androgenic gland (AG) developmental cycle. Moreover, PtIGFBP-rp transcripts were also present in high abundance in hepatopancreas, muscle, and androgenic glands. The regulatory relationship between PtIGFBP-rp and PtIAG was investigated by RNA interference and co-localization assays, which showed a co-localization relationship and feedback regulation between them. Bilateral eye stalk ablation (ESA) increased the expression of PtIGFBP-rp in the AG at 7 d after surgery. These results demonstrate the involvement of PtIGFBP-rp in the signaling regulatory network of IAG in P. trituberculatus.
Assuntos
Braquiúros , Somatomedinas , Androgênios/metabolismo , Animais , Braquiúros/genética , Braquiúros/metabolismo , Insulina/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Filogenia , Somatomedinas/genética , Somatomedinas/metabolismo , NataçãoRESUMO
Trimethyl bisphenol F (TMBPF) has recently been used as a bisphenol A substitute in polymer coatings for metal cans containing beverages or food. This study investigated whether TMBPF disrupts the endocrine system associated with thyroid hormones and growth hormones employing zebrafish embryos and larvae. After 14 days of exposure, body weight was significantly reduced when zebrafish were exposed to a TMBPF concentration greater than 50 µg/L. The triiodothyronine levels were significantly increased, while growth hormone levels were significantly decreased in larvae exposed to 5 µg/L TMBPF. The transcription of genes associated with thyroid hormone production (trα, tpo, tg, and nis), deiodination (deio2), growth hormone production (gh1, ghrh, and ghra), and insulin-like growth factor (igf2a, igf2b, igf2r, igfbp1a, igfbp1b, igfbp2a, igfbp2b, and igfbp5a) was significantly upregulated, whereas the transcription of genes association with thyrotropin-releasing hormone (trh and trhr1) was significantly downregulated. These results suggest that hyperthyroidism, decrease in growth hormone, and regulation of genes involved in the hypothalamus-pituitary-thyroid and growth hormone/insulin-like growth factor might be responsible for the observed growth inhibition in larvae exposed to TMBPF. The bioaccumulation of TMBPF and its effects on the endocrine system after chronic exposure requires further investigation.
Assuntos
Somatomedinas , Poluentes Químicos da Água , Animais , Compostos Benzidrílicos , Sistema Endócrino/metabolismo , Hormônio do Crescimento/metabolismo , Larva , Fenóis , Somatomedinas/genética , Somatomedinas/metabolismo , Glândula Tireoide , Hormônios Tireóideos/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismoRESUMO
OBJECTIVE: Phoenixin-20 (Pnx-20) is a bioactive peptide with endocrine-like actions in vertebrates. Recent studies suggest Pnx-20 promotes growth hormone/insulin-like growth factors (Gh/Igf) axis, an important endocrine regulator of growth in mammals and fish. DESIGN: In this research, we determined whether Pnx-20 affects the different members of the Igf family, its binding proteins and receptors (Igf-system) in zebrafish liver and muscle. RESULTS: In vivo administration of Pnx-20 downregulated igfs, igf receptors (igfrs) and igf binding protein (igfbp) 5 mRNA expression in the liver of male and female zebrafish at both 1 and 6 h post-intraperitoneal (IP) injection. Interestingly, this effect occurred at a relatively earlier timepoint in female zebrafish suggesting sex-specific differences in Pnx-20 action. Besides, either 6 or 24 h in vitro incubations with Pnx-20 downregulated the expression of all igfs, igfrs and igfbp5 mRNAs (except igf2a) analyzed in a zebrafish liver cell (ZFL) line. Moreover, siRNA-mediated knockdown of Pnx-20 upregulated all Igf-system mRNAs analyzed in ZFL cells. Together, these results (both in vivo and in vitro) revealed a general suppressive action for both endogenous and exogenous Pnx-20 on the hepatic Igf-system of zebrafish. In contrast, a general sex-specific upregulation of the Igf-system mRNAs analyzed was found in the muscle of Pnx-20 injected fish. Future research should explore the sex- and time-differences observed in the present study. CONCLUSIONS: Collectively, this research shows that Pnx-20 is a tissue-specific regulator of the liver (suppressor) and muscle (stimulant) Igf signaling in both male and female zebrafish.
Assuntos
Somatomedinas , Peixe-Zebra , Animais , Feminino , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/metabolismo , Masculino , Mamíferos/genética , Mamíferos/metabolismo , Músculos/metabolismo , Hormônios Peptídicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Somatomedina/metabolismo , Somatomedinas/genética , Somatomedinas/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
N6-methyladenosine (m6A) plays a critical role in the tumorigenesis of cervical cancer (CC). Here, we aimed to investigate the potential role of methyltransferase-like 3 (METTL3) in CC. Gene expression was determined via real-time quantitative polymerase chain reaction. Cellular functions were detected using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assays. The interactions among METTL3, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), and apoptotic chromatin condensation inducer 1 (ACIN1) were confirmed using the MeRIP and RIP assays. An in vivo assay was performed to verify the role of METTL3 in CC development. METTL3 is overexpressed in CC, and therefore, its knockdown inhibits the proliferation and migration of CC cells. Silencing METTL3 inhibits tumor growth in vivo. Moreover, a positive association was observed between METTL3 and ACIN1. METTL3 interacts with IGF2BP3 to promote the mRNA stability of ACIN1, the overexpression of which induces the aggressiveness of CC cells. METTL3 promotes ACIN1 mRNA stability to accelerate CC progression, implying that METTL3 is a promising biomarker in CC.
Assuntos
Somatomedinas , Neoplasias do Colo do Útero , Cromatina/genética , Feminino , Humanos , Metiltransferases/genética , Metiltransferases/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Estabilidade de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Somatomedinas/genética , Neoplasias do Colo do Útero/genéticaRESUMO
Water temperature alone can affect the growth, metabolic rates and physiological responses of aquatic organisms. Our earlier study reported that higher temperature affects cellular and hemato-biochemical responses in rohu, Labeo rohita. In this backdrop, the present study assessed the effect of higher acclimation temperature on the regulatory mechanisms of growth and stress responses of juvenile L. rohita acclimatized in three temperature conditions (30 °C, 33 °C, and 36 °C) for a period of 30 days. The relative expression of genes for growth hormone (GH), insulin-like growth factors (IGF-1 and IGF-2) and heat shock proteins (hsp70 and hsp90) were measured by real-time quantitative PCR. The results revealed that the highest acclimation temperature (36 °C) significantly decreased the weight gain (WG) and specific growth rate (SGR), and increased the feed conversion ratio (FCR) compared to 30 °C (control), while increased WG, SGR and lowered FCR were observed in fish reared at the intermediate temperature (33 °C) compared to 30 °C. Similarly, the GH gene expression in the pituitary was significantly decreased and increased at 36 °C and 33 °C, respectively as compared to 30 °C. A significantly lower expression of IGF-1 and IGF-2, and higher expression of hsp70 and hsp90 were observed in the liver of fish at 36 °C. The results of the present study indicate that although slightly elevated temperature promotes the growth of juvenile L. rohita, the higher acclimation temperature may induce stress response and impair growth performance by suppressing GH/IGF system.
Assuntos
Peso Corporal , Cyprinidae/metabolismo , Proteínas de Peixes/metabolismo , Hormônio do Crescimento/genética , Somatomedinas/metabolismo , Termotolerância , Animais , Cyprinidae/crescimento & desenvolvimento , Cyprinidae/fisiologia , Proteínas de Peixes/genética , Hormônio do Crescimento/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Somatomedinas/genéticaRESUMO
A customized PCR-array was used for the simultaneous gene expression of the Gh/Igf system and related markers of muscle growth, and lipid and energy metabolism during early life stages of gilthead sea bream (60-127 days posthatching). Also, transcriptional reprogramming by mild hypoxia was assessed in fingerling fish with different history trajectories on O2 availability during the same time window. In normoxic fish, the expression of almost all the genes in the array varied over time with a prompted liver and muscle tissue-specific differentiation, which also revealed temporal changes in the relative expression of markers of the full gilthead sea bream repertoire of Gh receptors, Igfs and Igf-binding proteins. Results supported a different contribution through development of ghr and igf subtypes on the type of action of GH via systemic or direct effects at the local tissue level. This was extensive to Igfbp1/2/4 and Igfbp3/5/6 clades that clearly evolved through development as hepatic and muscle Igfbp subtypes, respectively. This trade-off is however very plastic to cope changes in the environment, and ghr1 and igfbp1/3/4/5 emerged as hypoxic imprinting genes during critical early developmental windows leading to recognize individuals with different history trajectories of oxygen availability and metabolic capabilities later in life.
Assuntos
Perfilação da Expressão Gênica , Hormônio do Crescimento/genética , Hipóxia/genética , Dourada/genética , Somatomedinas/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento , Reação em Cadeia da Polimerase/métodosRESUMO
It has been well established that insulin-like growth factors (IGFs) mainly mediate long-term actions in cell fates, whereas insulin predominantly exerts its role on metabolic activity. Indeed, insulin mediates multiple anabolic biological activities in glucose and amino acid transport, lipid and protein synthesis, the induction of glycogen, the inhibition of gluconeogenesis, lipolysis, and protein degradation. The interactions and differences between insulin receptor signaling and IGF-I receptor signaling in the metabolism and the cell fates are quite complicated. Because of the overlapping actions of IGF-I singling with insulin signaling, it has been difficult to distinguish the role of both signaling mechanisms on the metabolism. Furthermore, comprehensive information on the IGF-I function in respective tissues remains insufficient. Therefore, we need to clarify the precise roles of IGF-I signaling on the metabolism separate from those of insulin signaling. This review focuses on the metabolic roles of IGFs in the respective tissues, especially in terms of comparison with those of insulin, by overviewing the metabolic phenotypes of tissue-specific IGF-I and insulin receptor knockout mice, as well as those in mice treated with the dual insulin receptor/IGF-I receptor inhibitor OSI-906.
Assuntos
Metabolismo Energético , Somatomedinas/metabolismo , Animais , Regulação da Expressão Gênica , Humanos , Insulina/metabolismo , Camundongos , Especificidade de Órgãos , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo , Transdução de Sinais , Somatomedinas/genéticaRESUMO
Many insect species have several genes coding for insulin-related peptides (IRPs), but so far only a single IRP gene has been identified in migratory locusts. Here, we report and characterize two other genes coding for peptides that are related to insulin, namely gonadulin and arthropod insulin-like growth factor (aIGF); peptides postulated to be orthologs of Drosophila melanogaster insulin-like peptides 8 and 6 respectively. In Locusta migratoria the aIGF transcript is expressed in multiple tissues as was previously reported for IRP in both L. migratoria and Schistocerca gregaria, but there are significant differences in expression patterns between the two species. The gonadulin transcript, however, seems specific to the ovary, whereas its putative receptor transcript is expressed most abundantly in the ovary, fat body and the central nervous system. Since the central nervous system-fat body-ovary axis is essential for successful reproduction, we studied the influence of gonadulin on vitellogenesis and oocyte growth. A reduction in the gonadulin transcript (via RNA interference) led to a significant reduction in vitellogenin mRNA levels in the fat body and a strong oocyte growth inhibition, thus suggesting an important role for gonadulin in reproduction in this species.
Assuntos
Proteínas de Insetos/genética , Locusta migratoria/genética , Peptídeos/genética , Somatomedinas/genética , Animais , Corpo Adiposo/metabolismo , Feminino , Proteínas de Insetos/fisiologia , Locusta migratoria/fisiologia , Masculino , Oócitos/metabolismo , Ovário/metabolismo , Peptídeos/fisiologia , Reprodução/genética , Somatomedinas/fisiologia , Testículo/metabolismo , Transcriptoma , Vitelogeninas/genéticaRESUMO
M2like tumourassociated macrophages (TAMs) have been demonstrated to promote the growth of anaplastic thyroid carcinoma (ATC). However, the underlying mechanism of M2like TAMs in ATC remains unclear. Thus, in the present study, the role and mechanism of M2like TAMs in ATC were investigated. M2like TAMs were induced by treatment with PMA, plus IL4 and IL13, and identified by flow cytometry. Transwell and sphere formation assays were applied to assess the invasion and stemness of ATC cells. The expression levels of insulinlike growth factor (IGF)1 and IGF2 were examined by ELISA and reverse transcriptionquantitative PCR. Proteins related to the epithelialmesenchymal transition (EMT), stemness and the PI3K/AKT/mTOR pathway were examined via western blotting. Immunohistochemistry (IHC) was used to detect the expression of the M2like TAM markers CD68 and CD206 in ATC tissues and thyroid adenoma tissues. It was found that treatment with PMA plus IL4 and IL13 successfully induced M2like TAMs. Following coculture with M2like TAMs, the invasive ability and stemness of ATC cells were significantly increased. The expression levels of the EMTrelated markers Ncadherin and Vimentin, the stemnessrelated markers Oct4, Sox2 and CD133, and the insulin receptor (IR)A/IGF1 receptor (IGF1R) were markedly upregulated, whereas Ecadherin expression was significantly decreased. In addition, the production of IGF1 and IGF2 was significantly increased. Of note, exogenous IGF1/IGF2 promoted the invasion and stemness of C643 cells, whereas blocking IGF1 and IGF2 inhibited metastasis and stemness by repressing IRA/IGF1Rmediated PI3K/AKT/mTOR signalling in the coculture system. IHC results showed that the expression of CD68 and CD206 was obviously increased in ATC tissues. To conclude, M2like TAMs accelerated the metastasis and increased the stemness of ATC cells, and the underlying mechanism may be related to the section of IGF by M2like TAMs, which activates the IRA/IGF1Rmediated PI3K/AKT/mTOR signalling pathway.
Assuntos
Células-Tronco Neoplásicas , Transdução de Sinais , Somatomedinas/metabolismo , Carcinoma Anaplásico da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Macrófagos Associados a Tumor/metabolismo , Adulto , Idoso , Anticorpos Neutralizantes/farmacologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Linhagem Celular , Cromonas/farmacologia , Feminino , Humanos , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like II/antagonistas & inibidores , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like II/farmacologia , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Morfolinas/farmacologia , Invasividade Neoplásica/imunologia , Metástase Neoplásica/imunologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Insulina/antagonistas & inibidores , Receptor de Insulina/metabolismo , Receptores Imunológicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Somatomedinas/genética , Serina-Treonina Quinases TOR/metabolismo , Carcinoma Anaplásico da Tireoide/imunologia , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/patologia , Adulto JovemRESUMO
Effects of nutrition on insulin-like growth factor-I (IGF-I), IGF binding proteins (IGFBP), and insulin in plasma and dominant follicles were evaluated at day 72 and 56 (Exp. 1, nâ¯=â¯12 and Exp. 2, n = 28, respectively) postpartum in anovulatory primiparous beef cows. Cows were stratified based on body condition score at calving and randomly assigned to nutritional treatments: maintain (M), 2.27â¯kg of a 40 % CP supplement per day and ad libitum hay; or gain (G), ad libitum access to a 50 % concentrate diet and ad libitum hay. Blood samples were collected twice weekly starting 30 days postpartum. Ovarian follicles were evaluated using ultrasonography commencing 42 (Exp. 1) or 30 (Exp. 2) days postpartum. Body weight and condition score were greater (P < 0.05) for cows of G than M groups and postpartum interval to luteal function was longer for cows of the M than G group. Insulin and IGF-I concentrations in follicular fluid (FF) and plasma were greater (P < 0.05) for cows of the G than M group at follicular aspiration. Plasma and FF IGFBP4 and IGFBP5 concentrations were greater (Pâ¯<⯠0.05) in Exp. 2, and IGFBP5 was greater in Exp. 1 for cows of the G than M group. Treatment did not affect FF steroid concentrations or granulosal cell CYP19A1, PAPPA, IGFBP4, and IGFBP5 mRNA abundance. These results indicate concentrations of IGF-I, insulin, IGFBP4, and IGFBP5 in FF and plasma are affected by nutritional intake and may be related to follicular function.