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Objective: Recent studies have demonstrated that the Dietary Inflammatory Index (DII) is relevant to abnormal gut health. However, there is a lack of studies that have explicitly explored the link between fecal incontinence (FI) and DII. The current study aims to explore the relationship between DII and FI. Methods: The cross-sectional study enrolled a total of 11,747 participants aged 20-85 from NHANES 2005-2010. Weighted logistic regression was conducted to evaluate the relationship between DII and FI, and restricted cubic spline (RCS) was employed to assess the dose-response relationship between DII and FI. Subgroup analyses were performed according to age, gender, race, and BMI. Result: DII levels were found to be significantly higher in patients with FI than in the normal population (p = 0.016). After adjusting for all covariates, DII was found to be significantly correlated with FI (model 2: Q4 vs. Q1, OR = 1.49, 95% CI: 1.04-2.14, p = 0.032, p for trend = 0.039). The dose-response curve revealed that there was no non-linear correlation between DII and FI (p-non-linear = 0.234). Subsequent subgroup analyses uncovered that DII was notably associated with FI in the old (Q4 vs. Q1, OR = 1.84, 95% CI: 1.07-3.18, p = 0.030), female (Q4 vs. Q1: OR = 2.02, 95% CI: 1.23-3.33, p = 0.008), non-Hispanic white (Q4 vs. Q1: OR = 1.70, 95% CI: 1.12-2.59, p = 0.015) populations. Conclusion: DII was positively associated with FI, particularly among old, female and non-Hispanic white individuals. Decreasing daily dietary inflammatory levels may be an effective tactic to prevent FI, but the precise mechanisms need to be further investigated.
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Sorting nexin 16 (SNX16), a pivotal sorting nexin, emerges in tumor progression complexity, fueling research interest. However, SNX16's biological impact and molecular underpinnings in hepatocellular carcinoma (HCC) remain elusive. This study probes SNX16's function, clinical relevance via mRNA, and protein expression in HCC. Overexpression/knockdown assays of SNX16 were employed to elucidate impacts on HCC cell invasion, proliferation, and EMT. Additionally, the study delved into SNX16's regulation of the EGFR-AKT signaling cascade mechanism. SNX16 overexpression in HCC correlates with poor patient survival; enhancing proliferation, migration, invasion, and tumorigenicity, while SNX16 knockdown suppresses these processes. SNX16 downregulation curbs phospho-EGFR, dampening AKT signaling. EGFR suppression counters SNX16-overexpression-induced HCC proliferation, motility, and invasiveness. Our findings delineate SNX16's regulatory role in HCC, implicating it as a prospective therapeutic target.
Asunto(s)
Carcinoma Hepatocelular , Movimiento Celular , Proliferación Celular , Receptores ErbB , Neoplasias Hepáticas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Nexinas de Clasificación , Animales , Humanos , Ratones , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Línea Celular Tumoral , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Receptores ErbB/metabolismo , Receptores ErbB/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genéticaRESUMEN
OBJECTIVE: Krüppel-like factor 4 (KLF4) has been demonstrated to exert a pro-carcinogenic effect in solid tissues. However, the precise biological function and underlying mechanisms in colorectal cancer (CRC) remains elucidated. AIMS: To investigate whether KLF4 participates in the proliferation and invasion of CRC. METHODS: The expression of KLF4 was investigated using immunohistochemistry and immunoblotting. The clinical significance of KLF4 was evaluated. Furthermore, the effect of inhibiting or overexpressing KLF4 on tumor was examined. Immunoblotting and qPCR were used to detect Epithelial-mesenchymal transition-related proteins levels. Additionally, the molecular function of KLF4 is related to the STAT3 signaling pathway and was determined through JASPAR, GSEA analysis, and in vitro experiments. RESULTS: KLF4 exhibits down-regulated expression in CRC and is part of the vessel invasion, TNM stage, and worse prognosis. In vitro studies have shown that KLF4 promotes cellular proliferation and invasion, as well as EMT processes. Xenograft tumor models confirmed the oncogenic role of KLF4 in nude mice. Furthermore, GSEA and JASPAR databases analysis reveal that the binding of KLF4 to the signal transducer and activator of transcription 3 (STAT3) promoter site induces activation of p-STAT3 signaling. Subsequent targeting of STAT3 confirmed its pivotal role in mediating the oncogenic effects exerted by KLF4. CONCLUSION: The study suggests that KLF4 activates STAT3 signaling, inducing epithelial-mesenchymal transition, thereby promoting CRC progression.
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Proliferación Celular , Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel , Ratones Desnudos , Factor de Transcripción STAT3 , Factor 4 Similar a Kruppel/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Animales , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Masculino , Femenino , Ratones , Transducción de Señal , Persona de Mediana Edad , Invasividad Neoplásica , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Ratones Endogámicos BALB CRESUMEN
OBJECTIVE: The function of Kruppel-like factor 3 (KLF3) remains largely unexplored in colorectal cancer (CRC). METHODS: KLF3 expression in CRC was assessed through qPCR, western blotting, immunohistochemical assays, and The Cancer Genome Atlas (TCGA) database. The tumor-promoting capacity of KLF3 was explored by performing in vitro functional experiments using CRC cells. A subcutaneous nude mouse tumor assay was employed to evaluate tumor growth. To further elucidate the interaction between KLF3 and other factors, luciferase reporter assay, agarose gel electrophoresis, and ChIP analysis were performed. RESULTS: KLF3 was downregulated in CRC tissue and cells. Silencing of KLF3 increased the potential of CRC cells for proliferation, migration, and invasion, while its activation decreased these processes. Downregulated KLF3 was associated with accelerated tumor growth in vivo. Mechanistically, KLF3 was discovered to target the promoter sequence of WNT1. Consequently, the diminished expression of KLF3 led to the buildup of WNT1 and the WNT/ß-catenin pathway activation, consequently stimulating the progression of CRC. CONCLUSIONS: This investigation suggests that the involvement of KLF3/WNT1 regulatory pathway contributes to the progression of CRC, thereby emphasizing its promise as an important focus for future therapies aimed at treating CRC.
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Neoplasias Colorrectales , Factores de Transcripción , Ratones , Animales , Factores de Transcripción/metabolismo , beta Catenina/metabolismo , Proliferación Celular/genética , Regiones Promotoras Genéticas , Neoplasias Colorrectales/patología , Vía de Señalización Wnt/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genéticaRESUMEN
BACKGROUND: Colorectal cancer (CRC) is a prevalent type of gastrointestinal cancer, and its poor prognosis is mainly attributed to the occurrence of invasion and metastasis. CYP1B1-AS1, as non-coding RNA, plays an important role in tumorigenesis and progression. However, the mechanism by which CYP1B1-AS1 acts in CRC is not yet understood. AIMS: The objective of this study was to investigate how CYP1B1-AS1 contributes to the development of CRC, and provide a base for CRC diagnosis and treatment. METHODS: RT-qPCR was used to detect the expression level of CYP1B1-AS1 in CRC and adjacent tissues. CCK-8, Edu, scratch healing, and transwell experiments were used to detect the changes of proliferation, migration, and invasion ability of CRC cells after overexpression or knockdown of CYP1B1-AS1 respectively. The RNA binding protein NOP58 combined with CYP1B1-AS1 was verified by RIP and RNA Pull-down experiments. Functional recovery experiments validated the interaction between CYP1B1-AS1 and NOP58 in CRC cells. The changes of EMT-related proteins were detected by Western blot, and the half-life of transcription factor SNAIL mRNA were detected by RT-qPCR after overexpression or knockdown of NOP58. RESULTS: CYP1B1-AS1 was found to be significantly downregulated in CRC compared to adjacent noncancerous tissues. Experiments conducted in vitro and in vivo confirmed that upregulation of CYP1B1-AS1 significantly inhibited the proliferation, migration, and invasion of CRC cells. In addition, CYP1B1-AS1 can directly bind to NOP58 and negatively regulate NOP58. The effect of overexpression CYP1B1-AS1 was reversed by NOP58 overexpression. NOP58 regulates the EMT process of CRC cells by affecting the stability of EMT-related transcription factor SNAIL mRNA, and then affects the progress of CRC. CONCLUSION: This research proves that CYP1B1-AS1 can inhibit the occurrence of EMT in CRC by binding with NOP58, thus delaying the progress of CRC. This finding indicates that CYP1B1-AS1 may be a novel biomarker to improve the diagnosis and treatment of CRC.
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Neoplasias Colorrectales , MicroARNs , ARN Largo no Codificante , Humanos , Línea Celular Tumoral , MicroARNs/genética , Factores de Transcripción/genética , Neoplasias Colorrectales/patología , ARN Mensajero , Proliferación Celular/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Proteínas Nucleares/genética , Ribonucleoproteínas Nucleolares Pequeñas/genética , Ribonucleoproteínas Nucleolares Pequeñas/metabolismoRESUMEN
BACKGROUND: Previous studies indicate that the splicing process, regulated by the cellular machinery of tumors (spliceosome), undergoes alterations, leading to oncogenic splicing events associated with the progression of tumors towards aggressiveness. However, the role of serine/arginine-rich splicing factor 7 (SRSF7) in hepatocellular carcinoma (HCC) and the tumor microenvironment (TME) remains unclear. METHODS: This study was aimed to explore the role and clinical significance of SRSF7 in HCC. By conducting functional analysis and gene set enrichment analysis, it was discovered that SRSF7 contributes to multiple pathways associated with immune response and tumor advancement. Further experiments verified that silencing of SRSF7 obviously inhibits progression of HCC. RESULTS: Aberrant expression of SRSF7, which were referred as an independent prognostic risk factor, effectively predicts the prognosis of patients with HCC. Functional and gene enrichment analyses revealed that SRSF7 is linked with multiple immune and tumor progression-related pathways, including the B cell receptor signaling pathway, positive regulation of leukocyte and immunoglobulin receptor binding cell activation, nuclear division, membrane invagination, cell cycle, as well as mTOR signaling pathway. Furthermore, increased SRSF7 expression was associated with tumor-infiltrating inflammatory cells (CD4+, monocytes/macrophages, CD8 + and endothelial). Additionally, multiple immune checkpoint genes were markedly positively related to SRSF7. The efficiency of SRSF7 in predicting immunomodulator and chemokine responses were also assessed in microenvironment. Moreover, in vitro analyses demonstrated that knockdown of SRSF7 suppressed the malignant evolution of HCC possibly by deactivating the PI3K/AKT/mTOR signaling. CONCLUSION: The role of SRSF7 in the tumor microenvironment has been successfully assessed. It may be a valid bio-index for predicting the HCC prognosis, thereby guiding individualized immunotherapy for cancer.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Fosfatidilinositol 3-Quinasas/genética , Pronóstico , Neoplasias Hepáticas/genética , Serina-Treonina Quinasas TOR , Biomarcadores , Microambiente Tumoral/genética , Factores de Empalme Serina-Arginina/genéticaRESUMEN
BACKGROUND: Emerging evidence showed that FAT10 is a vital regulator of tumor occurrence and development. The molecular mechanisms underlying the specific role of FAT10 in colorectal cancer (CRC) are not yet known. AIMS: To investigate whether FAT10 participates in the proliferation, invasion and metastasis of CRC. METHODS: This study investigated the function and clinical significance of FAT10 protein expression in CRC. Furthermore, over-expression and knockdown experiments of FAT10 were developed to explore their effects on CRC cell migration and proliferation. Moreover, a molecular mechanism of FAT10 regulate calpain small subunit 1(Capn4) was explored. RESULTS: In this research, the FAT10 expression level was elevated in CRC tissues compared to corresponding normal tissues. In addition, the elevated FAT10 expression level is significantly linked to advanced clinical stage and poor CRC prognosis. Furthermore, a very high expression of FAT10 was observed in CRC cells, and FAT10 overexpression significantly enhanced the in vivo proliferation, invasion, and metastasis of the cells, whereas knockdown of FAT10 inhibited all these cellular factors in both in vivo and in vitro environments. Moreover, the outcomes of this study suggested that FAT10 enhances colorectal cancer progression through enhancement of Capn4 expression, leading to the progression of various human tumors, as reported by previous research. The mechanism via which FAT10 promotes CRC cells proliferation, invasion, and metastasis involves modification of the ubiquitination and degradation processes of Capn4. CONCLUSION: FAT10 is a vital regulator of the tumorigenesis and advancement of CRC, thus serving as a promising pharmaceutical target for treating CRC patients.
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Carcinogénesis , Neoplasias Colorrectales , Humanos , Línea Celular Tumoral , Proliferación Celular/fisiología , Neoplasias Colorrectales/genética , Ubiquitinación , Ubiquitinas/genética , Ubiquitinas/metabolismo , Movimiento Celular , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Homeobox B9 (HOXB9) is one of the HOX family of transcription factors that are essential for cancer development and embryonic growth. However, the clinical importance and biological involvement of HOXB9 in colon cancer (CC) are not adequately understood. AIMS: To investigate whether HOXB9 participates in the proliferation, invasion, and migration of CC. METHODS: This study investigated the function and clinical significance of HOXB9 mRNA and protein expression in CC. Furthermore, overexpression and knockdown experiments of HOXB9 were developed to explore their effects on CC cell transwell and proliferation. Moreover, a molecular mechanism of HOXB9 regulate serine/arginine-rich splicing factor 3 (SRSF3) was explored. RESULTS: HOXB9 expression was higher in CC cells and tissues at both the mRNA and protein levels. Poor survival in CC patients was significantly connected with high HOXB9 expression, which was also strongly associated with the TNM stage and lymph node metastases. Furthermore, in vitro CC cell proliferation, transwell were markedly aided by HOXB9 overexpression. Contrarily, HOXB9 knockdown had the reverse result and inhibited the formation of xenograft tumors in naked mice. Gene set enrichment analysis (GSEA) revealed a correlation between high HOXB9 expression and spliceosomes. JASPAR and GEPIA2.0, in addition to CHIP and dual-luciferase reporting assays, confirmed that HOXB9 targets the promoter of SRSF3 to enhance its expression. We also found that SRSF3 knockdown eliminated HOXB9 from cell proliferation and transwell. CONCLUSION: We characterized the function and mechanism of HOXB9 in regulating colon cancer growth, suggesting a novel molecular approach for colon cancer-targeted therapy.
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Neoplasias del Colon , Genes Homeobox , Humanos , Animales , Ratones , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/genética , Proliferación Celular , ARN Mensajero , Regulación Neoplásica de la Expresión Génica , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismoRESUMEN
BACKGROUND: The survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with hepatectomy for hepatocellular carcinoma (HCC) after hepatectomy remains controversial. We aimed to investigate the survival efficacy of adjuvant TACE after hepatectomy for HCC. METHODS: 1491 patients with HCC who underwent hepatectomy between January 2018 and September 2021 at four medical centers in China were retrospectively analyzed, including 782 patients who received adjuvant TACE and 709 patients who did not receive adjuvant TACE. Propensity score matching (PSM) (1:1) was performed to minimize selection bias, which balanced the clinical characteristics of the two groups. RESULTS: A total of 1254 patients were enrolled after PSM, including 627 patients who received adjuvant TACE and 627 patients who did not receive adjuvant TACE. Patients who received adjuvant TACE had higher disease-free survival (DFS, 1- ,2-, and 3-year: 78%-68%-62% vs. 69%-57%-50%, p < 0.001) and overall survival (OS, 1- ,2-, and 3-year: 96%-88%-80% vs. 90%-77%-66%, p < 0.001) than those who did not receive adjuvant TACE (Median DFS was 39 months). Among the different levels of risk factors affecting prognosis [AFP, Lymphocyte-to-monocyte ratio, Maximum tumor diameter, Number of tumors, Child-Pugh classification, Liver cirrhosis, Vascular invasion (imaging), Microvascular invasion, Satellite nodules, Differentiation, Chinese liver cancer stage II-IIIa], the majority of patients who received adjuvant TACE had higher DFS or OS than those who did not receive adjuvant TACE. More patients who received adjuvant TACE accepted subsequent antitumor therapy such as liver transplantation, re-hepatectomy and local ablation after tumor recurrence, while more patients who did not receive adjuvant TACE accepted subsequent antitumor therapy with TACE after tumor recurrence (All p < 0.05). CONCLUSIONS: Adjuvant TACE may be a potential way to monitor early tumor recurrence and improve postoperative survival in patients with HCC.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Hepatectomía , Recurrencia Local de Neoplasia/patología , Puntaje de Propensión , Estudios Retrospectivos , Quimioembolización Terapéutica/métodos , Pronóstico , Adyuvantes Inmunológicos , Resultado del TratamientoRESUMEN
Osteoarthritis (OA) is a worldwide epidemic and debilitating disease. It is urgent to explore the potential molecular mechanisms of OA which has crucial roles in the treatment strategy. As a post-translational modification, sialylation mediates the progression of OA. In current study, differential expression of sialyltransferases (STs) in normal and OA cartilage tissues is detected. The ST3GAL4 expression is significantly increased and positively associated with modified Mankin's score in OA tissue. Alteration of ST3GAL4 respectively mediates the degradation of extracellular mechanisms (ECM), apoptosis and proliferation in chondrocytes. Additionally, miR-193b is identified as a direct regulatory target of ST3GAL4. Functional analysis shows that modulation of ST3GAL4 could be reversed by miR-193b. Over-expression ST3GAL4 modifies CD44 sialylation. Finally, sialylated CD44 reduces the binding capacity to lubricin and mediates the activity of the NF-кB pathway. Collectively, these researches indicate that miR-193b/ST3GAL4 axis impacts OA progression by regulating CD44 sialylation via NF-кB pathway. Our researches propose a precise molecular mechanism and provide a prospective therapeutic target in OA.
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Receptores de Hialuranos/metabolismo , MicroARNs/fisiología , FN-kappa B/metabolismo , Osteoartritis/metabolismo , Sialiltransferasas/metabolismo , Adulto , Animales , Estudios de Casos y Controles , Células Cultivadas , Condrocitos , Humanos , Ratas Sprague-DawleyRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
Osteoarthritis (OA) is a joint disease that causes great pain to patients and imposes a tremendous burden on the world's medical resources. Regulatory noncoding RNAs, including circular RNAs (circRNAs) and microRNAs (miRNAs), play an important role in OA progression. Here, we identified differential expression of transcription factor LEF1 that increased circRNA circRNF121 levels in normal and OA cartilage tissues. The expression of LEF1 and circRNF121 was positively associated with Mankin's scores. Alteration of circRNF121 mediated the degradation of extracellular mechanisms (ECM), apoptosis, and proliferation of chondrocytes. MiR-665 was identified as a direct regulatory target of circRNF121 and MYD88. Functional analysis showed that circRNF121 and MYD88 modulated ECM degradation, apoptosis, and proliferation of chondrocytes, which could be reversed by miR-665. MYD88 regulated the activity of the NF-кB signaling pathway by circRNF121 via sponging miR-665. Collectively, these data indicated that LEF1 impacted OA progression by modulating the circRNF121/miR-665/MYD88 axis via NF-кB pathway. Our research proposed a new molecular mechanism for the development of OA, and provided a prospective therapeutic target for OA.