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[This retracts the article on p. 55 in vol. 16, PMID: 38464818.].
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BACKGROUND: Colorectal polyps (CPs) are frequently occurring abnormal growths in the colorectum, and are a primary precursor of colorectal cancer (CRC). The triglyceride-glucose (TyG) index is a novel marker that assesses metabolic health and insulin resistance, and has been linked to gastrointestinal cancers. AIM: To investigate the potential association between the TyG index and CPs, as the relation between them has not been documented. METHODS: A total of 2537 persons undergoing a routine health physical examination and colonoscopy at The First People's Hospital of Kunshan, Jiangsu Province, China, between January 2020 and December 2022 were included in this retrospective cross-sectional study. After excluding individuals who did not meet the eligibility criteria, descriptive statistics were used to compare characteristics between patients with and without CPs. Logistic regression analyses were conducted to determine the associations between the TyG index and the prevalence of CPs. The TyG index was calculated using the following formula: Ln [triglyceride (mg/dL) × glucose (mg/dL)/2]. The presence and types of CPs was determined based on data from colonoscopy reports and pathology reports. RESULTS: A nonlinear relation between the TyG index and the prevalence of CPs was identified, and exhibited a curvilinear pattern with a cut-off point of 2.31. A significant association was observed before the turning point, with an odds ratio (95% confidence interval) of 1.70 (1.40, 2.06), P < 0.0001. However, the association between the TyG index and CPs was not significant after the cut-off point, with an odds ratio (95% confidence interval) of 0.57 (0.27, 1.23), P = 0.1521. CONCLUSION: Our study revealed a curvilinear association between the TyG index and CPs in Chinese individuals, suggesting its potential utility in developing colonoscopy screening strategies for preventing CRC.
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PURPOSE: PABPN1 acts as a modulator of poly(A) tail length and alternative polyadenylation. This research was aimed to explore the role of PABPN1 in colorectal cancer (CRC). METHODS: Public databases were performed to analyze expression, location, roles of prognosis and tumor immunity and interaction with RNAs and proteins of PABPN1. To investigate PABPN1 expression in tissues, 78 CRC specimens were collected to conduct IHC, and 30 pairs of frozen CRC and corresponding adjacent normal tissues were used to conduct qRT-PCR and WB. In addition, in vitro experiments were then carried out to identify the role of PABPN1 in CRC. RESULTS: Compared with normal tissues, PABPN1 expression was significant higher in CRC. Its high level predicted poor outcome of CRC. Th1 and Treg had significant negative relationships not only with PABPN1 expression, but also with six molecules interacting with PABPN1, including IFT172, KIAA0895L, RECQL4, WDR6, PABPC1 and NCBP1. In addition, PABPN1 had negative relationships with quite a few immune markers, such as CSF1R, IL-10, CCL2 and so on. In cellular experiments, silencing PABPN1 inhibited proliferation and promoted apoptosis in HCT-116 CRC cells. CONCLUSION: In summary, PABPN1 might become a novel biomarker and correlate with tumor immunity in CRC.
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Neoplasias Colorretais , RNA , Humanos , RNA Mensageiro , Células HCT116 , Biomarcadores , Neoplasias Colorretais/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Proteína I de Ligação a Poli(A) , Proteínas do Citoesqueleto/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
Objective: This research was aimed to preliminarily explore the clinical roles and potential molecular mechanisms of MIR99AHG and its significant transcripts in breast cancer (BRCA). Methods: Public databases were utilized to analyze the expression and prognostic roles of MIR99AHG and its transcripts. Relationships between MIR99AHG expression and immune cells infiltration were analyzed in Xiantao platform. In addition, co-expressed genes and interacting proteins of MIR99AHG were predicted. CancerSEA analyzed its relationship with functional states. Next, CNV status, DNA methylation, interacting transcription factors (TFs) and ceRNA network were analyzed to explore its possible mechanisms. Then, RNA ISH and FISH assays were used to detect its expression and location in BRCA tissues and cell lines, respectively. Finally, qRT-PCR was utilized to investigate MIR99AHG expression in cell lines. Results: Compared with the corresponding normal tissues, MIR99AHG expression levels were lower in all BRCA subtypes, and luminal B's was the lowest one. And MIR99AHG expression was negatively related to the tumor stage. In addition, 4 transcripts (ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5) of MIR99AHG showed significant differences in the expression. Databases also suggested that the high MIR99AHG expression levels indicated good prognosis, especially in patients without lymph node metastasis. Xiantao found that MIR99AHG was positively related to 17 immune cells and negatively linked with 2 immune cells. CancerSEA analysis showed no relationships between MIR99AHG and functional states. From GEPIA and BCIP databases, 19 co-expressed genes were highly related to these four significant transcripts of MIR99AHG. StarBase, RNAct and HDOCK showed that several tumor-associated proteins, including U2AF65, hnRNPC, AEBP2, CHIC1 and so on, might interact with MIR99AHG. Genetically, BRCA had a higher proportion of MIR99AHG CNV loss than CNV gain, and the high level of DNA methylation indicated a good prognosis. Furthermore, 19 TFs were predicted to combine with the promoter of MIR99AHG. Then, we screened out 10 miRNAs potentially interacting with the significant transcripts of MIR99AHG, and five were significantly increased in breast tumors compared to normal tissues, including miR-194-5p, miR-320 b and so on, which could combine 14 mRNAs. Through ISH and FISH assays, we verified that MIR99AHG was down-regulated in BRCA samples and cell lines in comparison to non-tumor tissues and mammary epithelial cell line (MCF10A), and MIR99AHG was located both in cytoplasm and nucleus. qRT-PCR assay also showed the lower expression of MIR99AHG in breast cancer cells than that in MCF10A. Conclusion: These results indicate that MIR99AHG can be a favorable prognostic indicator for BRCA. ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5 are significant transcripts and their down-regulation may play crucial roles in the progression of BRCA.