BACKGROUND Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)plays critical roles in the genesis and development of human cancers.AIM To investigate the clinical significance and role...BACKGROUND Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)plays critical roles in the genesis and development of human cancers.AIM To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.METHODS Expression levels of IGF2BP1 and microRNA-494(miR-494)were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot.The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed.The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo.Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the posttranscriptional regulation of IGF2BP1 by miR-494.RESULTS We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients.We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway.Mechanistically,we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer.Furthermore,we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.CONCLUSION Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.展开更多
MicroRNA-494(miR-494)has emerged as a potential diagnostic biomarker for cancer detection,but conflicting reports have led to uncertainty regarding its clinical utility.This study aims to address these discrepancies b...MicroRNA-494(miR-494)has emerged as a potential diagnostic biomarker for cancer detection,but conflicting reports have led to uncertainty regarding its clinical utility.This study aims to address these discrepancies by conducting a comprehensive metaanalysis of miR-494 diagnostic performance across various cancer types.A comprehensive literature search was performed across multiple databases,including PubMed,Web of Science,Wanfang databases,and CNKI(China National Knowledge Infrastructure),with a cutoff date of April 23,2024.Eligible studies were identified using predefined inclusion criteria and various search strategies to ensure a thorough coverage of the available evidence.To evaluate the diagnostic performance of miR-494 in cancer detection,relevant measures such as sensitivity,specificity,and other diagnostic accuracy indicators were extracted from the included studies.These data were synthesized using bivariate meta-analysis models to generate pooled estimates of miR-494 diagnostic performance.All statistical analyses were conducted using the STATA 16.0 software.This meta-analysis pooled data from 8 studies,comprising a total of 647 cancer cases and 407 healthy controls.The aggregated diagnostic performance of miR-494 was as follows:a sensitivity of 0.67(95%confidence interval[CI],0.52–0.80),a specificity of 0.85(95%CI,0.77–0.91),and an area under the curve of 0.86(95%CI,0.82–0.88),indicating good overall diagnostic accuracy.The diagnostic odds ratio(DOR)was 12.11(95%CI,7–21),suggesting that miR-494 has strong discriminatory power in distinguishing cancer patients from healthy individuals.The positive likelihood ratio of 4.62(95%CI,3.1–6.8)and negative likelihood ratio of 0.38(95%CI,0.26–0.56)further support the diagnostic utility of miR-494.Deeks’funnel plot asymmetry test was employed to assess potential publication bias,yielding a P value of 0.50,which suggests the absence of significant bias in the included studies.The meta-analysis results suggest that miR-494 exhibits promising diagnostic performance in detecting cancer,with moderate accuracy.The pooled sensitivity,specificity,and high area under the receiver operating characteristic curve highlight its potential as a cancer biomarker,indicating its utility in early detection and accurate diagnosis.展开更多
基金Supported by the National Natural Science Foundation of China,No.61802350
文摘BACKGROUND Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)plays critical roles in the genesis and development of human cancers.AIM To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.METHODS Expression levels of IGF2BP1 and microRNA-494(miR-494)were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot.The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed.The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo.Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the posttranscriptional regulation of IGF2BP1 by miR-494.RESULTS We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients.We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway.Mechanistically,we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer.Furthermore,we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.CONCLUSION Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.
基金supported by grants fromthe National Natural Science Foundation of China(no.82272961)Guangdong Basic and Applied Basic Research Foundation(no.2022A1515011353)the ShenzhenMunicipal Commission of Science and Technology Innovation(no.JCYJ20220530150814033).
文摘MicroRNA-494(miR-494)has emerged as a potential diagnostic biomarker for cancer detection,but conflicting reports have led to uncertainty regarding its clinical utility.This study aims to address these discrepancies by conducting a comprehensive metaanalysis of miR-494 diagnostic performance across various cancer types.A comprehensive literature search was performed across multiple databases,including PubMed,Web of Science,Wanfang databases,and CNKI(China National Knowledge Infrastructure),with a cutoff date of April 23,2024.Eligible studies were identified using predefined inclusion criteria and various search strategies to ensure a thorough coverage of the available evidence.To evaluate the diagnostic performance of miR-494 in cancer detection,relevant measures such as sensitivity,specificity,and other diagnostic accuracy indicators were extracted from the included studies.These data were synthesized using bivariate meta-analysis models to generate pooled estimates of miR-494 diagnostic performance.All statistical analyses were conducted using the STATA 16.0 software.This meta-analysis pooled data from 8 studies,comprising a total of 647 cancer cases and 407 healthy controls.The aggregated diagnostic performance of miR-494 was as follows:a sensitivity of 0.67(95%confidence interval[CI],0.52–0.80),a specificity of 0.85(95%CI,0.77–0.91),and an area under the curve of 0.86(95%CI,0.82–0.88),indicating good overall diagnostic accuracy.The diagnostic odds ratio(DOR)was 12.11(95%CI,7–21),suggesting that miR-494 has strong discriminatory power in distinguishing cancer patients from healthy individuals.The positive likelihood ratio of 4.62(95%CI,3.1–6.8)and negative likelihood ratio of 0.38(95%CI,0.26–0.56)further support the diagnostic utility of miR-494.Deeks’funnel plot asymmetry test was employed to assess potential publication bias,yielding a P value of 0.50,which suggests the absence of significant bias in the included studies.The meta-analysis results suggest that miR-494 exhibits promising diagnostic performance in detecting cancer,with moderate accuracy.The pooled sensitivity,specificity,and high area under the receiver operating characteristic curve highlight its potential as a cancer biomarker,indicating its utility in early detection and accurate diagnosis.
