microRNA-26a represses pancreatic cancer cell malignant behaviors by targeting E2F7

Wang, Liang; Li, Meijun; Chen, Fei

doi:10.1007/s12672-021-00448-z

Cited by 10 publications

(7 citation statements)

References 55 publications

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“…Pancreatic ductal carcinoma shows > 70% inactivation of the tumour suppressor p53 [47,48]. To verify the potential clinical relevance of p53-nuclear pore and p53-nuclear lamina axes in PDAC, we examined the expression of the members of these two families in a dataset of nearly 200 PDAC-patients.…”

Section: Resultsmentioning

confidence: 99%

p53 regulates expression of nuclear envelope components in cancer cells

et al. 2022

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Nuclear organisation and architecture are essential for the maintenance of genomic integrity as well as for the epigenetic regulations and gene expression. Disruption of lamin B1, major structural and functional member of the nuclear lamina, is observed in human laminopathies and in sporadic cancers, and leads to chromosomal rearrangements and alterations of gene expression. The tumour suppressor p53 has been shown to direct specific transcriptional programmes by regulating lamin A/C, however its relationship with lamin B1 has remained elusive. Here, we show that loss of p53 correlates with increased expression of members belonging to the nuclear pore complex and nuclear lamina and directly regulates transcription of lamin B1. We show that the genomic loci of a fraction of p53-dependent genes physically interact with lamin B1 and Nup210. This observation provides a possible mechanistic explanation for the p53-depedent changes of chromatin accessibility, with the consequent influence of expression and rearrangement of these genomic sites in pancreatic cancer. Overall, these data suggest a potential functional and biochemical regulatory network connecting p53 and nuclear architecture.

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Section: Resultsmentioning

confidence: 99%

p53 regulates expression of nuclear envelope components in cancer cells

et al. 2022

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“…Further studies are needed to establish the role of miR-7704 in cancer, especially in cervical cancer. The tumor suppressor activity of miR-26a-5p in cancer has been extensively described in many studies and has great potential in diagnostics ( 46 – 48 ). Rather, some studies have already addressed its therapeutic potential and identified its target mRNA in cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Selection of endogenous control and identification of significant microRNA deregulations in cervical cancer

et al. 2023

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IntroductionCervical cancer causes approximately 350,000 deaths each year. The availability of sensitive and specific diagnostic tests to detect cervical cancer in its early stages is essential to improve survival rates.MethodsIn this study, we compared two strategies for selecting endogenous controls: miRNA profiling by small-RNA sequencing and a commercially available microfluidic card with 30 recommended endogenous controls preloaded by the manufacturer. We used the RefFinder algorithm and coefficient of variation to select endogenous controls. We selected the combination of miR-181a-5p and miR-423-3p as the most optimal normalizer. In the second part of this study, we determined the differential expression (between tumor/non-tumor groups) of microRNA in cervical cancer FFPE tissue samples. We determined the comprehensive miRNA expression profile using small-RNA sequencing technology and verified the results by real-time PCR. We determined the relative expression of selected miRNAs using the 2-ΔΔCt method.ResultsWe detected statistically significant upregulation of miR-320a-3p, miR-7704, and downregulation of miR-26a-5p in the tumor group compared to the control group. The combination of these miRNAs may have the potential to be utilized as a diagnostic panel for cervical cancer. Using ROC curve analysis, the proposed panel showed 93.33% specificity and 96.97% sensitivity with AUC = 0.985.ConclusionsWe proposed a combination of miR-181a-5p and miR-423-3p as optimal endogenous control and detected potentially significant miRNAs (miR-320a-3p, miR-7704, miR-26a-5p). After further validation of our results, these miRNAs could be used in a diagnostic panel for cervical cancer.

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“…DKK1 could be served as an excellent target for cancer immunotherapy, and DKK1-CKAP4-PI3K/AKT signal pathway also plays a pivotal role in the proliferation of PC 46 . By targeting E2F7, miR-26a inhibited the malignant behaviors of PC cells 47 . In pancreatic adenosquamous carcinoma, EGFR-associated ligand-receptor pairs are activated in cell communications at a single-cell transcriptomics level 48 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive machine learning-generated classifier identifies pro-metastatic characteristics and predicts individual treatment in pancreatic cancer: A multicenter cohort study based on super-enhancer profiling

Chen¹,

Cao²,

Tang³

et al. 2023

Theranostics

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Rationale : Accumulating evidence illustrated that the reprogramming of the super-enhancers (SEs) landscape could promote the acquisition of metastatic features in pancreatic cancer (PC). Given the anatomy-based TNM staging is limited by the heterogeneous clinical outcomes in treatment, it is of great clinical significance to tailor individual stratification and to develop alternative therapeutic strategies for metastatic PC patients based on SEs. Methods : In our study, ChIP-Seq analysis for H3K27ac was performed in primary pancreatic tumors (PTs) and hepatic metastases (HMs). Bootstrapping and univariate Cox analysis were implemented to screen prognostic HM-acquired, SE-associated genes (HM-SE genes). Then, based on 1705 PC patients from 14 multicenter cohorts, 188 machine-learning (ML) algorithm integrations were utilized to develop a comprehensive super-enhancer-related metastatic (SEMet) classifier. Results : We established a novel SEMet classifier based on 38 prognostic HM-SE genes. Compared to other clinical traits and 33 published signatures, the SEMet classifier possessed robust and powerful performance in predicting prognosis. In addition, patients in the SEMet low subgroup owned dismal survival rates, more frequent genomic alterations, and more activated cancer immunity cycle as well as better benefits in immunotherapy. Remarkably, there existed a tight correlation between the SEMet low subgroup and metastatic phenotypes of PC. Among 18 SEMet genes, we demonstrated that E2F7 may promote PC metastasis through the upregulation of TGM2 and DKK1. Finally, after in silico screening of potential compounds targeted SEMet classifier, results revealed that flumethasone could enhance the sensitivity of metastatic PC to routine gemcitabine chemotherapy. Conclusion : Overall, our study provided new insights into personalized treatment approaches in the clinical management of metastatic PC patients.

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microRNA-26a represses pancreatic cancer cell malignant behaviors by targeting E2F7

Cited by 10 publications

References 55 publications

p53 regulates expression of nuclear envelope components in cancer cells

p53 regulates expression of nuclear envelope components in cancer cells

Selection of endogenous control and identification of significant microRNA deregulations in cervical cancer

Comprehensive machine learning-generated classifier identifies pro-metastatic characteristics and predicts individual treatment in pancreatic cancer: A multicenter cohort study based on super-enhancer profiling

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