<scp>MicroRNA</scp>‐216a targets <scp>WT1</scp> expression and regulates <scp>KRT7</scp> transcription to mediate the progression of pancreatic cancer—A transcriptome analysis

Wang, Wei; Wang, Jie; Yang, Chuanxin; Wang, Jian

doi:10.1002/iub.2468

Cited by 12 publications

(12 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KRT7 transcription is activated by WT1 expression, which promote the migration and invasion of PC. Furthermore, silencing KRT7 was found to diminish this progression (9). However, the roles of SDCBP in PC remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Overall, three proteins were validated, namely, CLIC1, KRT7, and syntenin (SDCBP). CLIC1 and KRT7 are involved in PC migration and invasion (8,9); however, the role of SDCBP in PC remains unclear. Syntenin is a multifunctional scaffold protein, which contains two PDZ domains and promotes cellular migration and invasion through epithelial-mesenchymal transition (EMT) (10)(11)(12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Syntenin Regulated by miR-216b Promotes Cancer Progression in Pancreatic Cancer

Chen

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Outcomes for patients with pancreatic cancer (PC) are poor; therefore, there is an urgent need to identify novel therapeutic targets involved in the progression of PC. We previously identified 161 differentially expressed proteins (DEPs) in PC. Syntenin (SDCBP) was identified as a survival-related protein through integrated, survival, and Cox analyses. High expression of SDCBP was associated with a poor prognosis in PC tissue and promoted the proliferation, migration, and invasion of PC cells, and induced epithelial–mesenchymal transition (EMT) via the PI3K/AKT pathway. Additionally, we elucidated the regulatory mechanism underlying these roles of SDCBP at the post-transcriptional level. microRNAs (miRNAs) of SDCBP were predicted using bioinformatics. Low levels of miR-216b expression were confirmed in PC tissues and were negatively correlated with SDCBP expression. miR-216b was found to directly regulate SDCBP expression through luciferase reporter assays. Furthermore, agomiR-216b restrained PC proliferation, migration, invasion, and EMT via the PI3K/AKT pathway, whereas antagomiR-216b facilitated this process. Notably, the knockout of SDCBP counteracted the effect of antagomiR-216b in PC, which suggested that miR-216b and SDCBP represent molecular targets underlying PC progression and EMT. Finally, the results were validated in in vivo studies. These findings indicated that low expression of miR-216b and the oncogene SDCBP contributes to PC migration, invasion, and EMT, and that they have potential as future therapeutic targets for patients with PC.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Syntenin Regulated by miR-216b Promotes Cancer Progression in Pancreatic Cancer

Chen

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…KRT7 belongs to type II cytokeratin involving in cytoskeleton remodeling, epithelial intermediate filaments formation, and motility enhancement of cells [35]. Previous studies have indicated that KRT7 is overexpressed in many cancers, including ovarian, gastric, colorectal, and pancreatic cancer, which can facilitate the migration and invasion of cancer cells [36][37][38][39]. AURKA is a regulator kinase of cell cycle involved in microtubule formation, spindle pole stabilization during chromosome segregation, and functionally contributes to tumorigenesis and progression [40].…”

Section: Discussionmentioning

confidence: 99%

Construction of a novel model based on cell-in-cell-related genes and validation of KRT7 as a biomarker for predicting survival and immune microenvironment in pancreatic cancer

et al. 2022

View full text Add to dashboard Cite

Background Pancreatic cancer (PC) is a highly malignant tumor featured with high intra-tumoral heterogeneity and poor prognosis. Cell-in-cell (CIC) structures have been reported in multiple cancers, and their presence is associated with disease progression. Nonetheless, the prognostic values and biological functions of CIC-related genes in PC remain poorly understood. Methods The sequencing data, as well as corresponding clinicopathological information of PC were collected from public databases. Random forest screening, least absolute shrinkage, and selection operator (LASSO) regression and multivariate Cox regression analysis were performed to construct a prognostic model. The effectiveness and robustness of the model were evaluated using receiver operating characteristic (ROC) curves, survival analysis and establishing the nomogram model. Functional enrichment analyses were conducted to annotate the biological functions. The immune infiltration levels were evaluated by ESTIMATE and CIBERSORT algorithms. The expression of KRT7 (Keratin 7) was validated by quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry (IHC) staining. The CIC formation, cell clusters, cell proliferation, migration and invasion assays were applied to investigate the effects of silencing the expression of KRT7. Results A prognostic model based on four CIC-related genes was constructed to stratify the patients into the low- and high-risk subgroups. The high-risk group had a poorer prognosis, higher tumor mutation burden and lower immune cell infiltration than the low-risk group. Functional enrichment analyses showed that numerous terms and pathways associated with invasion and metastasis were enriched in the high-risk group. KRT7, as the most paramount risk gene in the prognostic model, was significantly associated with a worse prognosis of PC in TCGA dataset and our own cohort. High expression of KRT7 might be responsible for the immunosuppression in the PC microenvironment. KRT7 knockdown was significantly suppressed the abilities of CIC formation, cell cluster, cell proliferation, migration, and invasion in PC cell lines. Conclusions Our prognostic model based on four CIC-related genes has a significant potential in predicting the prognosis and immune microenvironment of PC, which indicates that targeting CIC processes could be a therapeutic option with great interests. Further studies are needed to reveal the underlying molecular mechanisms and biological implications of CIC phenomenon and related genes in PC progression.

show abstract

“…The major roles of keratin include maintaining cellular integrity and regulating cell growth, migration, and apoptosis in normal tissues and cancer tissues ( 23 ). Several studies have identified Krt7 as an immunohistochemical biomarker, and the overexpression of Krt7 is considered a poor prognostic factor in the variety of cancers, such as renal tumors, lung cancer, and intrahepatic cholangiocarcinoma ( 24 , 25 ). Cadherins are a large superfamily comprising 350 members.…”

Section: Discussionmentioning

confidence: 99%

Analysis and identification of potential key genes in hepatic ischemia-reperfusion injury

Li¹,

Su²,

Li³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background: Hepatic ischemia-reperfusion injury (HIRI) is an unavoidable surgical complication after liver transplantation, but current HIRI treatments cannot achieve satisfactory clinical outcomes. Thus, safer and more effective prevention and treatment methods need to be explored.Methods: Transcriptome messenger ribonucleic acid (mRNA) and long non-coding RNA (lncRNA) sequencing data were obtained from male Sprague-Dawley rats, and these data were used to identify the differentially expressed genes (DEGs) and differentially expressed lncRNAs (DE-lncRNAs) between the HIRI and control samples. A protein-protein interaction (PPI) network was also constructed for the DE-mRNAs to identify candidate genes, and the receiver operating characteristic curves of the 21 candidate genes were plotted to evaluate the diagnostic value of the candidate genes for HIRI. A random forest (RF) model, support vector machine model and generalized linear model were constructed based on the candidate genes. A gene set enrichment analysis (GSEA) of the key genes was conducted to determine the enriched pathways in the high expression groups. The miRWalk and miRanda database were used to constructed the lncRNA-miRNA-mRNA network. Finally, the expressions of the key genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR).Results: A total of 256 DEGs and 67 DE-lncRNAs were identified in the HIRI and control samples. To explore the interactions between the DE-mRNAs, a PPI network of 130 DEGs was constructed. Further, 21 genes were selected as the candidate genes. Subsequently, 6 genes [i.e., Keratin-14 (Krt14), Uroplakin 3B (Upk3b), Keratin 7 (Krt7), Cadherin 3 (Cdh3), mesothelin (Msln), and Glypican 3 (Gpc3)] in the RF model were defined as the key genes. The GSEA results indicated that these key genes were enriched in the terms of extracellular structure organization, and extracellular matrix organization. Moreover, a lncRNA-miRNA-mRNA network was constructed with 4 lncRNAs, 5 mRNAs, and 11 miRNAs. Finally, the results indicated that the expression of Krt14, Upk3b, Msln, and Gpc3 were more highly expressed in the control samples than the HIRI samples.Conclusions: A total of 6 key genes (i.e., Krt14, Upk3b, Krt7, Cdh3, Msln, and Gpc3) were identified. Our findings provide novel ideas for the diagnosis and treatment of HIRI.

show abstract

MicroRNA‐216a targets WT1 expression and regulates KRT7 transcription to mediate the progression of pancreatic cancer—A transcriptome analysis

Cited by 12 publications

References 32 publications

Syntenin Regulated by miR-216b Promotes Cancer Progression in Pancreatic Cancer

Syntenin Regulated by miR-216b Promotes Cancer Progression in Pancreatic Cancer

Construction of a novel model based on cell-in-cell-related genes and validation of KRT7 as a biomarker for predicting survival and immune microenvironment in pancreatic cancer

Analysis and identification of potential key genes in hepatic ischemia-reperfusion injury

Contact Info

Product

Resources

About