Prognostic Impact of let-7e MicroRNA and Its Target Genes in Localized High-Risk Intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study

Fernández-Serra, Antonio; Moura, David S.; Sanchez-Izquierdo, M. Dolores; Calabuig, Silvia; López-Álvarez, María; Martínez-Martínez, Andrea; Carrasco-García, Irene María; Ramírez-Calvo, Marta; Blanco-Alcaina, Elena; López-Reig, Raquel; Obrador‐Hevia, Antònia; Alemany, Regina; Gutiérrez, Antonio; Hindi, Nadia; Poveda, Andrés; Löpez‐Guerrero, José Antonio; Martin‐Broto, Javier

doi:10.3390/cancers12102979

Cited by 9 publications

(3 citation statements)

References 50 publications

(51 reference statements)

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“…Remarkably, IGF1R has been found negatively regulated in let-7e overexpressing HCT-116 and LoVo cell lines [ 34 , 35 ]. Moreover, let-7e expression negatively correlates with ACVR1B in gastrointestinal stromal tumors (GIST) [ 36 ]. Altogether these results confirmed our observation in mice, and further sustain a possible involvement of let-7e in the differentiation process of intestinal epithelial cells rather than in the proliferation ones.…”

Section: Discussionmentioning

confidence: 99%

let-7e downregulation characterizes early phase colonic adenoma in APCMin/+ mice and human FAP subjects

et al. 2021

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The crypt-villus axis represents the essential unit of the small intestine, which integrity and functions are fundamental to assure tissue and whole-body homeostasis. Disruption of pathways regulating the fine balance between proliferation and differentiation results in diseases development. Nowadays, it is well established that microRNAs (miRNAs) play a crucial role in the homeostasis maintenance and perturbation of their levels may promote tumor development. Here, by using microarray technology, we analysed the miRNAs differentially expressed between the crypt and the villus in mice ileum. The emerged miRNAs were further validated by Real Time qPCR in mouse model (ApcMin/+), human cell lines and human tissue samples (FAP) of colorectal cancer (CRC). Our results indicated that miRNAs more expressed in the villi compartment are negatively regulated in tumor specimens, thus suggesting a close association between these microRNAs and the differentiation process. Particularly, from our analysis let-7e appeared to be a promising target for possible future therapies and a valuable marker for tumor staging, being upregulated in differentiated cells and downregulated in early-stage colonic adenoma samples.

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Section: Discussionmentioning

confidence: 99%

let-7e downregulation characterizes early phase colonic adenoma in APCMin/+ mice and human FAP subjects

et al. 2021

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“…40 Studies have revealed that IL10 mediates the activity of MAPK pathway, AMPK pathway, and JAK/STAT pathway, [41][42][43] and COL3A1 was identified as the regulatory factor of MAPK pathway. 44 MMP2, as a kind of downstream gene, was found to be regulated by MAPK pathway, Wnt pathway, and JAK/ STAT pathway, which were involved in the pathophysiological process of ischemia-reperfusion injury. [45][46][47] Thus, all the top 8 mRNAs may play important roles in the prediction and treatment of this disease, an area that warrants further research.…”

Section: Discussionmentioning

confidence: 99%

Potentially Functional microRNA-mRNA Regulatory Networks in Intestinal Ischemia-Reperfusion Injury: A Bioinformatics Analysis

Jiang¹,

Chen²,

Zhang³

et al. 2021

JIR

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Background: Intestinal ischemia-reperfusion (II/R) injury is a common clinical complication associated with high mortality, for which microRNA (miRNA) drives potentially its pathophysiological progression. MiRNAs regulate different messenger RNAs (mRNAs). However, the regulatory network between miRNAs and mRNAs in intestinal ischemiareperfusion injury is elusive. Methods: We analyzed the different expression of mRNAs and miRNAs in intestinal tissues from patients from three groups (arterial group (group A), venous group (group V), control group (group C)). Common differentially expressed (Co-DE) miRNAs and differentially expressed mRNAs were acquired via concerned analyses among the three groups. Co-DE mRNAs were shared parts of target mRNAs and differentially expression mRNAs. Cytoscape was employed to construct the regulatory network between miRNAs and mRNAs. Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway depicted the functions and potential pathway associated with Co-DE mRNAs. Using the STRING and Cytoscape, we found critical mRNAs in the protein-protein interaction (PPI) network. Results: The miRNA-mRNA network comprised 8 Co-DE miRNAs and 140 Co-DE mRNAs. Of note, 140 Co-DE mRNAs were targets of these 8 miRNAs, and their roles were established through the functional exploration via GO analysis and KEGG analysis. PPI network and Cytoscape revealed COL1A2, THY1, IL10, MMP2, SERPINH1, COL3A1, COL14A1, and P4HA1 as the top 8 key mRNAs. Conclusion:This study has demonstrated a miRNA-mRNA regulatory network in intestinal ischemia-reperfusion injury, and explored the key mRNAs and their potential functions. These findings could provide new insight into prognostic markers and therapeutic targets for patients with intestinal ischemia-reperfusion injury in clinical practice.

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“…In addition, genetic alterations, epigenetic mechanisms play a key role in disease biology by controlling gene expression at the post-transcriptional level [ 3 , 17 ]. In this context, research interest in miRNAs has quickly increased and several studies have investigated the role of miRNAs in GIST development, classification, and prognosis [ 18 , 19 , 20 ]. However, most of the studies focused on KIT mutants or KIT/PDGFRA wild-type (WT) GISTs, leaving the molecular biology of PDGFRA -mutant GISTs largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

miRNA Expression May Have Implications for Immunotherapy in PDGFRA Mutant GISTs

Ravegnini

Nannini

Indio

et al. 2022

IJMS

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Gastrointestinal stromal tumors (GISTs) harboring mutations in the PDGFRA gene occur in only about 5–7% of patients. The most common PDGFRA mutation is exon 18 D842V, which is correlated with specific clinico-pathological features compared to the other PDGFRA mutated GISTs. Herein, we present a miRNA expression profile comparison of PDGFRA D842V mutant GISTs and PDGFRA with mutations other than D842V (non-D842V). miRNA expression profiling was carried out on 10 patients using a TLDA miRNA array. Then, miRNA expression was followed by bioinformatic analysis aimed at evaluating differential expression, pathway enrichment, and miRNA-mRNA networks. We highlighted 24 differentially expressed miRNAs between D842V and non-D842V GIST patients. Pathway enrichment analysis showed that deregulated miRNAs targeted genes that are mainly involved in the immune response pathways. The miRNA-mRNA networks highlighted a signature of miRNAs/mRNA that could explain the indolent behavior of the D842V mutated GIST. The results highlighted a different miRNA fingerprint in PDGFRA D842V GISTs compared to non-D842Vmutated patients, which could explain the different biological behavior of this GIST subset.

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Prognostic Impact of let-7e MicroRNA and Its Target Genes in Localized High-Risk Intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study

Cited by 9 publications

References 50 publications

let-7e downregulation characterizes early phase colonic adenoma in APCMin/+ mice and human FAP subjects

let-7e downregulation characterizes early phase colonic adenoma in APCMin/+ mice and human FAP subjects

Potentially Functional microRNA-mRNA Regulatory Networks in Intestinal Ischemia-Reperfusion Injury: A Bioinformatics Analysis

miRNA Expression May Have Implications for Immunotherapy in PDGFRA Mutant GISTs

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