Microenvironment‐induced TIMP2 loss by cancer‐secreted exosomal miR‐4443 promotes liver metastasis of breast cancer

Wang, Jinyan; Zhang, Qian; Wang, Dandan; Yang, Su-Jin; Zhou, Siying; Xu, Hanzi; Zhang, Heda; Zhong, Shanliang; Feng, Jifeng

doi:10.1002/jcp.29507

Cited by 51 publications

(40 citation statements)

References 56 publications

(63 reference statements)

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“…miRNAs are a group of endogenous, highly conserved, noncoding RNAs (18-25 nts in length) that regulate gene expression both transcriptionally and posttranscriptionally [87][88][89][90]. Accumulating evidence has demonstrated remarkable relationship between the expression patterns of miRNAs and IGF2BP2 and development as well as progression of tumors.…”

Section: Igf2bp2 With Mirnas In Cancersmentioning

confidence: 99%

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

2021

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The human insulin-like growth factor 2 (IGF2) mRNA binding proteins 2 (IGF2BP2/IMP2) is an RNA-binding protein that regulates multiple biological processes. Previously, IGF2BP2 was thought to be a type 2 diabetes (T2D)-associated gene. Indeed IGF2BP2 modulates cellular metabolism in human metabolic diseases such as diabetes, obesity and fatty liver through post-transcriptional regulation of numerous genes in multiple cell types. Emerging evidence shows that IGF2BP2 is an N6-methyladenosine (m6A) reader that participates in the development and progression of cancers by communicating with different RNAs such as microRNAs (miRNAs), messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Additionally, IGF2BP2 is an independent prognostic factor for multiple cancer types. In this review, we summarize the current knowledge on IGF2BP2 with regard to diverse human metabolic diseases and its potential for cancer prognosis.

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Section: Igf2bp2 With Mirnas In Cancersmentioning

confidence: 99%

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

2021

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“…The high expression of circulating miR-4454 has been documented in two studies conducted in bladder cancer and melanoma [ 21 , 22 ]. Contrasting evidence regarding miR-4443 were reported in several cancer settings, such as breast and ovarian cancer [ 23 , 24 , 25 ]. Only one study has associated the high expression of miR-4530 with chemosensitivity in breast cancer [ 26 ].…”

Section: Discussionmentioning

confidence: 93%

Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma

Pratama

Visintin

Crocè

et al. 2020

Cancers

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The clinical outcome of hepatocellular carcinoma (HCC) treatment remains unsatisfactory, contributing to the high mortality of HCC worldwide. Circulating miRNAs have the potential to be a predictor of therapy response. Microarray profiling was performed in serum samples of 20 HCC patients before treatment. Circulating miRNAs associated with treatment response were validated in 86 serum HCC samples using the qRT-PCR system. Patients were treated either with curative treatments (resection or radiofrequency) or trans-arterial chemoembolization (TACE), and grouped according to therapy response in complete responders (CR) and partial responders or progressive disease (PRPD), following mRECIST criteria. Four miRNA candidates from the discovery phase (miR-4443, miR-4454, miR-4492, and miR-4530) were validated. Before therapy, miR-4454 and miR-4530 were up-regulated in CR to curative treatments (2.83 fold, p = 0.02 and 2.33 fold, p = 0.008, respectively) and were able to differentiate CR from PRPD (area under the curve (AUC) = 0.74, sens/spec 79/63% and AUC = 0.77, sens/spec 72/73%). On the contrary, miR-4443 was 1.95 times down-regulated in CR (p = 0.05) with an AUC of 0.72 (sens = 70%, spec = 60%) in distinguishing CR vs. PRPD). The combination of the three miRNAs was able to predict the response to curative treatment with an AUC of 0.84 (sens = 72%, spec = 75%). The higher levels of miR-4454 and miR-4530 in were associated to longer overall survival (HR = 2.79, p = 0.029 and HR = 2.97, p = 0.011, respectively). Before TACE, miR-4492 was significantly up-regulated in CR patients (FC = 2.67, p = 0.01) and able to differentiate CR from PRPD (AUC = 0.84, sens/spec 84.6/71%). We demonstrated that different miRNAs predictors can be used as potential prognostic circulating biomarkers according to the selected treatment for HCC.

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“…It gradually moves away from chemotherapy, which has been the standard treatment of CC for decades, toward immunotherapy that modulates immune responses against tumor cells [27,28] . In the last few years, TME was found to play a vital role in the initiation and progression of tumorigenesis [29][30][31][32] . Researches indicated that TIME was closely related with the prognosis of cancers, including hepatocellular carcinoma [33] , lung adenocarcinoma, lung squamous cell carcinoma [34] and so on.…”

Section: Discussionmentioning

confidence: 99%

TGFβ1: an Indicator for Tumor Immune Microenvironment (TIME) of Colon Cancer from a Comprehensive Analysis of TCGA

Wang

Wang²,

et al. 2020

Preprint

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Background: Tumor microenvironment (TME) and tumor-infiltrating immune cells (TIC) greatly participated in the genesis and development of colon cancer (CC). However, there are few researches exploring the dynamic modulation of TME. Methods: In our study, we analyzed the proportion of immune/stromal component and TIC in TME of 473 CC samples and 41 normal samples from The Cancer Genome Atlas (TCGA) database through ESTIMATE and CIBERSORT algorithm. Correlation analysis was carried out to evaluate the association between immune/stromal component in TME and clinicopathological characteristics of CC patients. The difference analysis was performed to obtain the differentially expressed genes (DEGs). These DEGs were further analyzed by gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, protein–protein interaction (PPI) network construction and COX regression analysis. Transforming growth factor β1 (TGFβ1) was finally overlapping from the above analysis. Furthermore, TGFβ1 was analyzed by paired analysis, Gene Set Enrichment Analysis (GSEA). The intersection between the difference analysis and correlation analysis was also conducted to learn the association between TGFβ1 and TICs.Results: Our result showed that immune component in TME was negatively related with the stages of CC. GO and KEGG enrichment analysis revealed that 1110 DEGs obtained from difference analysis were mainly enriched in immune-related activities. The intersection analysis between PPI network and COX regression analysis indicted that TGFβ1 was significantly associated with the communication of genes in PPI network and the Hazard Ratio (HR) of CC patients’ survival. In addition, TGFβ1 was up-regulated in the tumor samples and significantly related with poor prognosis of CC patients. Further GSEA suggested that genes in TGFβ1 up-regulated group were primarily enriched in immune-related activities and the function of TGFβ1 might depend on the communications with TICs, including T cells CD4 naïve and T cells regulatory (Tregs). Conclusions: The expression of TGFβ1 might be an indicator for tumor immune microenvironment (TIME) of CC and sever as a prognostic factor of CC. Drugs targeting TGFβ1 might be a potential immunotherapy for CC patients in the future.

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Microenvironment‐induced TIMP2 loss by cancer‐secreted exosomal miR‐4443 promotes liver metastasis of breast cancer

Cited by 51 publications

References 56 publications

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma

TGFβ1: an Indicator for Tumor Immune Microenvironment (TIME) of Colon Cancer from a Comprehensive Analysis of TCGA

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