Integration of miRNA‐regulatory networks in hepatic stellate cells identifies TIMP3 as a key factor in chronic liver disease

Azar, Fida; Courtet, Kevin; Dekky, Bassil; Bonnier, Dominique; Dameron, Olivier; Colige, Alain; Legagneux, Vincent; Théret, Nathalie

doi:10.1111/liv.14476

Cited by 17 publications

(10 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, the upregulation of TIMP3 correlated with a downregulation of miR-221-3p and miR-222-3p in both CIS-resistant cell lines. Regulation of TIMP3 by miR-221-3p was described in diabetic retinopathy [ 68 ] and by miR-221-3p and miR-222-3p chronic liver disease [ 69 ]. Overexpression of miR-222-3p was associated with the downregulation of TIMP3 in osteosarcoma and promoted cells proliferation and invasion [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

The Profile of MicroRNA Expression and Potential Role in the Regulation of Drug-Resistant Genes in Cisplatin- and Paclitaxel-Resistant Ovarian Cancer Cell Lines

Kaźmierczak

Jopek

Sterzyńska

et al. 2022

IJMS

View full text Add to dashboard Cite

Ovarian cancer is the most lethal gynecological malignancy. The high mortality results from late diagnosis and the development of drug resistance. Drug resistance results from changes in the expression of different drug-resistance genes that may be regulated miRNA. The main aim of our study was to detect changes in miRNA expression levels in two cisplatin (CIS) and two paclitaxel (PAC)—resistant variants of the A2780 drug-sensitive ovarian cancer cell line—by miRNA microarray. The next goal was to identify miRNAs responsible for the regulation of drug-resistance genes. We observed changes in the expression of 46 miRNA that may be related to drug resistance. The overexpression of miR-125b-5p, miR-99a-5p, miR-296-3p, and miR-887-3p and downregulation of miR-218-5p, miR-221-3p, and miR-222-3p was observed in both CIS-resistant cell lines. In both PAC-resistant cell lines, we observed the upregulation of miR-221-3p, miR-222-3p, and miR-4485, and decreased expression of miR-551b-3p, miR-551b-5p, and miR-218-5p. Analysis of targets suggest that expression of important drug-resistant genes like protein Tyrosine Phosphatase Receptor Type K (PTPRK), receptor tyrosine kinase—EPHA7, Semaphorin 3A (SEMA3A), or the ATP-binding cassette subfamily B member 1 gene (ABCB1) can be regulated by miRNA.

show abstract

Section: Discussionmentioning

confidence: 99%

The Profile of MicroRNA Expression and Potential Role in the Regulation of Drug-Resistant Genes in Cisplatin- and Paclitaxel-Resistant Ovarian Cancer Cell Lines

Kaźmierczak

Jopek

Sterzyńska

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…miRNAs play a crucial role in maintaining adipocyte homeostasis, and they can also be used to identify novel molecular mechanisms underlying adipocyte function. miR-221 is one such miRNA, the expression of which declines during the course of adipocyte differentiation [24,61,62], which is up-regulated in the adipose tissue of obese human subjects [23], but is also associated with a number of cancers [46][47][48]. In this study, the effects of miR-221-3p on terminal adipocyte differentiation and the mechanisms involved were investigated.…”

Section: Discussionmentioning

confidence: 99%

Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p

Ahonen

Asghar

Parviainen

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractMicroRNA-221-3p (miR-221-3p) is associated with both metabolic diseases and cancers. However, its role in terminal adipocyte differentiation, adipocyte lipid metabolism, and lipid signaling in human disease are uncharacterized. miR-221-3p or its inhibitor were transfected into differentiating or mature human adipocytes. Triglyceride (TG) content and adipogenic gene expression were monitored, global lipidome analysis was carried out, and mechanisms underlying the effects of miR-221-3p were investigated. Finally, cross-talk between miR-221-3p expressing adipocytes and MCF-7 breast carcinoma (BC) cells was studied, and miR-221-3p expression in tumor-proximal adipose biopsies from BC patients analyzed. miR-221-3p overexpression inhibited terminal differentiation of adipocytes, as judged from reduced TG storage and gene expression of the adipogenic markers SCD1, GLUT4, FAS, DGAT1/2, AP2, ATGL and AdipoQ. The signaling adaptor protein 14-3-3γ was identified as a potential mediator of the miR-221-3p effects. Importantly, miR-221-3p overexpression inhibited de novo lipogenesis but increased the concentrations of ceramides and sphingomyelins, while reducing diacylglycerols, concomitant with suppression of sphingomyelin phosphodiesterase, ATP citrate lyase, and acid ceramidase. miR-221-3p expression was elevated in tumor proximal adipose tissue from patients with invasive BC. Conditioned medium of miR-221-3p overexpressing adipocytes stimulated the invasion and proliferation of BC cells, while medium of the BC cells enhanced miR-221-3p expression in adipocytes. miR-221-3p plays a pivotal role in the terminal differentiation of white adipocytes and their lipid composition. Elevated miR-221-3p impairs adipocyte lipid storage and differentiation, and modifies their ceramide, sphingomyelin, and diacylglycerol content. These alterations are relevant for metabolic diseases but may also affect cancer progression.

show abstract

“…The copyright holder for this preprint this version posted July 2, 2020. ; https://doi.org/10.1101/2020.06.30.180083 doi: bioRxiv preprint which is up-regulated in the adipose tissue of obese human subjects [23], but is also associated with a number of cancers [46][47][48]. In this study, the effects of miR-221-3p on terminal adipocyte differentiation and the mechanisms involved were investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Elevation of miR-221-3p has been associated with several cancers [46][47][48] and it is thus considered an oncomiR. Since an altered phenotype characterized by impaired lipid storage is a characteristic of tumor-associated adipocytes [49,50], we next studied the expression of miR-221-3p in the adipose tissue proximal to breast carcinoma (BC) in a total of 47 subjects undergoing mastectomy.…”

Section: Mimicking Tumor Microenvironment Enhances Mir-221-3p Expressionmentioning

confidence: 99%

Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p

Ahonen

Asghar

Parviainen

et al. 2021

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

) is associated with both metabolic diseases and cancers. However, its role in terminal adipocyte differentiation, adipocyte lipid metabolism, and lipid signaling in human disease are uncharacterized. miR-221-3p or its inhibitor were transfected into differentiating or mature human adipocytes. Triglyceride (TG) content and adipogenic gene expression were monitored, global lipidome analysis was carried out, and mechanisms underlying the effects of miR-221-3p were investigated. Finally, cross-talk between miR-221-3p expressing adipocytes and MCF-7 breast carcinoma (BC) cells was studied, and miR-221-3p expression in tumor-proximal adipose biopsies from BC patients analyzed. miR-221-3p overexpression inhibited terminal differentiation of adipocytes, as judged from reduced TG storage and gene expression of the adipogenic markers SCD1, GLUT4, FAS, DGAT1/2, AP2, ATGL and AdipoQ. The signaling adaptor protein 14-3-3γ was identified as a potential mediator of the miR-221-3p effects. Importantly, miR-221-3p overexpression inhibited de novo lipogenesis but increased the concentrations of ceramides and sphingomyelins, while reducing diacylglycerols, concomitant with suppression of sphingomyelin phosphodiesterase, ATP citrate lyase, and acid ceramidase. miR-221-3p expression was elevated in tumor proximal adipose tissue from patients with invasive BC. Conditioned medium of miR-221-3p overexpressing adipocytes stimulated the invasion and proliferation of BC cells, while medium of the BC cells enhanced miR-221-3p expression in adipocytes. miR-221-3p plays a pivotal role in the terminal differentiation of white adipocytes and their lipid composition. Elevated miR-221-3p impairs adipocyte lipid storage and differentiation, and modifies their ceramide, sphingomyelin, and diacylglycerol content. These alterations are relevant for metabolic diseases but may also affect cancer progression.

show abstract

Integration of miRNA‐regulatory networks in hepatic stellate cells identifies TIMP3 as a key factor in chronic liver disease

Cited by 17 publications

References 48 publications

The Profile of MicroRNA Expression and Potential Role in the Regulation of Drug-Resistant Genes in Cisplatin- and Paclitaxel-Resistant Ovarian Cancer Cell Lines

The Profile of MicroRNA Expression and Potential Role in the Regulation of Drug-Resistant Genes in Cisplatin- and Paclitaxel-Resistant Ovarian Cancer Cell Lines

Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p

Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p

Contact Info

Product

Resources

About