Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis

Sousa, Marta Correia de; Calo, Nicolas; Sobolewski, Cyril; Gjorgjieva, Monika; Clément, Sophie; Maeder, Christine; Dolicka, Dobrochna; Fournier, Margot; Vinet, Laurent; Montet, Xavier; Dufour, Jean–François; Humar, Bostjan; Negro, Francesco; Sempoux, Christine; Foti, Michelangelo

doi:10.3390/cancers13194983

Cited by 22 publications

(11 citation statements)

References 131 publications

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“…In agreement, our data indicate that TIA1 loss is associated with an increase in several secreted factors (e.g., S100 family members, osteopontin), which could potentially foster HCC development by promoting inflammation, hepatic fibrosis, and immune escape of cancer cells, as previously demonstrated [ 4 ]. Further illustrating discrepant data arising from in vivo versus in vitro experimental settings, we previously reported that another AUBP tristetraprolin (TTP), or miRNAs such as miR-21, also display opposite functions in vitro versus in vivo in cancer-related processes [ 10 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…HCC development is tightly associated with the deregulated activity of various AUBPs, e.g., HuR [ 8 ] or T-cell-restricted intracellular antigen-1 (TIA1) [ 9 ]. Moreover, our previous work has uncovered other AUBPs deregulated in human HCC [ 10 ]. This study identifies TIA1 as a potential TS, whose function in HCC remains poorly known.…”

Section: Introductionmentioning

confidence: 99%

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TIA1 Loss Exacerbates Fatty Liver Disease but Exerts a Dual Role in Hepatocarcinogenesis

Dolicka

Zahorán

Sousa

et al. 2022

Cancers

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Alterations in specific RNA-binding protein expression/activity importantly contribute to the development of fatty liver disease (FLD) and hepatocellular carcinoma (HCC). In particular, adenylate–uridylate-rich element binding proteins (AUBPs) were reported to control the post-transcriptional regulation of genes involved in both metabolic and cancerous processes. Herein, we investigated the pathophysiological functions of the AUBP, T-cell-restricted intracellular antigen-1 (TIA1) in the development of FLD and HCC. Analysis of TIA1 expression in mouse and human models of FLD and HCC indicated that TIA1 is downregulated in human HCC. In vivo silencing of TIA1 using AAV8-delivered shRNAs in mice worsens hepatic steatosis and fibrosis induced by a methionine and choline-deficient diet and increases the hepatic tumor burden in liver-specific PTEN knockout (LPTENKO) mice. In contrast, our in vitro data indicated that TIA1 expression promoted proliferation and migration in HCC cell lines, thus suggesting a dual and context-dependent role for TIA1 in tumor initiation versus progression. Consistent with a dual function of TIA1 in tumorigenesis, translatome analysis revealed that TIA1 appears to control the expression of both pro- and anti-tumorigenic factors in hepatic cancer cells. This duality of TIA1′s function in hepatocarcinogenesis calls for cautiousness when considering TIA1 as a therapeutic target or biomarker in HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TIA1 Loss Exacerbates Fatty Liver Disease but Exerts a Dual Role in Hepatocarcinogenesis

Dolicka

Zahorán

Sousa

et al. 2022

Cancers

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“…Moreover, miR-21 downregulation is associated with the progression of the disease from NASH to HCC, as was demonstrated in animal and human HCC models [ 82 ]. The aforementioned phenomenon is attributed to the disruption of several signaling pathways, such as STAT3, AKT/PKB, and TGF-b [ 83 ].…”

Section: The Emerging Role Of Mirnas In Hccmentioning

confidence: 98%

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches

Koustas

Trifylli²,

Sarantis

et al. 2023

IJMS

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Hepatocellular carcinoma (HCC) constitutes a frequent highly malignant form of primary liver cancer and is the third cause of death attributable to malignancy. Despite the improvement in the therapeutic strategies with the exploration of novel pharmacological agents, the survival rate for HCC is still low. Shedding light on the multiplex genetic and epigenetic background of HCC, such as on the emerging role of microRNAs, is considered quite promising for the diagnosis and the prediction of this malignancy, as well as for combatting drug resistance. MicroRNAs (miRNAs) constitute small noncoding RNA sequences, which play a key role in the regulation of several signaling and metabolic pathways, as well as of pivotal cellular functions such as autophagy, apoptosis, and cell proliferation. It is also demonstrated that miRNAs are significantly implicated in carcinogenesis, either acting as tumor suppressors or oncomiRs, while aberrations in their expression levels are closely associated with tumor growth and progression, as well as with local invasion and metastatic dissemination. The arising role of miRNAs in HCC is in the spotlight of the current scientific research, aiming at the development of novel therapeutic perspectives. In this review, we will shed light on the emerging role of miRNAs in HCC.

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“…Targeting delivery of therapeutic miR-21 has been reported to improve the recovery of cardiac function after myocardial infarction [ 53 ]. However, miR-21 is also overexpressed in a variety of diseases, including cancer, so it is also regarded as an oncomiR [ 54 ]. miR-34, as an aging-related miRNA, is related to cardiac dysfunction and related cardiovascular diseases.…”

Section: Mirnas: Regulatory Factors Of the Heartmentioning

confidence: 99%

MicroRNA in the Diagnosis and Treatment of Doxorubicin-Induced Cardiotoxicity

Kuang

Tan

et al. 2023

Biomolecules

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Doxorubicin (DOX), a broad-spectrum chemotherapy drug, is widely applied to the treatment of cancer; however, DOX-induced cardiotoxicity (DIC) limits its clinical therapeutic utility. However, it is difficult to monitor and detect DIC at an early stage using conventional detection methods. Thus, sensitive, accurate, and specific methods of diagnosis and treatment are important in clinical practice. MicroRNAs (miRNAs) belong to non-coding RNAs (ncRNAs) and are stable and easy to detect. Moreover, miRNAs are expected to become biomarkers and therapeutic targets for DIC; thus, there are currently many studies focusing on the role of miRNAs in DIC. In this review, we list the prominent studies on the diagnosis and treatment of miRNAs in DIC, explore the feasibility and difficulties of using miRNAs as diagnostic biomarkers and therapeutic targets, and provide recommendations for future research.

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Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis

Cited by 22 publications

References 131 publications

TIA1 Loss Exacerbates Fatty Liver Disease but Exerts a Dual Role in Hepatocarcinogenesis

TIA1 Loss Exacerbates Fatty Liver Disease but Exerts a Dual Role in Hepatocarcinogenesis

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches

MicroRNA in the Diagnosis and Treatment of Doxorubicin-Induced Cardiotoxicity

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