MicroRNA-124 inhibits hepatic stellate cells inflammatory cytokines secretion by targeting IQGAP1 through NF-κB pathway

Yang, Jun; Xu, Changqing; Wu, Maomao; Wu, Ying; Jia, Xiao-Di; Zhou, Chang; Zhang, Xian‐Zheng; Ge, Shuping; Zeng, Li; Zhang, Lingling

doi:10.1016/j.intimp.2021.107520

Cited by 17 publications

(9 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent study, IQGAP1, which is increased in CCl 4induced mouse liver fibrosis, is reported to mediate inflammatory factor expression via affecting nuclear factor kB (NF-kB) signaling in TNF-a-treated LX-2 cells. 11 Our results also illustrate that IQGAP1 is increased in MCDHF-diet-or BDL-induced liver fibrogenesis and is positively correlated with fibrosis hallmarks. In addition, silencing IQGAP1 prominently prevents hepatic fibrosis induced by MCDHF diet.…”

Section: Discussionsupporting

confidence: 60%

See 1 more Smart Citation

Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver

Chang

Liu

et al. 2022

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

IQ motif-containing guanosine triphosphatase (GTPase)-activating protein 1 (IQGAP1) is a cytosolic scaffolding protein involved in cell migration. Our previous studies suggest sphingosine 1-phosphate (S1P) triggers bone marrow (BM) mesenchymal stromal cells (BMSCs) to damaged liver, thereby promoting liver fibrosis. However, the role of IQGAP1 in S1Pinduced BMSC migration and liver fibrogenesis remains unclear. Chimeric mice of BM cell labeled by EGFP were used to build methionine-choline-deficient and high-fat (MCDHF)-dietinduced mouse liver fibrosis. IQGAP1 small interfering RNA (siRNA) was utilized to silence IQGAP1 in vivo. IQGAP1 expression is significantly elevated in MCDHF-diet-induced mouse fibrotic livers. Positive correlations are presented between IQ-GAP1 and fibrosis hallmarks expressions in human and mouse fibrotic livers. In vitro, depressing IQGAP1 expression blocks S1P-induced motility and cytoskeleton remodeling of BMSCs. S1P facilitates IQGAP1 aggregating to plasma membrane via S1P receptor 3 (S1PR 3 ) and Cdc42/Rac1. In addition, IQGAP1 binds to Cdc42/Rac1, regulating S1P-induced activation of Cdc42/Rac1 and mediating BMSC migration in concert. In vivo, silencing IQGAP1 reduces the recruitment of BMSCs to impaired liver and effectively alleviates liver fibrosis induced by MCDHF diet. Together, silencing IQGAP1 relieves liver fibrosis by blocking BMSC migration, providing an effective therapeutic strategy for liver fibrosis.

show abstract

Section: Discussionsupporting

confidence: 60%

“…9,10 In liver fibrogenesis, a recent study reports that IQGAP1 is increased in CCl 4 -induced mouse liver fibrosis and mediates inflammatory factor expression in tumor necrosis factor alpha (TNF-a)-treated LX-2 cells. 11 However, research concerning the regulatory role of IQGAP1 in hepatic fibrosis is still in great request.…”

Section: Introductionmentioning

confidence: 99%

Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver

Chang

Liu

et al. 2022

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

show abstract

“…Furthermore, the overexpression of IQGAP1 in activated LX-2 cells promoted the secretion of inflammatory cytokines. These findings suggest the putative role of IQGAP1 in liver inflammation and fibrogenesis ( 85 ). The increased levels of IQGAP1 in fibrotic liver were also confirmed by Ma and colleagues, who further demonstrated the cell type fraction responsible for such increase ( 79 ).…”

Section: The Relationship Between Iqgaps and Liver Diseasesmentioning

confidence: 77%

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

et al. 2022

View full text Add to dashboard Cite

IQ motif-containing GTPase-activating proteins (IQGAPs) are a class of scaffolding proteins, including IQGAP1, IQGAP2, and IQGAP3, which govern multiple cellular activities by facilitating cytoskeletal remodeling and cellular signal transduction. The role of IQGAPs in cancer initiation and progression has received increasing attention in recent years, especially in hepatocellular carcinoma (HCC), where the aberrant expression of IQGAPs is closely related to patient prognosis. IQGAP1 and 3 are upregulated and are considered oncogenes in HCC, while IQGAP2 is downregulated and functions as a tumor suppressor. This review details the three IQGAP isoforms and their respective structures. The expression and role of each protein in different liver diseases and mainly in HCC, as well as the underlying mechanisms, are also presented. This review also provides a reference for further studies on IQGAPs in HCC.

show abstract

“…Moreover, miR-124 is known to limit renal fibrosis [135]. Based on this evidence, Yang et al [129] explored the contribution of miR-124 in LF. In a CCl4-induced liver fibrosis mice model, the authors showed that miR-124 was downregulated, particularly in HSCs [9], the liver cell type mostly involved in LF.…”

Section: Ncrnas In Liver Fibrosis and Hccmentioning

confidence: 99%

Targeting Non-Coding RNAs for the Development of Novel Hepatocellular Carcinoma Therapeutic Approaches

et al. 2023

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) remains a global health challenge, representing the third leading cause of cancer deaths worldwide. Although therapeutic advances have been made in the few last years, the prognosis remains poor. Thus, there is a dire need to develop novel therapeutic strategies. In this regard, two approaches can be considered: (1) the identification of tumor-targeted delivery systems and (2) the targeting of molecule(s) whose aberrant expression is confined to tumor cells. In this work, we focused on the second approach. Among the different kinds of possible target molecules, we discuss the potential therapeutic value of targeting non-coding RNAs (ncRNAs), which include micro interfering RNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). These molecules represent the most significant RNA transcripts in cells and can regulate many HCC features, including proliferation, apoptosis, invasion and metastasis. In the first part of the review, the main characteristics of HCC and ncRNAs are described. The involvement of ncRNAs in HCC is then presented over five sections: (a) miRNAs, (b) lncRNAs, (c) circRNAs, (d) ncRNAs and drug resistance and (e) ncRNAs and liver fibrosis. Overall, this work provides the reader with the most recent state-of-the-art approaches in this field, highlighting key trends and opportunities for more advanced and efficacious HCC treatments.

show abstract

MicroRNA-124 inhibits hepatic stellate cells inflammatory cytokines secretion by targeting IQGAP1 through NF-κB pathway

Cited by 17 publications

References 64 publications

Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver

Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

Targeting Non-Coding RNAs for the Development of Novel Hepatocellular Carcinoma Therapeutic Approaches

Contact Info

Product

Resources

About