TIMP-3 Expression Associates with Malignant Behaviors and Predicts Favorable Survival in HCC

Gu, Xuefeng; Fu, Maoying; Ding, Yuqin; Ni, Huihui; Zhang, Wei; Zhu, Yanfang; Tang, Xiaojun; Xiong, Lin; Jiang, Li; Qiu, Liang; Xu, Jiaren; Zhu, Jin

doi:10.1371/journal.pone.0106161

Cited by 35 publications

(29 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have identified TIMP3 as a tumor suppressor as its expression is silenced in malignant tumors including hepatocellular carcinoma (HCC) 18 , 19 . To evaluate the role of hepatic Timp3 overexpression in HCC, we have used a model of diethylnitrosamine (DEN) administration combined with dietary induced obesity.…”

Section: Resultsmentioning

confidence: 99%

Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease and hepatocellular carcinoma

Casagrande

Mauriello

Bischetti

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions, ranging from non-progressive bland steatosis to hepatocarcinoma. Tissue inhibitor of metalloproteinase 3 (Timp3) has a role in the pathogenesis of fatty liver disease associated with obesity and is silenced during metabolic disorders and liver cancer. We generated an hepatocyte-specific TIMP3 ‘gain-of-function’ mouse model under the control of the Albumin promoter (AlbT3) and investigated its effects during high-fat diet (HFD). After 16 weeks of HFD, TIMP3 overexpression significantly improved glucose metabolism, hepatic fatty acid oxidation and cholesterol homeostasis. In AlbT3 mice CYP7A1, MDR3 and MRP2 gene expressions were observed, consistent with higher bile acid synthesis and export. Next, to evaluate the role of A Disintegrin and Metalloproteinase 17 (ADAM17), a crucial target of TIMP3, in these processes, we created mice deficient in Adam17 specifically in hepatocyte (A17LKO) or in myeloid lineage (A17MKO), founding that only A17LKO showed improvement in liver steatosis induced by HFD. Moreover, both, AlbT3 and A17LKO significantly reduced diethylnitrosamine-initiated, HFD-promoted hepatic tumorigenesis assessed by tumor multiplicity and total tumor area. Taken together, these data indicate that hepatic TIMP3 can slow progression of NAFLD, and tumorigenesis, at least in part, through the regulation of ADAM17 activity.

show abstract

Section: Resultsmentioning

confidence: 99%

Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease and hepatocellular carcinoma

Casagrande

Mauriello

Bischetti

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Yu J et al linked the circRNA cSMARCA5/miR-17-3p/miR-181b-5p/TIMP3 regulatory pathway to EMT in HCC [125]. TIMP3 has been reported to be a tumor cell suppressor in several studies and inactivates the EMT program [126,127]. It has been found that the decrease in circRNA cSMARCA5 facilitates HCC cell migration and metastasis and downregulates TIMP3 transcription by absorbing miR-17-3p and miR-181b-5p [125].…”

Section: Other Pathways Related To Circrnasmentioning

confidence: 99%

Functional roles of circular RNAs during epithelial-to-mesenchymal transition

Shang¹,

Li²,

Quan³

et al. 2019

Mol Cancer

View full text Add to dashboard Cite

Cancer has become a major health issue worldwide, contributing to a high mortality rate. Tumor metastasis is attributed to the death of most patients. Epithelial-to-mesenchymal transition (EMT) plays a vital role in inducing metastasis. During EMT, epithelial cells lose their characteristics, such as cell-to-cell adhesion and cell polarity, and cells gain motility, migratory potential, and invasive properties to become mesenchymal stem cells. Circular RNAs (circRNAs) are closely associated with tumor metastasis and patient prognosis, as revealed by increasing lines of evidence. CircRNA is a type of single-stranded RNA that forms a covalently closed continuous loop. CircRNAs are insensitive to ribonucleases and are widespread in body fluids. This work is the first review on EMT-related circRNAs. In this review, we briefly discuss the characteristics and functions of circRNAs. The correlation of circRNAs with EMT has been reported, and we discuss the ways circRNAs can regulate EMT progression through EMT transcription factors, EMT-related signaling pathways, and other mechanisms. This work summarizes current studies on EMTrelated circRNAs in various cancers and provides a theoretical basis for the use of EMT-related circRNAs in targeted management and therapy.

show abstract

“…Immunohistochemical (IHC) analysis was performed as described previously. [ 47,48 ] In brief, formalin-fi xed, paraffi n-embedded tissues from the mice were prepared and paraffi n sections were incubated with a primary TIMP3 Rabbit mAb (Cell Signaling Technology, USA) in PBS, washed and then incubated with a horseradish peroxidase-conjugated antibody (Santa Cruz Biotechnology, CA, USA). Negative controls were included by replacement of the primary antibody with PBS.…”

Section: −1mentioning

confidence: 99%

Folic‐Acid‐Mediated Functionalized Gold Nanocages for Targeted Delivery of Anti‐miR‐181b in Combination of Gene Therapy and Photothermal Therapy against Hepatocellular Carcinoma

Huang

Duan

Wang

et al. 2016

Adv Funct Materials

120

View full text Add to dashboard Cite

Therapeutic strategies based on modulation of microRNAs (miRNAs) activity hold much promise for cancer therapy, but for clinical applications, the effi cient delivery of miRNAs to tumor cells or tumor tissues remains a great challenge. In this work, microRNA-181b inhibitor (anti-miR-181b) is successfully condensed into polyethyleneimine (PEI)-modifi ed and folate receptor (FR)-targeted PEGylated gold nanocages (AuNCs). This delivery system is designated as anti-miR-181b/PTPAuNCs nanocomplexes (PTPAuNC-NPs), which begin with chemical modifi cation of AuNCs with SH-PEG 5000 -folic acid (SH-PEG 5000 -FA) and SH-PEG 5000 through a gold-sulfur bond, followed by conjugating PEI using lipoic acid as a linker. Finally anti-miR-181b is condensed via electrostatic interactions. In vitro and in vivo experiments show that PTPAuNC-NPs can effi ciently deliver anti-miR-181b into target sites to suppress tumor growth, and considerably decrease tumor volumes in SMMC-7721 tumor-bearing nude mice under near-infrared radiation. All these results suggest that PTPAuNC-NP gene delivery system with combination of gene therapy and photothermal therapy will be of great potential use in future cancer therapy.

show abstract

TIMP-3 Expression Associates with Malignant Behaviors and Predicts Favorable Survival in HCC

Cited by 35 publications

References 39 publications

Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease and hepatocellular carcinoma

Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease and hepatocellular carcinoma

Functional roles of circular RNAs during epithelial-to-mesenchymal transition

Folic‐Acid‐Mediated Functionalized Gold Nanocages for Targeted Delivery of Anti‐miR‐181b in Combination of Gene Therapy and Photothermal Therapy against Hepatocellular Carcinoma

Contact Info

Product

Resources

About