Transmembrane 4 L Six Family Member 5 (TM4SF5)-Mediated Epithelial–Mesenchymal Transition in Liver Diseases

Author(s):  
Jung Weon Lee
Author(s):  
Shurong Ren ◽  
Qizhen Yue ◽  
Qiubo Wang ◽  
Yanli Zhang ◽  
Bei Zhang

Background: Chronic liver damages from viral infection or alcohol abuse result in liver fibrosis, which is a key pathological event in many types of liver diseases. Discovering new anti-fibrosis agents may provide alternative solutions to manage chronic liver diseases. Methods: We first used CCl4 induced liver fibrosis animal model to evaluate the beneficial effects of Cryptotanshinone (CRY). We next explored target miRNAs regulated by CRY in hepatocytes using microarray. The target miRNA candidate was confirmed with realtime-PCR. We also elucidated the downstream target and pathway directly regulated by the miRNA using luciferase assay, western blotting and Epithelial–Mesenchymal Transition (EMT) markers quantification. Lastly, we confirmed CRY induced expression changes of the target genes in vivo. Results: CRY oral administration markedly alleviated the liver injury caused by CCl4. miRNAs expression profiling and realtime-PCR validation revealed miR-539-3p was directly induced by CRY around 4 folds. The induction of miR-539-3p suppressed SMO expression and antagonized Hedgehog (Hh) pathway. Independently CRY treatment suppressed SMO and inhibited EMT process in hepatocytes. The CRY induced expression changes of both miR-539-3p (~ 2 folds increase) and SMO (~ 60% decrease) in livers were validated in animal model. Conclusion: Our study supported CRY could inhibit liver fibrosis by targeting Hh pathway during EMT. CRY could be used as anti-fibrosis agent candidate for managing chronic liver damages.


2021 ◽  
Vol 11 ◽  
Author(s):  
Suzhen Wang ◽  
Tianning Yang ◽  
Zhengxiang He

BackgroundThe involvement of microRNA-338-5p in modulating NPC pathogenesis is still largely unknown, and this study aimed to investigate this issue.MethodsThe expressions of cancer associated genes were determined by Real-Time qPCR and Western Blot, and cell apoptosis was determined by flow cytometer (FCM). CCK-8 assay and colony formation assay were respectively used to determine cell proliferation and colony formation abilities. Transwell assay was used to evaluate cell migration. The expression levels of Ki67 protein in mice tissues were measured by Immunohistochemistry (IHC) assay.ResultsThe present study found that microRNA-338-5p suppressed NPC progression by degrading its downstream target, Wnt family member 2B (WNT2B). Specifically, microRNA-338-5p tended to be low-expressed in NPC tissues and cell lines, compared to the non-tumor nasopharyngeal mucosa tissues and normal nasopharyngeal cell line (NP69). Upregulation of microRNA-338-5p inhibited proliferation, mobility, and epithelial-mesenchymal transition (EMT) in NPC cells in vitro, while silencing of microRNA-338-5p had opposite effects. Consistently, microRNA-338-5p suppressed tumorigenesis of NPC cells in vivo. In addition, microRNA-338-5p targeted WNT2B for degradation and inhibition, and the inhibiting effects of microRNA-338-5p overexpression on NPC development were reversed by upregulating WNT2B.ConclusionsTaken together, we concluded that microRNA-338-5p targeted WNT2B to hinder NPC development.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Zhao ◽  
Ronghang Li ◽  
Qian Wang ◽  
Minfei Wu ◽  
Yanbing Wang

Abstract Background Carboxypeptidase X, M14 family member 2 (CPXM2), has been associated with several human developmental disorders. However, whether CPXM2 is involved in oncogenesis or tumor progression remains unclear. Currently, the clinical relevance and function of CPXM2 in human osteosarcoma were investigated. Materials and methods The expression of CPXM2 in osteosarcoma cell lines and tissues were explored by immunohistochemistry and western blotting assays. A eukaryotic expression plasmid was transfected into fetal osteoblast cells to overexpress CPXM2 and the endogenous CPXM2 in osteosarcoma cells was silenced through an RNA interference (RNAi) method transfection. These transfections were validated via western blotting, and the expression levels of several key molecules involved in the epithelial mesenchymal transition was also determined via western blotting. The expression levels of CPXM2 in a fetal osteoblast cell line with CPXM2 overexpressing and an osteosarcoma CPXM2-knockout cell line was confirmed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunofluorescence. The malignant phenotype of osteosarcoma cells was indicated by the cholecystokinin octapeptide, colony formation assay, scratch wound healing assay, and Transwell® migration assay. Results We found that CPXM2 was overexpressed in osteosarcoma and that the overexpression was associated with an unfavorable prognosis and tumor node metastasis staging. The knockdown of CPXM2 in cultured osteosarcoma cells significantly impeded cell proliferation and migration. In addition, the upregulation of CPXM2 in fetal osteoblast cells significantly promoted cell proliferation and migration. Besides, western blotting results revealed that several key molecules involved in the epithelial mesenchymal transition (EMT) were regulated by CPXM2. Conclusion Taken together, these results imply an active role for CPXM2 in promoting tumor aggressiveness via epithelial to mesenchymal transition (EMT) modulation in osteosarcoma.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7073
Author(s):  
Guangyi Jiang ◽  
Chiung-Kuei Huang ◽  
Xinjie Zhang ◽  
Xingyu Lv ◽  
Yifan Wang ◽  
...  

Background The Wnt signaling pathway, an evolutionarily conserved molecular transduction cascade, has been identified as playing a pivotal role in various physiological and pathological processes of the liver, including homeostasis, regeneration, cirrhosis, and hepatocellular carcinoma (HCC). In this study, we aimed to use a bibliometric method to evaluate the emerging trends on Wnt signaling in liver diseases. Methods Articles were retrieved from the Web of Science Core Collection. We used a bibliometric software, CiteSpace V 5.3.R4, to analyze the active countries or institutions in the research field, the landmark manuscripts, important subtopics, and evolution of scientific ideas. Results In total, 1,768 manuscripts were published, and each was cited 33.12 times on average. The U.S. published most of the articles, and the most active center was the University of Pittsburgh. The top 5 landmark papers were identified by four bibliometric indexes including citation, burstness, centrality, and usage 2013. The clustering process divided the whole area into nine research subtopics, and the two major important subtopics were “liver zonation” and “HCC.” Using the “Part-of-Speech” technique, 1,743 terms representing scientific ideas were identified. After 2008, the bursting phrases were “liver development,” “progenitor cells,” “hepatic stellate cells,” “liver regeneration,” “liver fibrosis,” “epithelial-mesenchymal transition,” and etc. Conclusion Using bibliometric methods, we quantitatively summarized the advancements and emerging trends in Wnt signaling in liver diseases. These bibliometric findings may pioneer the future direction of this field in the next few years, and further studies are needed.


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