{"title":"基于水凝胶的miR-192递送通过抑制GSK3β/Wnt/β-catenin途径抑制肝细胞癌的发展。","authors":"Qing Yang, Xiaojv Zhuge, Weili Lin, Weilai Yu, Yu Zhu, Changsheng Shi, Zhengchao Shi","doi":"10.4149/neo_2023_230317N150","DOIUrl":null,"url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by high invasiveness, metastasis, and poor prognosis, which lacks effective treatments. Although the role of miR-192 in HCC development has been recognized, the underlying molecular mechanism is still poorly understood. This study aimed to explore the impact of mir-192 on HCC and its potential as a therapeutic strategy. Wound healing assay, Transwell assay, CCK-8 assay, and flow cytometry were performed to detect the impact of miR-192 on HCC cell metastasis, invasion, proliferation, and apoptosis, respectively. q-PCR and western blot were applied to measure the relative mRNA and protein expression of the GSK3β/Wnt/β-catenin pathway in miR-192-overexpressing cell lines. Immunofluorescence was carried out to detect the nuclear translocation of β-catenin. starBase website and dual luciferase reporter assay were used to verify the interaction between miR-192 and the target gene WNT10B 3'-untranslated region (3'-UTR) of the Wnt pathway. In addition, we developed algin/polyethyleneimine@miR-192 (AG/PEI@miR-192) nanohydrogel for in vivo delivery of miR-192-agomir. The results revealed that overexpressed miR-192 reduced the expression of HCC cell surface markers CD90, EpCAM, and CD133. Moreover, miR-192 overexpression inhibited HCC cell metastasis, invasion, and proliferation, promoted cell apoptosis, and reduced GSK3β/Wnt/β-catenin pathway expression. Additionally, AG/PEI@miR-192 exhibited good drug release and tumor inhibition. In conclusion, our study suggested that miR-192 inhibits HCC development by suppressing the GSK3β/Wnt/β-catenin pathway and proposed a promising hydrogel-based miR-192 delivery approach to hinder tumor growth.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"555-565"},"PeriodicalIF":2.0000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hydrogel-based miR-192 delivery inhibits the development of hepatocellular carcinoma by suppressing the GSK3β/Wnt/β-catenin pathway.\",\"authors\":\"Qing Yang, Xiaojv Zhuge, Weili Lin, Weilai Yu, Yu Zhu, Changsheng Shi, Zhengchao Shi\",\"doi\":\"10.4149/neo_2023_230317N150\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by high invasiveness, metastasis, and poor prognosis, which lacks effective treatments. Although the role of miR-192 in HCC development has been recognized, the underlying molecular mechanism is still poorly understood. This study aimed to explore the impact of mir-192 on HCC and its potential as a therapeutic strategy. Wound healing assay, Transwell assay, CCK-8 assay, and flow cytometry were performed to detect the impact of miR-192 on HCC cell metastasis, invasion, proliferation, and apoptosis, respectively. q-PCR and western blot were applied to measure the relative mRNA and protein expression of the GSK3β/Wnt/β-catenin pathway in miR-192-overexpressing cell lines. Immunofluorescence was carried out to detect the nuclear translocation of β-catenin. starBase website and dual luciferase reporter assay were used to verify the interaction between miR-192 and the target gene WNT10B 3'-untranslated region (3'-UTR) of the Wnt pathway. In addition, we developed algin/polyethyleneimine@miR-192 (AG/PEI@miR-192) nanohydrogel for in vivo delivery of miR-192-agomir. The results revealed that overexpressed miR-192 reduced the expression of HCC cell surface markers CD90, EpCAM, and CD133. Moreover, miR-192 overexpression inhibited HCC cell metastasis, invasion, and proliferation, promoted cell apoptosis, and reduced GSK3β/Wnt/β-catenin pathway expression. Additionally, AG/PEI@miR-192 exhibited good drug release and tumor inhibition. In conclusion, our study suggested that miR-192 inhibits HCC development by suppressing the GSK3β/Wnt/β-catenin pathway and proposed a promising hydrogel-based miR-192 delivery approach to hinder tumor growth.</p>\",\"PeriodicalId\":19266,\"journal\":{\"name\":\"Neoplasma\",\"volume\":\"70 4\",\"pages\":\"555-565\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2023-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neoplasma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4149/neo_2023_230317N150\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neoplasma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4149/neo_2023_230317N150","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Hydrogel-based miR-192 delivery inhibits the development of hepatocellular carcinoma by suppressing the GSK3β/Wnt/β-catenin pathway.
Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by high invasiveness, metastasis, and poor prognosis, which lacks effective treatments. Although the role of miR-192 in HCC development has been recognized, the underlying molecular mechanism is still poorly understood. This study aimed to explore the impact of mir-192 on HCC and its potential as a therapeutic strategy. Wound healing assay, Transwell assay, CCK-8 assay, and flow cytometry were performed to detect the impact of miR-192 on HCC cell metastasis, invasion, proliferation, and apoptosis, respectively. q-PCR and western blot were applied to measure the relative mRNA and protein expression of the GSK3β/Wnt/β-catenin pathway in miR-192-overexpressing cell lines. Immunofluorescence was carried out to detect the nuclear translocation of β-catenin. starBase website and dual luciferase reporter assay were used to verify the interaction between miR-192 and the target gene WNT10B 3'-untranslated region (3'-UTR) of the Wnt pathway. In addition, we developed algin/polyethyleneimine@miR-192 (AG/PEI@miR-192) nanohydrogel for in vivo delivery of miR-192-agomir. The results revealed that overexpressed miR-192 reduced the expression of HCC cell surface markers CD90, EpCAM, and CD133. Moreover, miR-192 overexpression inhibited HCC cell metastasis, invasion, and proliferation, promoted cell apoptosis, and reduced GSK3β/Wnt/β-catenin pathway expression. Additionally, AG/PEI@miR-192 exhibited good drug release and tumor inhibition. In conclusion, our study suggested that miR-192 inhibits HCC development by suppressing the GSK3β/Wnt/β-catenin pathway and proposed a promising hydrogel-based miR-192 delivery approach to hinder tumor growth.