Your browser doesn't support javascript.
loading
MicroRNA-6838-5p suppresses the self-renewal and metastasis of human liver cancer stem cells through downregulating CBX4 expression and inactivating ERK signaling.
Dou, Zhimin; Lu, Fei; Hu, Jinjing; Wang, Haiping; Li, Bin; Li, Xun.
Afiliação
  • Dou Z; Department of the First Clinical Medical College, Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, Gansu, 730000, China.
  • Lu F; Department of Critical Care Medicine, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, Gansu, 730000, China.
  • Hu J; Department of the First Clinical Medical College, Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, Gansu, 730000, China.
  • Wang H; Department of Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, Gansu, 730000, China.
  • Li B; Department of Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, Gansu, 730000, China.
  • Li X; Department of Critical Care Medicine, The First Hospital of Lanzhou University, No.1, Donggang West Road, Chengguan District, Lanzhou, Gansu, 730000, China.
Biol Chem ; 404(1): 29-39, 2023 01 27.
Article em En | MEDLINE | ID: mdl-36215729
Hepatocellular carcinoma (HCC) is the most common primary human liver malignancy with high mortality. Liver cancer stem cells (CSCs) have been demonstrated to contribute to the recurrence, metastasis and drug resistance of liver cancer. Human HCC cohort analysis indicated that the epigenetic regulator polycomb chromobox homologue 4 (CBX4) was overexpressed in human HCC. Moreover, we found that CBX4 expression was significantly higher in CD44+ CD133+ Hep3B CSCs. Functionally, we demonstrated that CBX4 regulated cell proliferation, self-renewal, and metastasis ability of Hep3B CSCs. Bioinformatics analysis predicted that CBX4 was a direct target of microRNA-6838-5p (miR-6838-5p), which was further confirmed by luciferase reporter assay. MiR-6838-6p was down-regulated in HCC tumors and overexpression of miR-6838-5p attenuated the malignant traits of human liver CSCs in vitro. In addition, we found that miR-6838-5p/CBX4 axis modulates the biological properties of human liver CSCs via regulating ERK signaling. Overexpression of miR-6838-5p suppressed Hep3B xenograft tumor growth in vivo, while CBX4 overexpression abrogated the suppression effect, restored the angiogenesis, epithelial-to-mesenchymal transition (EMT), and ERK signaling in Hep3B tumor. In summary, our findings suggest that miR-6838-5p/CBX4 axis regulates liver tumor development and metastasis, which could be utilized as potential therapeutic target for HCC treatment.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / MicroRNAs / Neoplasias Hepáticas Tipo de estudo: Observational_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / MicroRNAs / Neoplasias Hepáticas Tipo de estudo: Observational_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article