Your browser doesn't support javascript.
loading
Antler-derived microRNA PC-5p-1090 inhibits HCC cell proliferation, migration, and invasion by targeting MARCKS, SMARCAD1, and SOX9.
Wu, Jin; Yang, Fan; Zhao, Mindie; Xiao, Hui; Chen, Yanxia; Liu, Xuedong; Zheng, Dong.
Afiliação
  • Wu J; Laboratory of Genetics and Molecular Biology, College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, China.
  • Yang F; Laboratory of Genetics and Molecular Biology, College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, China.
  • Zhao M; Laboratory of Genetics and Molecular Biology, College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, China.
  • Xiao H; Departments of Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215008, Jiangsu, China.
  • Chen Y; College of Ecology-Environment Engineering, Qinghai University, Xining, 810016, Qinghai, China.
  • Liu X; Laboratory of Genetics and Molecular Biology, College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, China. liuxuedong@nefu.edu.cn.
  • Zheng D; Laboratory of Genetics and Molecular Biology, College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, China. zhengdong89@yeah.net.
Funct Integr Genomics ; 23(2): 156, 2023 May 11.
Article em En | MEDLINE | ID: mdl-37165199
ABSTRACT
The capability of microRNAs (miRNAs) to regulate gene expression across species has opened new avenues for miRNA-based therapeutics. Here, we investigated the potential of PC-5p-1090 (miR-PC-1090), a miRNA found in deer antlers, to control the malignant phenotypes of hepatocellular carcinoma (HCC) cells. Using Cell Counting Kit-8 and transwell assays, we found that heterologous expression of miR-PC-1090 inhibited HCC cell proliferation, migration, and invasion. Bioinformatics analysis indicated that predicted miR-PC-1090 targets, including MARCKS, SMARCAD1, and SOX9, were significantly elevated in HCC tissues, and their high expressions were associated with poor overall survival of HCC patients. Moreover, mechanistic investigations revealed that miR-PC-1090 promoted the degradation of MARCKS and SMARCAD1 mRNAs and hindered the translation of SOX9 mRNA by recognizing their 3' untranslated regions. Subsequent loss-of-function and rescue experiments confirmed the involvement of MARCKS, SMARCAD1, and SOX9 in miR-PC-1090-suppressed HCC cell proliferation, migration, and invasion. Notably, MARCKS knockdown induced the downregulation of phosphorylated MARCKS and a corresponding upregulation of phosphorylated AKT in HCC. Conversely, miR-PC-1090 repressed MARCKS phosphorylation and effectively circumvented the activation of the PI3K/AKT pathway. Furthermore, miR-PC-1090 regulates the Wnt/ß-catenin pathway through SMARCAD1- and SOX9-mediated reduction of ß-catenin expression. Overall, our results illustrate the tumor-suppressive activity and molecular mechanism of antler-derived miR-PC-1090 in HCC cells, indicating its potential as a multiple-target agent for HCC treatment.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Chifres de Veado / Cervos / Carcinoma Hepatocelular / MicroRNAs / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Funct Integr Genomics Assunto da revista: BIOLOGIA MOLECULAR / GENETICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Chifres de Veado / Cervos / Carcinoma Hepatocelular / MicroRNAs / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Funct Integr Genomics Assunto da revista: BIOLOGIA MOLECULAR / GENETICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China