AI Article Synopsis
- Liver cancer stem cells (LCSCs) play a crucial role in the development and progression of hepatocellular carcinoma (HCC), and the function of the miRNA-302 family in LCSCs is not well understood.
- Research revealed that miRNA-302a/d is downregulated during HCC cell growth, and lower levels of these miRNAs are associated with shorter survival times in HCC patients, indicating their potential role as biomarkers.
- MiRNA-302a/d directly targets and inhibits the gene E2F7, affecting LCSCs' self-renewal and proliferation by regulating the AKT/β-catenin/CCND1 signaling pathway, suggesting a mechanism for how
Article Abstract
Background: There is increasing evidence that liver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) initiation and progression. MicroRNA (miRNA) plays a significant functional role by directly regulating respective targets in LCSCs-triggered HCC, however, little is known about the function of the miRNA-302 family in LCSCs.
Methods: MiRNAs microarray was used to detect the miRNAs involved in LCSCs maintenance and differentiation. Biological roles and the molecular mechanism of miRNA-302a/d and its target gene E2F7 were detected in HCC in vitro. The expression and correlation of miRNA-302a/d and E2F7 in HCC patients was evaluated by quantitative PCR and Kaplan-Meier survival analysis.
Results: We found that the miRNA-302 family was downregulated during the spheroid formation of HCC cells and patients with lower miRNA-302a/d expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, E2F7 was confirmed to be directly targeted and inhibited by miRNA-302a/d. Furthermore, concomitant low expression of miRNA-302a/d and high expression of E2F7 correlated with a shorter median OS and PFS in HCC patients. Cellular functional analysis demonstrated that miRNA-302a/d negatively regulates self-renewal capability and cell cycle entry of liver cancer stem cells via suppression of its target gene E2F7 and its downstream AKT/β-catenin/CCND1 signaling pathway.
Conclusions: Our data provide the first evidence that E2F7 is a direct target of miRNA-302a/d and miRNA-302a/d inhibits the stemness of LCSCs and proliferation of HCC cells by targeting the E2F7/AKT/β-catenin/CCND1 signaling pathway.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192354 | PMC |
| http://dx.doi.org/10.1186/s13046-018-0927-8 | DOI Listing |
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