The strategy developed herein is thus a highly promising platform for an effective codelivery of miRNA-122 and 5-Fu with facile fabrication and great potential for the clinical translation toward HCC synergistic therapy.
This study demonstrates that mice with a targeted deletion of the Mir122a gene possess several key phenotypes of human liver diseases, which provides a rationale for the development of a unique therapy for the treatment of chronic liver disease and HCC.
Decreased intra-hepatic levels of miR-122 were observed in patients with hepatocellular carcinoma, suggesting a potential role of miR-122 in the development of HCC.
In addition, although miRNAs have many expression patterns, the high frequency expression miRNAs (miR-21, miR-199 and miR-122) might be more specific for the diagnosis of hepatocellular carcinoma.The sources of heterogeneity might be related to the number of miRNAs and the specimen types in meta-regression.
The pooled sensitivity and specificity for miR-122-5p to diagnose HCC were 0.60 [95% confidence interval (CI), 0.48-0.71] and 0.81 (95% CI, 0.70-0.89), respectively.
First, we assessed the levels of miRNA122a in normal human hepatocytes, a panel of hepatocellular carcinoma (HCC) cell lines and hepatocellular CSCs observing its significant downregulation in HCC and CSCs.
Our results show that inflammation-induced miR-122 downregulation in hepatitis contributes to carcinogenesis and suggest that increasing miR-122 may be an effective strategy for preventing HCC development in CHB patients.
We studied the effects of restoring miR122 expression in a distinctive cell line derived from human HCC-BCLC9 cells-with a solid stem-like cell profile, high tumor initiating ability and undetectable miR122 expression.
These findings show that SIRT6 and miR-122 negatively regulate each other to control various aspects of liver physiology and SIRT6-miR-122 correlation may serve as a biomarker for hepatocarcinoma prognosis.
Furthermore, we identified MEF2D as an authentic target of miR-122, the reduced expression of which in hepatocellular carcinoma may be responsible for MEF2D upregulation.
Transcriptome profiling data from additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets.
Disrupting expression of miR-122 can re-activate embryo-expressed adult-silenced genes, ultimately leading to the development of hepatocellular carcinoma (HCC).
These data suggest that C/EBPα and eEF1A1 may play opposing roles in Sp1-regulating miR-122 transcription, and the eEF1A1 upregulation accompanied by C/EBPα downregulation in HCC may switch the regulatory functions of Sp1 and led to reduced miR-122 transcription.
Taken together, our findings demonstrated that combination of Ad-miR122 with chemotherapeutic agents inhibited HCC cell growth by inducing G2/M arrest and that this arrest is associated, at least in part, with reduced expression of MDR related genes and Cyclin B1.
These findings reveal critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeutic implications, including the potential utility of miR-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR-122 inhibition therapy for HCV.
Thus, this study revealed that the dysregulated glucose metabolism contributes to doxorubicin resistance, and the inhibition of glycolysis induced by miR-122 might be a promising therapeutic strategy to overcome doxorubicin resistance in hepatocellular carcinoma.
MicroRNA (miRNA) exert a profound effect on Hepatitis C virus (HCV) replication and on the manifestation of HCV-associated hepatocellular carcinoma (HCC). miR-122 in particular, is highly enriched in liver and has been shown to interact with HCV, suggesting this virus has evolved to subvert and manipulate the host gene silencing machinery in order to support its life cycle.