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.
MiR-122 was reduced in hepatocarcinoma tissues compared to the para-carcinoma tissues, which was relatively low or high in hepatocarcinoma cell line SMMC7721 or Hep3B, and over-expressed miR-122 inhibited proliferation, migration or invasion in hepatocarcinoma cells.
Hepatocellular carcinoma-bearing mice were injected intratumorally with microRNA-122 (miR-122) mimics and an miR-122 negative control in the treatment and control groups, respectively.
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.
However, the expression level of miR-122 in blood did not have the ability in predicting OS (HR = 0.75, 95% CI 0.44-1.28, P = .29) and PFS (HR = 0.84, 95% CI 0.58-1.20, P = .33) of HCC.
In addition, the combination of the miRNA-122 and a fetoprotein may further improve the diagnostic accuracy between the HCC and healthy groups (area under the curve, 0.980; 95% confidence interval, 0.958-1.000).
In this work, with the use of newly developed PEGylated biodegradable charged polyester-based vectors (PEG-BCPVs) as the carrier, the miR26a and miR122 codelivering therapeutic strategy (PEG-BCPVs/miR26a/miR122 as the delivery formulation) is successfully developed for efficient treatment of human hepatocellular carcinoma (HCC).
In an HCC rat model, high miR-122 levels were associated with negative SerpinB3 expression, while low miR-122 levels correlated with SerpinB3 positivity.
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.
Disrupting expression of miR-122 can re-activate embryo-expressed adult-silenced genes, ultimately leading to the development of hepatocellular carcinoma (HCC).
And the combination of miR-122, miR-148a, and AFP increased the AUC to 0.931 (95% CI, 0.857-0.973), which can also be applied for distinguishing early HCC from LC. miR-122 was the best for differentiating HCC from NC (AUC: 0.990, 95% CI, 0.945-1.000).
Based on our analysis of fold-change in gene expression as a function of disease stage (i.e., early vs. advanced), coupled with consideration of the known relevant functions of these genes, we focused on four candidate genes, ACSL4, GNMT, IFI27, and miR122, which are expressed stage-specifically in HCV mono- and HIV-1/HCV co-infective liver disease and are known to play a pivotal role in regulating HCV-mediated hepatocellular carcinoma (HCC).