In conclusion, the elevation of miR-34a and miR-224 may be associated with both benign and malignant proliferative processes, nevertheless the increased expression of oncomiRs miR-21 and miR-222 in cirrhosis and HCC but not in FNH may be related to malignant processes of the liver.
Serum exosomal miR-224 did have some ability to differentiate patients with HCC from healthy controls, with an area under the curve of 0.910, and HCC patients with higher serum exosomal miR-224 expression had lower overall survival.
Some serum/plasma miRNAs, including miR-21, miR-122, mi-125a/b, miR-199a/b, miR-221, miR-222, miR-223, miR-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of miRNAs have been obtained.
Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, Transwell migration, and Matrigel invasion assays were performed to clarify the molecular mechanism of miR-224 in the regulation of cell migration and invasion in human hepatocellular carcinoma (HCC).
In conclusion, the featured miRNAs (the upregulated miRNA‑224 and downregulated miRNA‑214) and their target genes are significant in the occurrence and development of HCC, which is likely to be significant for the identification of therapeutic targets and biomarkers to aid in the treatment of HCC.
Based on this finding, we further demonstrated that in hepatitis B virus (HBV)-related HCC, aberrant autophagy (low autophagic activity) results in accumulation of MIR224 and decreased expression of the target gene Smad4, which leads to increased cell migration and tumor formation.
In this study we determined that autophagy is down-regulated and inversely correlated with miR-224 expression in hepatitis B virus (HBV)-associated HCC patient specimens.
Among these, miR-224 was the most significantly uprgulated in HCC tissues (n = 18), compared with normal (n = 9) and HCC adjacent non-tumorous liver tissues (n = 18).
Furthermore, different elements consistently suggested that RKIP may be a target repressed by miR-224, a miRNA that is frequently and specifically upregulated in HCC, but our results excluded that this occurs, at least in the HCC cell lines.
We will discuss the validated and predicted functional roles of this miRNA in HCC, speculate on the possible mechanism for its upregulation in HCC and explore the potential of miR-224 as an exciting novel biomarker for the early detection of liver malignancies as well as a novel therapeutic target for HCC treatment.