Table 2 summarizes the miRNAs reported in the metastatic potential of HCC. The prognostication of HCC patients remains a major challenge for clinicians, and emerging evidence indicates that the outcome varies with underlying molecular pathology.78 To this end, profiling of miRNA expression have been informative in cancer risk prediction, diagnosis, prognosis, and responses to therapy.79–82

Polymorphisms in miRNAs and their targets have proved useful in predicting cancer risk. For instance, a G>C polymorphism in miR-146a precursor (rs2910164) predicted HCC development.80 This polymorphism located in the stem region opposite the mature miR-146a resulted in a change from G : U pair to C : U mismatch. Male individuals with GG genotype were twofold more susceptible www.selleckchem.com/products/crenolanib-cp-868596.html to HCC compared with those with CC genotype. In this context, the G-allelic miR-146a precursor displayed an increased production of mature miR-146a than the C-allelic one. Further investigations revealed that miR-146a significantly promoted cell proliferation and colony formation in NIH/3T3 cells.80 Another study also reported that polymorphisms present in the 3′-UTRs of mRNAs could affect miRNA binding. A polymorphism with insertion of ‘TTCA’ in the 3′UTR of interleukin-1 alpha (IL1A) (rs3783553) disrupted miR-122 and miR-378 binding, resulting in an increased expression of IL1A.81

The presence of this polymorphism likely contributed to HCC susceptibility as IL1A affects tumor growth, invasiveness, Selleckchem AZD8055 Molecular motor and also the interactions between malignant cells and the host’s immune system.81 Hepatocellular carcinoma tissues secrete various tumor-related proteins into the blood, and these may serve as circulating biomarkers for early diagnosis of HCC. Although serum

alpha fetoprotein (AFP) is widely used as a biomarker for HCC, recent research proposed new molecular biomarkers that are more specific.78 Serum miR-500 level has been shown to be commonly elevated in HCC patients and values returned to normal after surgical treatment.82 Certain miRNAs are associated with HCC subtypes, implying their potential in patient stratification for prognosis. Apart from the 20-miRNA metastasis signature that was shown to be associated with patient survival,44 another study demonstrated a set of 19-miRNAs correlated with HCC disease outcome.32 Proteins involved in cell cycle progression have been predicted to be targets of this 19-miRNA signature.32 It is also noteworthy that upregulation of the miR-221-222 cluster38,47 and downregulation of miR-26,83 miR-29,57 miR-12284 and miR-125b31 have been validated in independent studies to be associated with poor prognosis and shorter disease-free survival of HCC patients. Aside from their clinical usefulness as diagnostic and prognostic markers, miRNAs have also been shown to influence sensitivity of tumors to chemotherapeutic drugs.