MicroRNAs as Diagnostic Tools in Hepatocellular Carcinoma

Abstract

Liver cancer is the fourth leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of all liver cancers. The serum concentration of alpha-fetoprotein (AFP) is the only validated biomarker for HCC diagnosis. MicroRNAs (miRNAs) are small non-coding RNAs of 21–30 nucleotides playing a critical role in human carcinogenesis, with types of miRNAs with oncogenic (oncomiRs) or tumor suppressor features. The altered expression of miRNAs in HCC is associated with many pathological processes, such as cancer initiation, tumor growth, apoptosis escape, promotion of migration and invasion. Moreover, circulating miRNAs have been increasingly investigated as non-invasive biomarkers for HCC diagnosis. MiRNAs’ expression patterns are altered in HCC and several single miRNAs or miRNAs panels have been found significantly up or downregulated in HCC with respect to healthy controls or non-oncological patients (cirrhotic or with viral hepatitis). However, any of the investigated miRNAs or miRNAs panels has entered clinical practice so far. This has mostly to do with lack of protocols standardization, small sample size and discrepancies in the measurement techniques. This review summarizes the major findings regarding the diagnostic role of miRNAs in HCC and their possible use together with standard biomarkers in order to obtain an early diagnosis and easier differential diagnosis from non-cancerous liver disease.

MicroRNA-122 mimic/microRNA-221 inhibitor combination as a novel therapeutic tool against hepatocellular carcinoma

“…Multiple aberrantly expressed miRNAs were revealed to be implicated in hepatocarcinogenesis. For instance, miR-221 up-regulation has been shown to promote cell cycle progression, reduce apoptosis, favor angiogenesis, and confer cell migratory properties on HCC malignant cells [ 23 ]. One of the down-regulated miRNAs in liver cancer is the hepato-specific miR-122, which makes up about 70% of the miRNAs population in the adult liver and has a critical role in regulating the metabolism of fatty acids and cholesterol.…”

The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC

“…In contrast, few studies have investigated their implication in NAFLD-related HCC progression. Hence, specific hepatic miRNAs have been shown to regulate lipid metabolism, glucose homeostasis, cell proliferation, apoptosis, migration, and differentiation in NAFLD, HCC, or NAFLD-related HCC, thus being considered novel potential molecular biomarkers associated with these liver diseases [ 103 , 104 , 105 , 106 , 107 ].…”