Non-alcoholic fatty liver disease and hepatocellular carcinoma: Clinical challenges of an intriguing link

Figure 1 The molecular pathways that regulate non-alcoholic fatty liver disease-related hepatocellular carcinoma along with their interactions are represented. Activation of downstream signaling pathways is indicated by full or dot lines whereas inhibition of them is indicated by blunted lines with a circular-shaped “X”. Bidirectional arrows highlight the interplay between distinct molecular pathways. Molecules acting as mediators of signaling paths are indicated over a full, dot or blunted line in a box along with their names. MicroRNAs that promote hepatocellular carcinoma development are collectively represented in the upper left of the figure while tumor suppressor microRNAs are represented in the lower left of the schema. Cas: Caspase; DCA: Deoxycholic acid; ER: Endoplasmic reticulum; FFAs: Free fatty acids; HCC: Hepatocellular carcinoma; HDAC8: Histone deacetylase 8; HSCs: Hepatic stellate cells; IGF: Insulin growth factor; IL-6: Interleukin-6; IRec: Insulin receptor; IRes: Insulin resistance; JNK: Jun-(N)-terminal kinase; KC: Kuppfer cell; lncRNAs: Long non-coding RNAs; LPS: Lipopolysaccharides; MAPK: Mitogen-activated protein kinase; PAMPs: Pathogen-associated molecular patterns; SASP: Senescence associated secretory phenotype; STAT3: Signal transducer and activator of transcription 3; TGF-B: Transforming growth factor-B; TLR: Toll-liκe receptor.