The mechanisms of renin–angiotensin system in hepatocellular carcinoma: From the perspective of liver fibrosis, HCC cell proliferation, metastasis and angiogenesis, and corresponding protection measures

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, of which the occurrence and development involve a variety of pathophysiological processes, such as liver fibrosis, hepatocellular malignant proliferation, metastasis, and tumor angiogenesis. Some important cytokines, such as TGF-β, PI3K, protein kinase B (Akt), VEGF and NF-κB, can regulate the growth, proliferation, diffusion, metastasis, and apoptosis of HCC cells by acting on the corresponding signaling pathways. Besides, many studies have shown that the formation of HCC is closely related to the main components of renin-angiotensin system (RAS), such as Ang II, ACE, ACE2, MasR, AT1R, and AT2R. Therefore, this review focused on liver fibrosis, HCC cell proliferation, metastasis, tumor angiogenesis, and corresponding protective measures. ACE-Ang II-AT1 axis and ACE2-Ang-(1−7)-MasR axis were taken as the main lines to introduce the mechanism of RAS in the occurrence and development of HCC, so as to provide references for future clinical work and scientific research. •RAS can influence the formation and progression of hepatocellular carcinoma (HCC).•Hepatic stellate cells activation, AT1R/TGF-β/Smad and AT1R/TGF-β/MAPK signaling pathways can aggravate the process of liver fibrosis.•Insulin resistance, AT1R/PI3K/Akt/mTOR and AT1R/Raf/ERK1/2 signaling pathways can promote the proliferation of HCC cells.•VEGF, NF-κB and MMP-9 can accelerate the process of angiogenesis and metastasis in HCC.•The protective effect of microRNAs, ACEI, ARB and ACE2/Ang-(1−7)/MasR signaling pathway on HCC.