MicroRNA as Key Players in Hepatocellular Carcinoma: Insights into Their Role in Metastasis.

Liver cancer or hepatocellular carcinoma (HCC) remains the most common cancer in global epidemiology. Both the frequency and fatality of this malignancy have shown an upward trend over recent decades. Liver cancer is a significant concern due to its propensity for both intrahepatic and extrahepatic metastasis. Liver cancer metastasis is a multifaceted process characterized by cell detachment from the bulk tumor, modulation of cellular motility and invasiveness, enhanced proliferation, avoidance of the immune system, and spread either via lymphatic or blood vessels. MicroRNAs (miRNAs) are small non-coding ribonucleic acids (RNAs) playing a crucial function in the intricate mechanisms of tumor metastasis. A number of miRNAs can either increase or reduce metastasis via several mechanisms, such as control of motility, proliferation, attack by the immune system, cancer stem cell properties, altering the microenvironment, and the epithelial-mesenchymal transition (EMT). Besides, two other types of non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) can competitively bind to endogenous miRNAs. This competition results in the impaired ability of the miRNAs to inhibit the expression of the specific messenger RNAs (mRNAs) that are targeted. Increasing evidence has shown that the regulatory axis comprising circRNA/lncRNA-miRNA-mRNA is correlated with the regulation of HCC metastasis. This review seeks to present a thorough summary of recent research on miRNAs in HCC, and their roles in the cellular processes of EMT, invasion and migration, as well as the metastasis of malignant cells. Finally, we discuss the function of the lncRNA/circRNA-miRNA-mRNA network as a crucial modulator of carcinogenesis and the regulation of signaling pathways or genes that are relevant to the metastasis of HCC. These findings have the potential to offer valuable insight into the discovery of novel therapeutic approaches for management of liver cancer metastasis.