An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches

Abstract

Hepatocellular carcinoma (HCC) constitutes a frequent highly malignant form of primary liver cancer and is the third cause of death attributable to malignancy. Despite the improvement in the therapeutic strategies with the exploration of novel pharmacological agents, the survival rate for HCC is still low. Shedding light on the multiplex genetic and epigenetic background of HCC, such as on the emerging role of microRNAs, is considered quite promising for the diagnosis and the prediction of this malignancy, as well as for combatting drug resistance. MicroRNAs (miRNAs) constitute small noncoding RNA sequences, which play a key role in the regulation of several signaling and metabolic pathways, as well as of pivotal cellular functions such as autophagy, apoptosis, and cell proliferation. It is also demonstrated that miRNAs are significantly implicated in carcinogenesis, either acting as tumor suppressors or oncomiRs, while aberrations in their expression levels are closely associated with tumor growth and progression, as well as with local invasion and metastatic dissemination. The arising role of miRNAs in HCC is in the spotlight of the current scientific research, aiming at the development of novel therapeutic perspectives. In this review, we will shed light on the emerging role of miRNAs in HCC.

CENPB promotes the proliferation of hepatocellular carcinoma and is directly regulated by miR-29a

“…The imbalance in the expression of miRNAs has been proven to have a significant impact on diverse signaling pathways and mechanisms underlying many cancers [ 37 , 38 ]. More than half of the miRNAs found in the human genome are situated in genomic regions associated with cancer, and they contribute to the development of tumors either as tumor suppressors or oncogenes [ 39 ].…”

Genetic Alchemy unveiled: MicroRNA-mediated gene therapy as the Artisan craft in the battlefront against hepatocellular carcinoma—a comprehensive chronicle of strategies and innovations

“…Furthermore, the mRNA’s 3′-untranslated region (3′UTR) is targeted explicitly by miRNA-RISC (miRISC), which finds and binds to an mRNA strand that is only partly complementary. Crucial to this process is the miRNA seed sequence, which profoundly affects the interaction of miRNAs with mRNA ( Jungers and Djuranovic, 2022 ; Koustas et al, 2023 ).…”

Role of Non-Coding RNAs in Hepatocellular Carcinoma Progression: From Classic to Novel Clinicopathogenetic Implications

“…At the same time, by similarly acting, specific related lncRNAs and sncRNAs have been demonstrated to be actively involved in cancer-related chemoresistance processes, representing potential tools to optimize therapeutic approaches even in HCC management [72]. Based on this, in the last few decades, various encouraging results have emerged from the dramatic amount of research exploring potential ncRNA HCC-therapeutic targets [182,183].…”

“…Regarding miRNAs as potential therapeutic targets in HCC, as reported in previous paragraphs, these ncRNAs play a not-unidirectional role in cancerogenesis, considering the context of oncomiRs and TS-miRs simultaneously functioning in liver cancer. In light of this, if we consider that miRNA expression levels can be either inhibited or enhanced to achieve tumor suppression, the therapeutic potentialities of the modulation of these molecules appear even more interesting than siRNAs, whose unique philosophy of action is silencing and inhibiting specific molecules [181,182].…”