Non-coding RNAs as key regulators in hepatitis B virus-related hepatocellular carcinoma

Abstract

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a significant global health challenge due to its high prevalence and poor prognosis. Recent advances have revealed that non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs, circular RNAs, and small nucleolar RNAs, play critical regulatory roles in HBV-induced oncogenesis. These ncRNAs modulate various cancer hallmarks and contribute to HCC progression. Notably, their stability, detectability in bodily fluids, and disease-specific expression patterns render these ncRNAs as highly promising diagnostic and prognostic biomarkers for HBV-HCC. Herein, we review the types and mechanisms of HBV-related ncRNAs, emphasizing their dual roles as oncogenes and tumor suppressors. Furthermore, we discuss their applicability as diagnostic markers and therapeutic targets and review recent directions in ncRNA-based approaches that aim to enhance patient treatment. Concerning these aspects, the present review aimed to provide an understanding of the complexity of ncRNAs in HBV-related HCC with the hope of directing future research and developments towards effective control of this complex malignancy known as HCC.

Keywords: biomarkers; hepatitis B virus; hepatocellular carcinoma; non-coding RNAs; therapeutic targets.

Figure 1

ncRNAs in HBV-related HCC involved in cancer progression. ncRNAs such as the lncRNAs, miRNAs, and circRNAs involved in various mechanism including apoptosis, proliferation, immune evasion, tumor promoting inflammation, etc.

Figure 2

Aberrant expression of ncRNAs in HBV-related hepatocellular carcinoma has been observed. Different types of ncRNAs, including lncRNAs, miRNAs, and circRNAs, exhibit altered levels in HCC and interact with various proteins, influencing multiple signaling pathways such as MAPK, PI3K/Akt, NF-κB, Wnt/β-catenin, JAK-STAT, and TP53. Also, via regulating these pathways, the ncRNAs mechanistically regulates multiple mechanisms in HBV associated HCC including proliferation, invasion, metastasis, apoptosis, chromatin remodeling, immune evasion, EMT transition, cancer stem cell properties, angiogenesis and metabolic reprogramming of energy and glucose metabolism respectively.

Figure 3

Application of ncRNAs in HBV-related HCC were highlighted. Identification of prognostic biomarkers (lncRNAs, miRNAs, circRNAs) from the HBV-related HCC biopsy samples aid in the development of personalized medicine. Treatment modalities such as the Antisense oligonucleotides (ASO), miRNA mimics and inhibitors, small molecule inhibitors towards ncRNAs can be used to combat the disease progression. Considerable challenges and possible approaches towards ncRNAs therapeutics development were also highlighted.