Non-coding RNAs in hepatocellular carcinoma: Insights into regulatory mechanisms, clinical significance, and therapeutic potential

Abstract

Hepatocellular carcinoma (HCC) is a complex and heterogeneous malignancy with high incidence and poor prognosis. In addition, owing to the lack of diagnostic and prognostic markers, current multimodal treatment options fail to achieve satisfactory outcomes. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transition (EMT), invasion, metastasis, metabolism, and drug resistance are important factors influencing tumor development and therapy. The intercellular communication of these important processes is mediated by a variety of bioactive molecules to regulate pathophysiological processes in recipient cells. Among these bioactive molecules, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), account for a large part of the human transcriptome, and their dysregulation affects the progression of HCC. The purpose of this review is to evaluate the potential regulatory mechanisms of ncRNAs in HCC, summarize novel biomarkers from somatic fluids (plasma/serum/urine), and explore the potential of some small-molecule modulators as drugs. Thus, through this review, we aim to contribute to a deeper understanding of the regulatory mechanisms, early diagnosis, prognosis, and precise treatment of HCC.

Circular RNA Circ_0001971 Aggravates the Progression of Hepatocellular Carcinoma Cells by Activating the miR-186-5p/KLF7

“…However, the specific mechanism of HCC development is still controversial, and most scholars believe that its development is highly correlated with circRNA [14]. circRNA is a special non-coding RNA [15], mainly involved in gene expression regulation at the transcriptional and post-transcriptional levels. By regulating the expression of downstream target genes, mirnas and proteins, CircrNA can affect the proliferation [16], migration, invasion and apoptosis of tumor cells, etc., thus affecting the occurrence and development of HCC.…”

MicroRNA-204-5p Inhibits Hepatocellular Carcinoma by Targeting the Regulator of G Protein Signaling 20

“…Noncoding RNA (regulatory ncRNAs) involved in the regulation of the same type of gene are known as miRNAs. There are two main types of ncRNAs: long noncoding RNAs (lncRNAs) and short noncoding RNAs (piRNAs, miRNAs, and siRNAs) . lncRNAs and miRNAs interact as competitive endogenous RNAs (ceRNAs), which allows the former to regulate the expression and biological functions of miRNAs .…”

“…There are two main types of ncRNAs: long noncoding RNAs (lncRNAs) and short noncoding RNAs (piRNAs, miRNAs, and siRNAs). 41 lncRNAs and miRNAs interact as competitive endogenous RNAs (ceRNAs), which allows the former to regulate the expression and biological functions of miRNAs. 42 Lu et al, discovered that the lncRNA HOTAIR targeted miR-204-5p in cholangiocarcinoma cells, thereby inhibiting apoptosis and autophagy and promoting cell proliferation.…”

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

“…Unlike sampling ncRNAs via invasive techniques such as biopsy, it is easy and inexpensive to detect ncRNAs from blood samples ( 119 ). However, the current obstacle is the lack of some ncRNAs with sensitivity and specificity ( 120 ).…”