Long non-coding RNA in the regulation of cell death in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer, accounting for 90% of all cases. Currently, early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection, B-ultrasound, and computed tomography scanning; however, their specificity and sensitivity are suboptimal. Despite significant advancements in HCC biomarker detection, the prognosis for patients with HCC remains unfavorable due to tumor heterogeneity and limited understanding of its pathogenesis. Therefore, it is crucial to explore more sensitive HCC biomarkers for improved diagnosis, monitoring, and management of the disease. Long non-coding RNA (lncRNA) serves as an auxiliary carrier of genetic information and also plays diverse intricate regulatory roles that greatly contribute to genome complexity. Moreover, investigating gene expression regulation networks from the perspective of lncRNA may provide insights into the diagnosis and prognosis of HCC. We searched the PubMed database for literature, comprehensively classified regulated cell death mechanisms and systematically reviewed research progress on lncRNA-mediated cell death pathways in HCC cells. Furthermore, we prospectively summarize its potential implications in diagnosing and treating HCC.

Keywords: Apoptosis; Autophagy; Cell death; Hepatocellular carcinoma; Iron death; Long non-coding RNA; Necrosis.

Figure 1

Effect of aberrantly expressed long non-coding RNAs on cell death in different modes. A: H19 promotes the phosphorylation of MLKL by RIPK 3 through the miR-675 pathway, and MLKL forms a complex and translocates to the plasma membrane, ultimately leading to necroptosis; B: SNHG 11 binds miR-184 and targets AGO2; Caspase 3 expression increases and promotes apoptosis; C: HEPFAl promotes ferroptosis by modifying SLC7A11 ubiquitination; D: SNHG7 inhibits NLRP3-dependent pyroptosis by targeting the miR-34a/SIRT1 axis in liver cancer; E: NBR2 inhibits autophagy-induced cell proliferation through the ERK and JNK pathways; F: CDKN2A involved in the MAPK signaling pathway. LncRNAs: Long non-coding RNA.

Figure 2

Functional mechanisms of long non-coding RNA in hepatocellular carcinoma. A: UHRF1 drives hepatocellular carcinoma by inducing global DNA hypomethylation; B: Long non-coding RNAs (lncRNAs) bind to mRNAs and miRNAs to regulate their stability, thereby regulating gene expression; C: LncRNAs interact with proteins to regulate their stability or facilitate the formation of protein complex; D: Several lncRNAs hold the potential to encode small peptides, through which they exhibit their biological functions. lncRNAs: Long non-coding RNA.