Guanghao Li

MicroRNAs (miRNAs) are small non-coding RNAs (18-26 nucleotides) that regulate gene expression by interacting with target mRNAs, affecting various physiological and pathological processes. miRTarBase, a database of experimentally validated miRNA-target interactions (MTIs), now features over 3 817 550 validated MTIs from 13 690 articles, significantly expanding its previous version. The updated database includes miRNA interactions with therapeutic agents, revealing roles in drug resistance and therapeutic strategies. It also highlights miRNAs as predictive, safety and monitoring biomarkers for toxicity assessment, clinical treatment guidance and therapeutic optimization. The expansion of miRNA-mRNA and miRNA-miRNA networks allows the identification of key regulatory genes and co-regulatory miRNAs, providing deeper insights into miRNA functions and critical target genes. Information on oxidized miRNA sequences has been added, shedding light on how oxidative modifications influence miRNA targeting and regulation. The integration of the LLAMA3 model into the NLP pipeline, alongside prompt engineering, enables the efficient identification of MTIs and miRNA-disease associations without large training datasets. An updated data integration and a redesigned user interface enhance accessibility, reinforcing miRTarBase as an essential resource for molecular oncology, drug development and related fields. The updated miRTarBase is available at https://mirtarbase.cuhk.edu.cn/∼miRTarBase/miRTarBase_2025.

Hepatitis B virus (HBV) infection is a major driver of hepatocarcinogenesis. Ferroptosis is a type of iron-mediated cell death that can suppress liver transformation. Previous studies have linked HBV to ferroptosis in liver fibrosis and acute liver failure. However, whether ferroptosis is involved in HBV-mediated liver cancer is poorly understood. Here, we identified heat shock protein family A member 8 (HSPA8) as a crucial host factor that modulates HBV replication and ferroptosis in liver cancer. Hepatitis B X protein (HBx) upregulated HSPA8 by coactivating the transcription factor heat shock factor 1 (HSF1) in cells. HSPA8 enhanced HBV replication by recruiting hepatitis B core protein (HBc) to the HBV covalently closed circular DNA (cccDNA) minichromosome, forming a positive feedback loop. Moreover, HSPA8 suppressed ferroptosis in liver cancer cells by upregulating the expression of SLC7A11/GPX4 and decreasing erastin-mediated reactive oxygen species and Fe2+ accumulation in cells in vitro and in vivo. Inhibition of HSPA8 reduced the growth of HBV-positive liver tumors and increased sensitivity to erastin. In conclusion, HBx-elevated HSPA8 regulates both HBV replication and ferroptosis in liver cancer. Targeting HSPA8 could be a promising strategy for controlling HBV and hepatocarcinogenesis. SIGNIFICANCE: HBV-induced upregulation of HSPA8 promotes hepatocarcinogenesis by suppressing ferroptosis and stimulating HBV replication, identifying HSPA8 as a potential therapeutic target in liver cancer.

‑independent immunoglobulin‑like cellular adhesion molecules (including Nectins 1‑4), involved in cell adhesion via homophilic/heterophilic interplay. In addition, the Nectin family plays a significant role in enhancing cellular viability and movement ability. In contrast to enrichment of Nectins 1‑3 in normal tissues, Nectin‑4 is particularly overexpressed in a number of tumor types, including breast, lung, urothelial, colorectal, pancreatic and ovarian cancer. Moreover, the upregulation of Nectin‑4 is an independent biomarker for overall survival in numerous cancer types. A large number of studies have revealed that high expression of Nectin‑4 is closely related to tumor occurrence and development in various cancer types, but the manner in which Nectin‑4 protein contributes to the onset and development of these malignancies is yet unknown. The present review summarizes the molecular mechanisms and functions of Nectin‑4 protein in the biological processes and current advances with regard to its expression and regulation in various cancer types.