Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, with high morbidity, relapse and mortality rates. Multipotent mesenchymal stromal cells (MSCs) can be recruited to and become integral components of the HCC microenvironment and can influence tumor progression. This review discusses MSC migration to liver fibrosis and the HCC microenvironment, MSC involvement in HCC initiation and progression and the widespread application of MSCs in HCC-targeted therapy, thus clarifying the critical roles of MSCs in HCC.

The advances in microfluidic technology have recently generated various microfluidic-based biomimetic models as novel three-dimensional (3D) models for life science research, offering some great advantages over conventional two-dimensional (2D) models, classical scaffold-free or scaffold-based 3D approaches and animal models. These biomimetic models could simulate the microenvironment of in vivo tissues and organs by controlling spatiotemporal gradients of chemical substances and imitating mechanical activities of living tissues and organs. They provide platforms for real-time observation of physiological and pathological processes, toxicology effect and drug effects in tissues and organs for life science research. Without a doubt, microfluidic-based biomimetic models would serve as a powerful tool for developing diagnosis and treatment methods for various diseases. In this study, we briefly summarized the fabrication of microfluidic-based biomimetic models and their use as 3D tissue/organ models.

Introduction: Hepatocellular carcinoma (HCC) is recognized as the prime and lethal form of liver cancer caused by the hepatitis B virus (HBV) and hepatitis C virus (HCV) globally. Lactate is an end product of glycolysis that influences epigenetic expression through histone lactylation. While MKI67 and RACGAP1 play crucial roles in HBV- and HCV-related HCC. However, the role of lactylation-related genes (LRGs) effects in this context remains unclear. This study innovatively explored the role of LRGs in HBV/HCV-associated HCC, identifying novel biomarkers for diagnosis and prognosis.Methods: The present study used various online databases for analysis, and the findings were validated via immunohistochemical (IHC) analysis of HCC patient samples (n=60).Results: We identified six signature LRGs (ALB, G6PD, HMGA1, MKI67, RACGAP1, and RFC4) possess prognostic potential, correlation with immune infiltration, and lactylation-related pathways, providing novel insights into tumor microenvironment (TME) of HCC. Moreover, MKI67 and RACGAP1 were significantly associated with HBV- and HCV-related HCC. IHC confirmed these findings, with high expression of MKI67 and RACGAP1 was significantly linked with HBV/HCV-associated HCC compared to non-viral HCC. The expression is also significantly associated with key clinical variables.Conclusion: Our results suggest that MKI67 and RACGAP1 could serve as promising biomarkers for detecting and predicting HCC caused by HBV/HCV via lactylation, opening a new direction for immune-targeted therapies.

The present study aimed to identify sensitive, specific and independent prognostic biomarkers in head and neck cancer (HNC) based on microRNA expression profiles and other high-throughput sequencing data in The Cancer Genome Atlas (TCGA) database. Identification of such prognostic biomarkers could provide insight into HNC diagnosis and treatment. The differential expression profiles of microRNAs between HNC tissues and adjacent cancer tissues in the TCGA database were analyzed (log fold-change >2; P<0.01). Univariate and multivariate Cox regression analyses of the differentially expressed microRNAs were performed to determine those significantly related to the survival of patients with HNC. The identified microRNAs were verified by survival and receiver operating characteristic curve analyses. To better predict prognosis, a combined prognostic model (risk equation) was established based on the risk coefficient of each microRNA, calculated by a multivariate Cox regression analysis, and the risk score was calculated. To explore the signaling pathways related to prognosis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on the differentially expressed genes between the high-risk and low-risk groups, grouped according to the median risk score. A total of 89 differentially expressed microRNAs between HNC and adjacent cancer tissues were screened, 11 of which were identified as risk factors related to HNC survival by the univariate Cox regression analysis (P<0.05). The multivariate Cox regression analysis showed that three of the 11 microRNAs, hsa-miR-99a, hsa-miR-499a and hsa-miR-1911 (all P<0.01), were identified as independent risk factors significantly related to patient survival. The risk equation used was as follows: Risk score=(-0.1597 x hsa-miR-99a) + (0.1871 x hsa-miR-499a) + (0.1033 x hsa-miR-1911). KEGG and GO analyses showed that the JAK-STAT signaling pathway and some metabolic pathways were associated with HNC prognosis. The present study suggested that hsa-miR-99a, hsa-miR-499a and hsa-miR-1911 may serve as potential prognostic biomarkers in HNC.

Purpose The study aimed to investigate the role of FBXW11 in hepatocellular carcinoma (HCC) and its underlying mechanism. Specifically, we explored whether FBXW11 inhibits tumorigenesis by regulating YB1 ubiquitination and elucidated the functional significance of the FBXW11-YB1 axis in HCC progression. Methods Clinical HCC specimens and cell lines (HCC-LM3, HuH7, Hep3B, SNU-449) were used. FBXW11 and YB1 expression were analyzed via Western blotting and immunohistochemistry (IHC). Gain- and loss-of-function assays (FBXW11 overexpression/knockdown) were performed to assess cell proliferation. Co-immunoprecipitation (Co-IP), mass spectrometry, and ubiquitination assays identified protein interactions and ubiquitination patterns. In vivo tumorigenesis was evaluated using xenograft models in nude mice. Correlations with clinicopathological features and survival were analyzed via statistical methods. Results FBXW11 was significantly downregulated in HCC tissues, correlated with advanced TNM stages and poor overall survival (HR = 3.058, P = 0.042). FBXW11 overexpression suppressed HCC cell proliferation, while knockdown enhanced it. Mechanistically, FBXW11 directly interacted with the cold shock domain (CSD) of YB1, promoting K48-linked polyubiquitination and proteasomal degradation of YB1. YB1 overexpression rescued the tumor-suppressive effects of FBXW11 overexpression. In vivo, FBXW11 overexpression inhibited tumor growth by suppressing the YB1/Akt/mTOR signaling pathway, which was rescued by YB1 re-expression. Conclusion FBXW11 acts as a tumor suppressor in HCC by mediating YB1 ubiquitination and degradation, thereby inhibiting the Akt/mTOR pathway. The FBXW11-YB1 axis represents a novel regulatory mechanism in hepatocarcinogenesis, highlighting FBXW11 as a potential prognostic biomarker and therapeutic target for HCC.