Spermine synthase engages in macrophages M2 polarization to sabotage antitumor immunity in hepatocellular carcinoma.

Disturbances in tumor cell metabolism reshape the tumor microenvironment (TME) and impair antitumor immunity, but the implicit mechanisms remain elusive. Here, we found that spermine synthase (SMS) was significantly upregulated in tumor cells, which correlated positively with the immunosuppressive microenvironment and predicted poor survival in hepatocellular carcinoma (HCC) patients. Via "subcutaneous" and "orthotopic" HCC syngeneic mouse models and a series of in vitro coculture experiments, we identified elevated SMS levels in HCC cells played a role in immune escape mainly through its metabolic product spermine, which induced M2 polarization of tumor-associated macrophages (TAMs) and subsequently corresponded with a decreased antitumor functionality of CD8 T cells.

Radiation-sensitive circRNA hsa_circ_0096498 inhibits radiation-induced liver fibrosis by suppressing EIF4A3 nuclear translocation to decrease CDC42 expression in hepatic stellate cells.

Background: Radiation-induced liver fibrosis (RILF) is a common manifestation of radiation-induced liver injury (RILI) and is caused primarily by activated hepatic stellate cells (HSCs). Circular RNAs (circRNAs) play critical roles in various diseases, but little is known about the function and mechanism of circRNAs in RILF.

Methods: RNA pull-down and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to screen binding proteins of hsa_circ_0096498 (circ96498).

An Acid-Activatable Fluorescent Probe for Sulfur Dioxide in Traditional Chinese Medicines and Living Cells.

Excessive sulfur dioxide (SO₂) disturbs physiology of lysosomes causing diseases and threatening human health. A fluorescent probe has been regarded as one of the most attractive approaches, which is compatible with living cells and possesses high sensitivity. However, most of fluorescent probes' reaction sites are activated before they reach the destination.

ALKBH5-mediated m A demethylation of TIRAP mRNA promotes radiation-induced liver fibrosis and decreases radiosensitivity of hepatocellular carcinoma.

Background: Radiation-induced hepatic stellate cell (HSC) activation promotes radiation-induced liver fibrosis (RILF), a complication for hepatocellular carcinoma (HCC) radiotherapy. The demethylase alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) decreases N6-methyladenylate methylation (m A) modification of RNA, while its role in regulating RILF pathogenesis and HCC radiosensitivity remains unknown.

Methods: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing (RNA-seq) were used to screen target genes regulated by ALKBH5.

Machine-learning algorithms based on personalized pathways for a novel predictive model for the diagnosis of hepatocellular carcinoma.

Background: At present, the diagnostic ability of hepatocellular carcinoma (HCC) based on serum alpha-fetoprotein level is limited. Finding markers that can effectively distinguish cancer and non-cancerous tissues is important for improving the diagnostic efficiency of HCC.

Results: In this study, we developed a predictive model for HCC diagnosis using personalized biological pathways combined with a machine learning algorithm based on regularized regression and carry out relevant examinations.

Upregulated long non‑coding RNA LincIN promotes tumor progression via the regulation of nuclear factor 90/microRNA‑7/HOXB13 in esophageal squamous cell carcinoma.

Long non‑coding RNA LincIN has been reported to be overexpressed and to be involved in the metastasis of breast cancer. However, the expression and role of LincIN in esophageal squamous cell carcinoma (ESCC) remain unsolved. In the present study, LincIN expression was examined in ESCC by RT‑qPCR, and the roles of LincIN in ESCC were determined using cell growth, migration and invasion assays.

Construction and analysis of macrophage infiltration related circRNA-miRNA-mRNA regulatory networks in hepatocellular carcinoma.

Background: Macrophage play a crucial role in regulating tumor progression. This study intended to investigate the circular RNA (circRNA) regulatory network associated with macrophage infiltration in hepatocellular carcinoma (HCC).

Methods: The immune cell fractions of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium were calculated by Estimation of the Proportion of Immune and Cancer cells algorithm.

Construction of a circRNA-miRNA-mRNA Network Related to Macrophage Infiltration in Hepatocellular Carcinoma.

Immune cells in the tumor microenvironment play a crucial role in regulating tumor progression. The circular RNA (circRNA) regulatory network involved in immune cell infiltration in hepatocellular carcinoma (HCC) remains largely unknown. In this study, the "estimate the proportion of immune and cancer cells" (EPIC) application is used to evaluate the fractions of immune cells, cancer-associated fibroblasts, and endothelial cells in HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.

ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma.

Background: Radioimmunotherapy has a promising antitumor effect in hepatocellular carcinoma (HCC), depending on the regulatory effect of radiotherapy on tumor immune microenvironment. Ionizing radiation (IR)-induced DNA damage repair (DDR) pathway activation leads to the inhibition of immune microenvironment, thus impairing the antitumor effect of radioimmunotherapy. However, it is unclear whether inhibition of the DDR pathway can enhance the effect of radioimmunotherapy.

Interleukin 37 Suppresses M1 Macrophage Polarization Through Inhibition of the Notch1 and Nuclear Factor Kappa B Pathways.

Macrophage-orchestrated chronic inflammation plays an important role in cardiovascular disease, including accelerating the development of calcific aortic valve disease (CAVD). M1 and M2 macrophage polarization imbalances can alter intensity of inflammatory responses. Recombinant human interleukin 37 (IL-37) could be involved in regulating immune cell function to attenuate inflammation.