Linc-ROR inhibits NK cell-killing activity by promoting RXRA ubiquitination and reducing MICB expression in gastric cancer patients.

Linc-ROR plays an important role in gastric cancer (GC) development and progression. This study sought to determine how the aberrant expression of Linc-ROR impacts GC progression and immune evasion, and to identify new targets for GC therapy. GC cells overexpressing Linc-ROR and GSAGS cells were cocultured with NK-92 cells, respectively, and Linc-ROR expression was determined using reverse transcription polymerase chain reaction. Linc-ROR overexpression experiments were used to measure the expression of MICB, a tumor protein that is recognized by natural killer (NK) cells. Bioinformatics analysis identified retinoid X receptor α (RXRA) and YY1 as MICB-specific transcription factors. Cotransfection and ubiquitinated drug experiments found that Linc-ROR promoted the ubiquitination and degradation of RXRA. Linc-ROR was upregulated in GC tissue and high expression was associated with tumor escape from NK-92 cell-mediated immunity. Linc-ROR overexpression inhibited the expression of MICB on the cell surface by degrading RXRA. These findings indicate that Linc-ROR promotes the binding of RXRA and E3 ligase UBE4B, reducing RXRA and MICB expression, and limiting NK cell-killing activity. Linc-ROR is a critical long noncoding RNA with a tumor-promoting function in GC and thus may serve as a potential therapeutic target.

Influence of tumor mycobiome on cancer pathogenesis (Review).

Cancer tissues harbor a large microbiome. There is growing evidence that the tumor microbiome is significantly correlated with the prognosis of cancer patients, but the exact underlying mechanisms have remained elusive. Although the tumor mycobiome is less abundant than the biome of bacteria, it is prevalent in most cancers in humans. The present review describes in detail the impact of the tumor mycobiome on cancer pathogenesis. The tumor mycobiome promotes tumor progression and metastasis by affecting the human immune system, maintaining a pro-inflammatory environment, producing aflatoxins, attenuating cell adhesion mechanisms and fungal-bacterial interactions. Furthermore, the tumor mycobiome likewise has great potential for cancer prevention, diagnosis and treatment.

Immune Response in H. pylori-Associated Gastritis and Gastric Cancer.

Helicobacter pylori (H. pylori) is the dominant member of the gastric microbiota and has infected more than half of the human population, of whom 5-15% develop gastric diseases ranging from gastritis and metaplasia to gastric cancer. These diseases always follow inflammation induced by cell surface and intracellular receptors and subsequent signaling, such as the NF-κB pathway and inflammasomes. Some types of immune cells are recruited to enforce an antibacterial response, which could be impeded by H. pylori virulence factors with or without a specific immune cell. Following decreased inflammation, neoplasm may appear with a little immune surveillance and may inhibit antitumor immunity. Therefore, the balance between H. pylori-associated inflammation and anti-inflammation is crucial for human health and remains to be determined. Here, we discuss multiple inflammation and immunoregulatory cells in gastritis and summarize the main immune evasion strategies employed by gastric cancer.