Non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have been identified as crucial regulators of various biological processes through epigenetic regulation, transcriptional regulation, and post-transcriptional regulation. Growing evidence suggests that dysregulation and activation of non-coding RNAs are closely associated with tumor angiogenesis, a process essential for tumor growth and metastasis and a major contributor to cancer-related mortality. Therefore, understanding the molecular mechanisms underlying tumor angiogenesis is of utmost importance. Numerous studies have documented the involvement of different types of non-coding RNAs in the regulation of angiogenesis. This review provides an overview of how non-coding RNAs regulate tumor angiogenesis. Additionally, we discuss emerging strategies that exploit non-coding RNAs for anti-angiogenic therapy in cancer treatment. Ultimately, this review underscores the crucial role played by non-coding RNAs in tumor angiogenesis and highlights their potential as therapeutic targets for anti-angiogenic interventions against cancer.

Introduction: CD155 is recently emerging as a promising target in malignancies. However, the relationship between CD155 expression and tumor microenvironment (TME) cell infiltration in gastric adenocarcinoma (GAC) has rarely been clarified.Methods: We measured CD155 expression in specimens of gastric precancerous disease and GAC by immunohistochemistry. The association of CD155 expression with GAC progression and cells infiltration in TME was evaluated through 268 GAC tissues and public dataset analysis.Results: We showed that the expression of CD155 was positively correlated with the pathological development of gastric precancerous disease (r = 0.521, P < 0.0001). GAC patients with high CD155 expression had a poorer overall survival (P = 0.033). Moreover, CD155 expression correlated with aggressive clinicopathological features including tumor volume, tumor stage, lymph node involvement, and cell proliferation (P &lt;0.05). Remarkably, CD155 expression positively related to the infiltration of CD68+ macrophages in TME (P = 0.011). Meanwhile, the positive correlation was observed between CD155 and CD31 (P = 0.026). In addition, patients with high CD155 expression combined with low CD3, CD4, CD8, IL-17, IFN-γ or CD19 expression as well as those with high CD155 and α-SMA expression showed significantly worse overall survival (P < 0.05).Conclusions: CD155 may play a pivotal role in the development of GAC through both immunological and non-immunological mechanisms and be expected to become a novel target of immunotherapy in GAC patients.

Programmed death-ligand 1 (PD-L1) is a crucial negative costimulatory molecule expressed on both tumor and immune cells. It binds to programmed death-1, facilitating tumor escape. Tumor-infiltrating immune cells play a vital role in this process. However, the clinical relationship between PD-L1 expression and tumor-infiltrating immune cells remains uncertain. Immunohistochemistry (IHC) was utilized to assess PD-L1 expression and TIIC markers (CD3, CD4, CD8, CD19, CD31, CD68, CD11c, CD56, and α-smooth muscle actin) in gastric adenocarcinoma tissues from 268 patients. The aim was to explore the prognostic significance of PD-L1 and the infiltration of different immune cell types. The study analyzed overall survival and the correlations between PD-L1 expression, immune cell infiltration, and clinicopathological characteristics. Among the 268 patients, 52 (19.40%) exhibited high PD-L1 expression on tumor cells (TPD-L1), while 167 (62.31%) displayed high PD-L1 expression on immune cells (IPD-L1). Patients with high IPD-L1 expression showed improved survival compared to those with low IPD-L1 expression (P = .028). High TPD-L1 expression associated with various clinicopathological features, such as larger tumor size, poorer differentiation, deeper invasion depth, and higher tumor stage. Conversely, patients with high IPD-L1 expression exhibited shallower tumor invasion and lower mortality rates. Univariate analysis indicated that superficial tumor infiltration, absence of lymph node and distant metastasis, low tumor stage, high IPD-L1 expression, and elevated CD8 and CD19 expression were associated with a reduced risk of tumor progression. Multivariate analysis revealed that patients with high IPD-L1 and CD8 expression or high TPD-L1 and low CD31 expression experienced significantly better overall survival than patients with other combinations. The findings indicate that patients with high PD-L1 expression in immune cells have a substantially improved prognosis. Additionally, the combination of PD-L1 with CD8 or CD31 expression status can serve as an indicator of prognosis in patients with gastric adenocarcinoma.

B7H3 (B7 homolog 3) is an important immune checkpoint molecule in the B7-CD28 family, and substantial evidence indicates that it promotes tumor growth, invasion, and metastasis. The imbalance between oxygen supply and consumption in the tumor microenvironment induces hypoxia, which activates hypoxia-inducible factor-1α (HIF-1α) signaling. HIF-1α plays a critical role in tumor growth, metastasis, and immune evasion. However, the interaction between HIF-1α and B7H3 in gastric cancer remains unclear. In this study, we explored the expression characteristics and correlation of B7H3 and HIF-1α in large gastric cancer samples using bioinformatics and immunohistochemical methods. The results show that B7H3 and HIF-1α mRNA are significantly upregulated in gastric cancer, with a strong positive correlation between their expressions. In gastric cancer tissues, no significant correlation was found between B7H3 and HIF-1α expression (r _S = 0.070, P = 0.257), whereas high B7H3 expression demonstrated a moderate positive correlation with nuclear expression of HIF-1α (r _S = 0.141, P = 0.021). Furthermore, we found that nuclear expression of HIF-1α was closely associated with poor prognosis in gastric cancer patients ( P < 0.001) and could serve as an independent risk factor. Notably, knockdown of B7H3 in gastric cancer cells significantly inhibited both the expression and nuclear localization of HIF-1α, whereas overexpression of B7H3 markedly promoted HIF-1α expression. In conclusion, the combination of B7H3 and HIF-1α may serve as a novel prognostic biomarker for gastric cancer and also holds potential as a therapeutic target for its treatment.