Tumor development is initiated by an accumulation of numerous genetic and epigenetic alterations that promote tumor initiation, invasion and metastasis. Astrocyte elevated gene-1 [AEG-1; also known as Metadherin (MTDH) and Lysine-rich CEACAM1 co-isolated (LYRIC)] has emerged in recent years as a potentially crucial mediator of tumor malignancy, and a key converging point of a complex network of oncogenic signaling pathways. AEG-1/MTDH has a multifunctional role in tumor development that has been found to be involved in the following signaling cascades: i) The Ha-Ras and PI3K/Akt pathways; ii) the nuclear factor-κB signaling pathway; iii) the ERK/mitogen-activated protein kinase and Wnt/β-catenin pathways; and iv) the Aurora-A kinase signaling pathway. Studies have established that AEG-1/MTDH is crucial in tumor progression, including transformation, the evasion of apoptosis, invasion, angiogenesis and metastasis. In addition, recent clinical studies have convincingly associated AEG-1/MTDH with tumor progression and poor prognosis in a number of cancer types, including hepatocellular, esophageal squamous cell, gallbladder and renal cell carcinomas, breast, non-small cell lung, prostate, gastric and colorectal cancers, and glioma, melanoma, neuroblastoma and osteosarcoma. AEG-1/MTDH may be used as a biomarker to identify subgroups of patients who require more intensive treatments and who are likely to benefit from AEG-1/MTDH-targeted therapies. The therapeutic targeting of AEG-1/MTDH may simultaneously block metastasis, suppress tumor growth and enhance the efficacy of chemotherapeutic treatments.

At present, it is commonly believed that tRFs and tiRNAs are formed by the specific and selective shear of tRNAs under certain pressure stimulation, rather than by random degradation of tRNA. tRFs and tiRNAs have been reported to contribute to the biological process of a variety of human cancers. However, the evidence for the mechanisms of tRFs and tiRNAs in the occurrence and development of gastric cancer (GC) is still insufficient. Here, we aimed to explore the carcinogenic roles of tRFs and tiRNAs in GC with RNA-sequencing technique, and found a novel 3’tRNA-derived fragment tRF-Val was significantly upregulated in GC tissues and cell lines. tRF-Val expression was positively correlated with tumor size and the depth of tumor invasion in GC tissues. Functionally, tRF-Val promoted proliferation and invasion, and inhibited apoptosis in GC cells. Mechanistically, tRF-Val directly bound to the chaperone molecule EEF1A1, mediated its transport into the nucleus and promoted its interaction with MDM2 (a specific p53 E3 ubiquitin ligase), thus inhibiting the downstream molecular pathway of p53 and promoting GC progression. These findings provided a new potential therapeutic target for GC and a new explanation for the occurrence of GC.

Novel targeted therapies need to be developed for gastric cancer, the third most common cancer type and the second most common cause of cancer-related mortality in China. Previous studies indicate that angiopoietin (Ang)-2 serves a role in the proliferation, migration, invasion and adhesion of malignant cells. The present study identified, using functional studies, that exogenous expression of miR-218 increased migration of NCI-87 and HGC-27 gastric cancer cells, which coincided with a reduction in the expression of Ang-2. In addition, intratumoral delivery of miR-218 inhibited proliferation and angiogenesis of gastric cancer cells in vivo, with a corresponding decreased in Ang-2 expression. These results indicate that miR-218 serves an important role in gastric cancer tumorigenesis through regulating the expression of Ang-2. Therefore, components of miR-218/Ang-2 signaling could provide novel therapeutic targets for the treatment of gastric cancer.

Background: miR-26b-5p is reported to be involved in the progression of multiple cancers, but its function and mechanism in human papillary thyroid cancer (PTC) remain unknown. We aimed to uncover the function and mechanism of miR-26b-5p in PTC. Methods: We performed qRT-PCR to detect the differences in miR-26b-5p expression between normal tissue and PTC. In vitro, we established cell lines stably overexpressing miR-26b-5p and investigated the function and underlying mechanism of miR-26b-5p in PTC. Results: miR-26b-5p was downregulated in PTC compared with normal tissue. miR-26b-5p was correlated with the clinical stage. miR-26b-5p inhibited the proliferation, invasion and migration of PTC cell lines. We next detected EMT and proliferation markers. miR-26b-5p was shown to exert its function in a β-catenin-dependent manner. Conclusion: Taken together, our results showed that miR-26b-5p inhibits proliferation, migration, invasion and EMT by degrading β-catenin.

Purpose This study aimed to investigate the characteristics of colonic neuroendocrine neoplasms (NENs) and to validate the prognostic value of the European Neuroendocrine Tumor Society (ENETS) and American Joint Committee on Cancer (AJCC) 8th staging systems. Methods A total of 167 and 1248 patients with colonic NENs from 12 medical centers across China and from the Surveillance, Epidemiology, and End Results (SEER) cancer registry in the United States, respectively, were reviewed. Patients were staged according to the ENETS and AJCC 8th staging systems. Results Clinicopathological features of colonic NENs in the Chinese cohort and SEER cohort were significantly distinct. In both the Chinese cohort and the SEER cohort, colonic neuroendocrine carcinoma (NEC) and mixed adeno‐neuroendocrine carcinoma (MANEC) were more frequent in the midgut than in the hindgut. Tumors originating from the midgut tended to be larger and at a more advanced stage than those from the hindgut. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC. Conclusions Our study revealed that tumors originating from the midgut and the hindgut shared different clinicopathological features. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC.

The incidence of gastric cancer is high, especially in China. The present study aims to provide a novel therapeutic target for gastric cancer. Peripheral blood, cancerous and paracancerous tissues were collected from patients with gastric cancer. T-cell immunoglobulin mucin domain-3 (Tim-3) expression in T-cells was measured and the correlation between Tim-3 expression and the T staging of gastric cancer was analyzed. The levels of T-cell secreted interferon (IFN)-γ and tumor necrosis factor (TNF)-α were assessed following Tim-3 signaling pathway activation. A nude mouse model of gastric cancer was established and Tim-3-stimulated T-cells were injected into the mice to evaluate tumor growth. The results of the present study demonstrated that Tim-3 expression levels from the paracancerous and cancerous gastric tissues were significantly increased compared with the peripheral blood, while its expression was significantly increased in cancerous compared with paracancerous gastric tissues. With the T staging of gastric cancer increasing, the expression of Tim-3 gradually increased. The activation of the Tim-3 signaling pathway in T-cells may inhibit IFN-γ and TNF-α secretion, and the results from the nude mice tumor model demonstrated that the inhibitory effect on tumor growth by T-cells was reduced by Tim-3 signaling pathway activation. The expression level of Tim-3 on the surface of tumor infiltrating T-cells in gastric cancer tissue increases significantly and the increased Tim-3 signaling may inhibit the function of T-cells. The results suggest that the increased expression of Tim-3 on T-cells may be involved the development of gastric cancer.

Gastric cancer (GC) is a high-incidence cancer worldwide. Most patients are diagnosed at an advanced stage, by which time they have limited treatment options and poor prognosis. Early diagnosis and precise treatment are important. In the past few years, emerging research has been conducted on the use of non-invasive liquid biopsy, with its advantages of minimal invasiveness and repeated sampling, to monitor tumor occurrence and recurrence in real time and to evaluate prognosis and treatment response. Many studies have demonstrated the potential of liquid biopsy in GC, and the detection of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), and exosomes has achieved gratifying results. In this review, we summarize evolving technologies for and information regarding liquid biopsy, the most recently discovered GC liquid biopsy biomarkers, and ongoing clinical trials and discuss the challenges and application prospects of liquid biopsy in GC.

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