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It was found in this study that long intergenic non-protein coding RNA 346 (LINC00346) was an lncRNA aberrantly expressed in gastric cancer (GC) based on multiple Gene Expression Omnibus (GEO) databases of GC cohorts. The LINC00346 gene was recurrently amplified and upregulated in GC, and its expression was positively correlated with poor pathologic stage, large tumor size, and poor prognosis. In addition, the oncogenic transcription factors KLF5 and MYC could bind to the LINC00346 promoter and enhance its expression. Gene Set Enrichment Analysis (GSEA) in the GEO datasets revealed that cell cycle and focal adhesion genes were enriched in patients with high LINC00346 expression. In vitro and in vivo assays of LINC00346 alterations revealed a complex integrated phenotype affecting cell growth, migration and invasion. Strikingly, high-throughput sequencing analysis after LINC00346 alterations highlighted alterations in cell cycle and focal adhesion pathways in GC cells. Mechanistically, argonaute 2 (Ago2) was recruited by LINC00346, which functioned as a molecular sponge for miR-34a-5p by antagonizing its ability to repress CD44, NOTCH1, and AXL protein translation. Taken together, our findings support a model in which the KLF5, MYC/LINC00346/miR-34a-5p cross-talk served as critical effectors in GC tumorigenesis and progression, suggesting a new therapeutic direction in the treatment of GC.

Accumulating data indicate that long noncoding RNAs (lncRNAs) serve as important modulators in biological processes and are dysregulated in diverse tumors. The function of FOXD2-AS1 in gastric cancer (GC) progression and related biological mechanisms remain undefined. A comprehensive analysis identified that FOXD2-AS1 enrichment was upregulated markedly in GC and positively correlated with a large tumor size, a later pathologic stage, and a poor prognosis. Gene-set enrichment analysis (GSEA) in GEO datasets uncovered that cell cycle and DNA replication associated genes were enriched in patients with high FOXD2-AS1 expression. Loss of FOXD2-AS1 function inhibited cell growth via inhibiting the cell cycle in GC, whereas upregulation of FOXD2-AS1 expression promoted cancer progression. The enhancer of zeste homolog 2 (EZH2) and lysine (K)-specific demethylase 1A (LSD1) proteins were found to serve as binding partners of FOXD2-AS1 and mediators of FOXD2-AS1 function. Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis.

Gastric cancer is the fourth most common type of cancer. Liver-intestine cadherin (CDH17) has been found to be involved in the proliferation and apoptosis of gastric cancer cells. Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumor and hematological malignancies. However, the mechanism of enhancing cisplatin-inducing effects on human gastric cancer BGC823 cells by blocking CDH17 gene, both in vitro and in vivo, remains to be clarified. In this study, we investigated the signaling pathway by which cisplatin induces apoptosis by blocking CDH17 gene in gastric cancer BGC823 cells. Our results indicate that down-expression of CDH17 gene can enhance apoptosis-inducing effects of cisplatin on human gastric cancer BGC823 cells. The expression levels of Bax and Cyt-c proteins were upregulated, but the expression levels of Bcl-2 and Bcl-xL proteins were downregulated by blocking CDH17 gene in gastric cancer BGC823 cells after treatment with cisplatin. Moreover, down-expression of CDH17 enhanced the efficacy of cisplatin-induced inhibition of tumor growth in nude mice via apoptosis induction. Down-expression of CDH17 gene can significantly improve apoptosis-inducing effects of cisplatin in vitro and in vivo, which is a new strategy to improve chemotherapeutic effects on gastric cancer.

Aim: To investigate the antinociceptive effect of adenosine agonist R-phenylisopropyl-adenosine (R-PIA) given to conscious rats by intracerebroventricular (ICV) and intrathecal (IT), and identify the effect of R-PIA on minimum alveolar concentration (MAC) of halothane with pretreatment of A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or K+ channel blocker 4-aminopyridine (4-AP)., Methods: Sprague-Dawley rats were implanted with 24-gauge stainless steel guide cannula using stereotaxic apparatus and ICV method, and an IT catheter (PE-10, 8.5 cm) was inserted into the lumbar subarachnoid space, while the rats were under pentobarbital anesthesia. After one week of recovery from surgery, rats were randomly assigned to one of the following protocols: MAC of halothane, or tail-flick latency. All measurements were performed after R-PIA (0.8-2.0 microg) microinjection into ICV and IT with or without pretreatment of DPCPX or 4-AP., Results: Microinjection of adenosine agonist R-PIA in doses of 0.8-2.0 microg into ICV and IT produced a significant dose- and time-dependent antinociceptive action as reflected by increasing latency times and ICV administration of adenosine agonist R-PIA (0.8 microg) reducing halothane anesthetic requirements (by 29%). The antinociception and reducing halothane requirements effected by adenosine agonist R-PIA was abolished by DPCPX and 4-AP., Conclusion: ICV and IT administration of adenosine agonist R-PIA produced an antinociceptive effect in a dose-dependent manner and decreased halothane MAC with painful stimulation through activation of A1 receptor subtype, and the underlying mechanism involves K+ channel activation.