Background: HOXA10 has been reported to be deregulated in many kinds of cancers including gastric cancer. But its role in gastric cancer progression is controversial. Therefore, the current study was performed to explore the role and mechanism of HOXA10 in gastric cancer. Materials and methods: IHC and Western blotting assays were used to assess HOXA10 expression in gastric cancer tissues and cells. Lentivirus infection was used to alter HOXA10, STAT3 and JAK1 expression in gastric cancer NCI-N87 and MKN28 cells. MTT, cloning formation, flow cytometry and in vivo xenotransplantation experiments were carried out to assess cell proliferation, cloning formation, apoptosis and tumorigenesis. Results: HOXA10 expression was obviously increased in gastric cancer tissues and cells when compared with the normal gastric tissue samples and cells. Upregulation of HOXA10 significantly enhanced cell proliferation, cloning formation and tumorigenesis abilities and reduced cell apoptosis in gastric cancer, and promoted the activation of JAK1/STAT3 signaling. In addition, we showed that the effects of HOXA10 on the promotion of cell viability and tumorigenesis and cell apoptosis repression were all weakened when JAK1 or STAT3 was downregulated. Conclusion: This study demonstrates that HOXA10 functions as an oncogene in gastric cancer through activating JAK1/STAT3 signaling.

Background: Gastric cancer is a highly aggressive malignant tumor with heterogeneity and is still a global health problem. The present study aimed to investigate the role of Cyclin I-like (CCNI2) in the regulation of phenotype and tumorigenesis, as well as its underlying mechanisms. Method: The expression profile of CCNI2 in gastric cancer was determined based on The Cancer Genome Atlas (TCGA) database and immunohistochemical staining. The effects of altered CCNI2 expression on the biological phenotypes such as proliferation, clone formation, apoptosis and migration of gastric cancer cell lines BGC-823 and SGC-7901 were investigated. Mice xenograft models were established to reveal the role of CCNI2 knockdown on tumorigenesis. The potential mechanism of CCNI2 regulating gastric cancer was preliminarily determined by RNA sequencing. Result: CCNI2 was abundantly expressed in gastric cancer and was positively correlated with pathological stage. Knockdown of CCNI2 slowed down the malignant progression of gastric cancer by inhibiting tumor cell proliferation, increasing the susceptibility to apoptosis and suppressing migration. Moreover, downregulation of CCNI2 attenuated the ability of gastric cancer cells to form tumors in mice. Additionally, there was an interaction between CCNI2 and transcription factor hepatoma-derived growth factor (HDGF) in SGC-7901 cells. Knockdown of CCNI2 alleviated the promoting effects of HDGF overexpression in gastric cancer cells. Conclusions: CCNI2 promoted the progression of human gastric cancer through HDGF, which drew further interest regarding its clinical application as a potential therapeutic target.

Background: Multi-organ metastasis has been the main cause of death in patients with Gastric cancer (GC). The prognosis for patients with metastasized GC is still very poor. Long noncoding RNAs (lncRNAs) always been reported to be closely related to cancer metastasis.Methods: In this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected by Transwell, Wound healing, Western Blot or other assays in vitro and in vivo. Further mechanism study was performed by RNA FISH, Dual-luciferase reporter assay and RT-qPCR. Finally, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 in patient tissues was detected by RT-qPCR.Results: In this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected in vitro and in vivo. The results shown that overexpression of the lncRNA CADM2-AS1 promoted GC metastasis, while knockdown inhibited it. Further mechanism study proved that lncRNA CADM2-AS1 could sponge and silence miR-5047, which targeting mRNA was NOTCH4. Elevated expression of lncRNA CADM2-AS1 facilitate GC metastasis by up-regulating NOTCH4 mRNA level consequently. What’s more, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 was further detected and verified in metastatic GC patient tissues.Conclusions: LncRNA CADM2-AS1 promoted metastasis in GC by targeting the miR-5047/NOTCH4 signaling axis, which may be a potential target for GC metastasis.