The aim of the present study was to research the mechanism of action of microRNA-144 (miR-144) in colorectal cancer (CRC) and its role in tumor progression. It was demonstrated that miR-144 was downregulated and anoctamin 1 (ANO1) expression was upregulated in CRC. The expression of ANO1 was negatively associated with that of miR-144 in CRC. The present study indicated that upregulated expression of ANO1 was associated with poor differentiation and advanced tumor-node-metastasis stage. It was verified that upregulation of ANO1 expression activated the epidermal growth factor receptor/extracellular signal-regulated kinase signaling pathway. It was also demonstrated that miR-144 exerts strong tumor-inhibiting effects by targeting ANO1. Therefore, miR-144 may have potential as a prognostic marker or therapeutic target for CRC.

FOSB protein is encoded by the FOSB gene in humans, which shares structural similarities with the prototype of the Fos family. FOSB plays a role by AP-1 complex which is composed of heterodimers of Jun and Fos members. Our experiment aimed to evaluate the effect of FOSB in gastric cancer (GC) patients and then probe its significance in prognosis. We detected the expression of FOSB in GC and adjacent non-cancerous tissues by western blot analysis and real-time quantitative PCR (qRT-PCR). Moreover, we analyzed FOSB expression in patients who underwent resection procedures using immunohistochemistry. The relationship between the expression of FOSB, the clinicopathological characteristics and the patients survival were also investigated. Furthermore, in vitro, we evaluated the effects of FOSB gene on gastric cancer cell viability, proliferation and migration by MTT, clone formation and transwell assays. Finally, the Kaplan-Meier method and log-rank test were used to compare the overall survival between high FOSB expression group and low FOSB expression group. Immunohistochemical staining data showed that FOSB expression was significantly decreased in gastric cancer cases. In addition, we confirmed FOSB downregulation in both mRNA and protein levels in GC tissues compared with matched adjacent non-cancerous tissues. Downregulated expression of FOSB was correlated with poor differentiation, lymph node metastasis and advanced TNM stage. Moreover, we found that low FOSB expression exhibited a significant correlation with poor prognosis for GC patients by Kaplan-Meier survival analysis. Overexpression of FOSB significantly suppressed cell proliferation, clone formation and migration in GC cell lines. In contrast, silencing of FOSB expression in GC cells promoted proliferation, clone formation and migration. Our results showed that FOSB plays a crucial role in the suppression of GC, and that it may be a useful biomarker in diagnosis and prognosis for GC patients.

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Gastric cancer (GC) is one of the main causes of the high death rate in the world. But the molecular mechanisms of GC carcinogenesis remain little known. This study aimed to identify novel promising biomarkers of GC and reveal its potential molecular mechanisms by integrating bioinformatics analysis. We screened the overlapped differentially expressed genes (DEGs) of TCGA and several GEO datasets. Among these DEGs, we used protein-protein interactions network analysis to recognize the hub genes. Moreover, functional enrichment analysis including GO and KEGG pathway analysis and gene set enrichment analysis (GSEA) were performed to study the role of DEGs and potential underlying mechanisms of GC. Based on integrated bioinformatics analysis, SERPINH1, COL1A2, COL8A1, COL4A1, COL5A1, COL12A1, and COL1A1 were screened as candidate diagnostic marker genes. In addition, SERPINH1 was identified as a core gene in the regulation of GC development. Furthermore, we confirmed that SERPINH1 could promote the proliferation, migration, and cell cycle of GC cells. Our present study demonstrated that SERPINH1 was a core therapeutic biomarker in the regulation of candidate genes involved in GC progression.

| INTRODUC TI ONGastric cancer (GC) is one of the most common groups of malignancies in the world. There are one million new cases worldwide each year, mainly in developing countries, especially in China. The incidence of GC is second in various cancers in China. 1 As in recent decades in China for GC prevention and control efforts, the effect of treatment for GC has occurred great changes, but the survival rate remains poor. 2The specific mechanism of the occurrence and development of GC are still not entirely clear. In these years, many studies have confirmed that Abstract Nowadays, research on CSCs is still in an initial stage, and there are few studies reporting the successful isolation and identification of CSCs. In the present study, we attempted to isolate CSCs through cultivating the cell line MKN45 in defined serum-free medium and study the expression of stem cell markers or related proteins (Oct3/4, Sox2, Nanog and CD44) in CSCs. Moreover, immunofluorescence staining was performed to validate the stem cell markers of spheroid body-forming cells.Further experiments were used to evaluate the SPOP expression in tumorsphere cells. In addition, ADAMTS9-AS2 is a lncRNA that contributes to the genesis and development of many cancers, including gastric cancer (GC). We found ADAMTS9-AS2 functioned as an anti-oncogene and positively correlated with the expression of SPOP in GC tissues by combining bioinformatics analyses. Furthermore, we reported that ADAMTS9-AS2 regulated the expression of SPOP in GC cells and tumorsphere cells to inhibit GC progression. Together, our results demonstrated that SPOP and ADAMTS9-AS2 can be potential targets for GC treatment. K E Y W O R D S ADAMTS9-AS2, cancer stem cells, gastric cancer, Speckle-type POZ protein, tumorsphere S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Wang F, Tang C, Xu D, et al. LncRNA ADAMTS9-AS2 suppresses the proliferation of gastric cancer cells and the tumorigenicity of cancer stem cells through regulating SPOP.