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Aims The oncogenic role of lncRNA Hotair has been acknowledged in subset of malignancies, including gastric cancer (GC). However, the detailed molecular mechanisms that contribute to its oncogenic role of are largely elusive. This study was designed to explore the underlying mechanism that contributes the regulatory role of Hotair in GC pathogenesis and progression. Main methods Expression pattern of lncRNAs in GC tissues and adjacent normal tissues were identified by using microarray analysis. The cell proliferation of GC cells was examined by CCK-8 assay and colony formation assay, while migration and invasion capabilities of GC cells were examined by Transwell (with or without Matrigel) assay. Cell apoptosis was examined by Flow cytometer. qRT-PCR and western blotting were used to examine the expression of Hotair, miR-217, and other related genes. The potential target relationships were predicted by miRcode algorithm, and validated by dual luciferase reporter gene assay. Key findings We observed that Hotair was frequently up-regulated in GC tissues and cell lines, and high Hotair level was positively correlated with poor prognosis in GC patients. Knockdown of Hotair inhibited GC cells' viability, migration, invasion, Epithelial mesenchymal transition process. MiR-217 was decreased while GCP5 was increased in GC cells. Hotair negatively regulated the expression of miR-217 in GC while miR-217 targeted GCP5 to down-regulate its expression. Hotair promoted GC development by promoting GCP5 expression via sponging miR-217. Significance Hotair could serve as a potentially prognostic indicator and provide new light into its underlying biological-molecular mechanism in GC.

Drug resistance is a big obstacle for clinical anti-tumor treatment outcome. However, the role of HOTAIR in drug resistance in gastric cancer (GC) remains unknown. In this study, we showed that overexpression of HOTAIR enhanced paclitaxel and doxorubicin resistance in GC cells. Furthermore, the expression of HOTAIR was upregulated in GC tissues and higher expression of HOTAIR was associated with late stage. In addition, we showed that miR-217 expression was lower in GC tissues compared with the paired non-tumour tissues and downregulated expression of miR-217 was correlated with late stage. Interestingly, the expression of miR-217 was negatively correlated with HOTAIR expression in GC tissues. Ectopic expression of HOTAIR increased GC cell proliferation, cell cycle, and migration. Elevated expression of HOTAIR suppressed miR-217 expression and enhanced GPC5 and PTPN14 expression. Furthermore, we demonstrated that overexpression of miR-217 suppressed paclitaxel and doxorubicin resistance in GC cells. Ectopic expression of HOTAIR promoted drug resistance and increased GC cell proliferation, cell cycle, and migration by targeting miR-217. These data suggested that overexpression of HOTAIR enhanced paclitaxel and doxorubicin resistance in GC cells through inhibiting miR-217 expression.

Background/objective Gastric cancer (GC) is the second leading cause of death resulted from cancer globally. The most common cause of GC is the infection of Helicobacter pylori, approximately 11% of cases are caused by genetic factors. The objective of this study was to develop an effective computational method to meaningfully interpret these GC-related genes and to predict potential prognostic genes for clinical detection. Methods We employed the shortest path algorithm and permutation test to probe the genes that have relationship with known GC genes in gene–gene interaction network. We calculated the enrichment scores of gene ontology and pathways of gastric cancer related genes to characterize these genes in terms of molecular features. The optimal features that primly representing the gastric cancer related genes were selected using Random Forest classification and incremental feature selection. Random Forest classification was also used for the prediction of the novel gastric cancer related genes based on the selected features and the identification of novel prognostic genes based on the expression of genes. Results Based on the shortest path analysis of 36 known GC genes, 39 genes occurring in shortest path were identified as GC-related genes. In subsequent classification, 4153 gene ontology terms and 157 pathway terms were identified as the optimal features to depict these gastric cancer related genes. Based on them, a total of 886 genes were predicted as related genes. These 886 genes could serve as expression biomarkers for clinical detection and they achieved a 100% accuracy for distinguishing gastric cancer from a case-control dataset, better than any of 886 random selected genes did. Conclusion By analyzing the features of known GC-related genes, we employed a systematic method to predict gastric cancer related genes and novel prognostic genes for accurate clinical detection.

Increasing evidences demonstrated that microRNAs (miRNAs) play critical roles in the human tumor development and progression. In our study, we found that miR-330-3p expression was downregulated in gastric cancer cell lines and tissues. Ectopic expression of miR-330-3p suppressed the gastric cancer cell proliferation, colony formation and migration. Overexpression of miR-330-3p promoted E-cadherin expression and inhibited the expression of N-cadherin, vimentin and snail. We identified Musashi-1 (MSI1) as a direct target gene of miR-330-3p in gastric cancer cell. In addition, MSI1 was upregulated in gastric cancer cell lines and tissues and the MSI1 expression was inversely correlated with miR-330-3p expression in gastric cancer tissues. MiR-330-3p expression was increased in gastric cancer cells after treated with histone deacetylase inhibitor trichostatin A (TSA) and DNA methylation inhibitor 5-aza-CdR (AZA). These indicated that downregulated expression of miR-330-3p was partly mediated by gene promoter region hypermethylation. These results suggested that miR-330-3p acted as a tumor suppressor gene in GC.