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Basic Research
lncRNA-Z38 promotes occurrence and progression of gastric cancer though regulating TGF-β signaling pathway
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Abstract:
Objective: To explore the effect of lncRNA-Z38 on malignant biological behavior of gastric cancer cells, and the possible regulatory mechanism. Methods: Gastric cancer cell lines (AGS,MKN74 cells) stably over-expressing lncRNA-Z38 were constructed，and the effect of lncRNA-Z38 over-expression on the stemness of gastric cancer cells was detected through sphere forming assay. High-throughput sequencing of AGS cells with lncRNA-Z38 over-expression and the control cells was performed, and KEGG enrichment analysis was done on the differentially expressed genes to find the potential signaling pathway involved in regulating the occurrence and development of gastric cancer. Furthermore, WB was conducted to verify that lncRNA-Z38 regulates the signaling pathway to promote the stemness of gastric cancer cells. Results: Cell lines with stable lncRNA-Z38 over-expression were successfully constructed. Sphere forming assay suggested that the sphere-forming ability of lncRNA-Z38 overexpressed gastric cancer cells was significantly higher than their control cells (P<0.05). According to the high-throughput sequencing results, 1 999 differentially expressed genes in lncRNA-Z38 over-expressed gastric cancers cells were screened out, among which 1 238 were up-regulated and 761 were downregulated. KEGG pathway enrichment analysis showed that the most significantly enriched pathway was TGF-β signaling pathway (P<0.05). Further, WB results verified that the encoding proteins of TGF-β pathway constituent genes ID3 and BMP6 were significantly up-regulated while GDF-5 and WNT8B were significantly down-regulated in lncRNA-Z38 over-expressed gastric cancer cells (P<0.05). Conclusion: Highly expressed lncRNA-Z38 enhances the stemness of gastric cancer cells through regulating the TGF-β pathway.
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Project Supported:
Project supported by the Medical Health Science and Technology Development Program of Shandong Province (No. 2018WS076), the Open Project of the National Key Laboratory of Medical Immunology (No. NKMI2018K11), and the Science and Technology Development Project of Weifang City (No. 201302030)
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