目的：探讨lncRNA-Z38对胃癌细胞恶性生物学行为的影响及其可能的调控机制。方法：构建lncRNA-Z38稳定过表达的胃癌细胞系（AGS、MKN74 细胞），通过细胞成球实验检测过表达 lncRNA-Z38 对胃癌细胞肿瘤特征的影响。对过表达lncRNA-Z38的AGS细胞及对照细胞进行高通量测序，对差异表达基因进行KEGG富集分析，筛选出可能参与调控胃癌发生发展的信号通路，采用WB等技术验证lncRNA-Z38通过调控该信号通路参与提高胃癌细胞的干性。结果：成功构建lncRNA-Z38过表达细胞株，细胞成球实验提示lncRNA-Z38过表达细胞的成球能力显著高于对照细胞（P<0.05）。通过测序筛选出 lncRNA[1]Z38 过表达胃癌细胞中的 1 999 个差异表达基因，其中上调基因1 238个、下调基因761个 ；经 KEGG 富集分析得到其中变化最显著的通路为TGF-β信号通路（P<0.05）。WB实验结果提示，lncRNA-Z38高表达胃癌细胞中TGF-β信号通路组成基因编码蛋白ID3、BMP6显著上调（均P<0.05）、GDF-5、WNT8B显著下调（P<0.05）。结论：在胃癌中高度表达的lncRNA-Z38通过调控TGF-β信号通路提高胃癌细胞的干性。

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.

山东省医药卫生科技发展计划项目（No. 2018WS076）；医学免疫学国家重点实验室开放课题（No. NKMI2018K11）；潍坊市科学技 术发展计划项目（No. 201302030）