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Decreased expression of the long non-coding RNA HOXD-AS2 promotes gastric cancer progression by targeting HOXD8 and activating PI3K/Akt signaling pathway 被引量:4
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作者 Lin Yao Peng-Cheng Ye +7 位作者 Wang Tan Ya-Jun Luo Wan-Ping Xiang Zi-Lin Liu Zhi-Ming Fu Fei Lu Ling-Han Tang Jiang-Wei Xiao 《World Journal of Gastrointestinal Oncology》 SCIE CAS 2020年第11期1237-1254,共18页
BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucida... BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucidated.AIM To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC.METHODS Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pc HOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXDAS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.RESULTS The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.CONCLUSION These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC. 展开更多
关键词 Long non-coding RNA Gastric cancer hoxd-as2 HOXD8 PI3K/AKT PROGRESSION
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长非编码RNA HOXD⁃As2通路抑制直肠癌细胞增殖、转移作用机制研究
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作者 叶鹏程 杨钧淞 +3 位作者 唐锦 谭淼 吴东津 魏寿江 《临床军医杂志》 CAS 2023年第7期699-703,共5页
目的探讨长非编码RNA(LncRNA)HOXD⁃As2通路抑制直肠癌细胞增殖、转移的潜在机制。方法在直肠癌HCT116与HT29细胞中,转染阴性设为对照组,转染LncRNA HOXD⁃As2过表达质粒设为HOXD⁃As2组;转染空载体Vector设为Vector组,转染HOXD8过表达质... 目的探讨长非编码RNA(LncRNA)HOXD⁃As2通路抑制直肠癌细胞增殖、转移的潜在机制。方法在直肠癌HCT116与HT29细胞中,转染阴性设为对照组,转染LncRNA HOXD⁃As2过表达质粒设为HOXD⁃As2组;转染空载体Vector设为Vector组,转染HOXD8过表达质粒设为HOXD8组。采用荧光素酶报告实验检测LncRNA HOXD⁃As2与靶基因HOXD8的相互作用。检测并比较4组细胞活力、增殖、侵袭、细胞迁移水平、上皮⁃间质转化相关蛋白表达水平及磷酸化蛋白激酶B/蛋白激酶B(p⁃AKT/AKT)、磷酸化磷脂酰肌醇⁃3⁃激酶/磷脂酰肌醇⁃3⁃激酶(p⁃PI3K/PI3K)、磷酸化雷帕霉素机械靶蛋白/雷帕霉素机械靶蛋白(p⁃mTOR/mTOR)蛋白相对表达水平。结果与对照组相比,HOXD⁃As2组荧光素酶活性下降,而mRNA、蛋白相对表达情况增加,差异均有统计学意义(P<0.05)。与对照组相比,HOXD⁃As2组直肠癌细胞HCT116、HT29中HOXD8的mRNA与蛋白表达水平均显著上升,差异均有统计学意义(P<0.05)。与Vector组相比,HOXD8组直肠癌细胞HCT116、HT29细胞活力、细胞增殖、细胞侵袭、细胞迁移水平及神经性钙粘蛋白、基质金属蛋白酶9蛋白表达均显著下降,上皮性钙粘蛋白表达增加,差异均有统计学意义(P<0.05)。HOXD⁃As2组直肠癌细胞HCT116、HT29中p⁃AKT/AKT、p⁃PI3K/PI3K、p⁃mTOR/mTOR水平均低于对照组,差异均有统计学意义(P<0.05)。HOXD8组直肠癌细胞HCT116、HT29中p⁃AKT/AKT、p⁃PI3K/PI3K、p⁃mTOR/mTOR水平均低于Vector组,差异均有统计学意义(P<0.05)。结论LncRNA HOXD⁃As2通过与靶基因HOXD8相互作用,上调HOXD8的mRNA、蛋白表达水平,抑制PI3K/Akt通路,降低直肠癌细胞增殖与转移水平。 展开更多
关键词 长非编码RNA HOXD⁃As2 上皮性钙粘蛋白 神经性钙粘蛋白 基质金属蛋白酶9 磷脂酰肌醇⁃3⁃激酶 蛋白激酶B 直肠癌
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