目的探讨超级增强子(super enhancers,SE)-HOXC13-AS对胰腺癌生物学行为的影响及临床意义。方法采用qRT-PCR法检测HOXC13-AS在胰腺癌组织和细胞中的表达,分析HOXC13-AS表达与胰腺癌临床病理特征的关系。选择siRNA转染HOXC13-AS表达量最...目的探讨超级增强子(super enhancers,SE)-HOXC13-AS对胰腺癌生物学行为的影响及临床意义。方法采用qRT-PCR法检测HOXC13-AS在胰腺癌组织和细胞中的表达,分析HOXC13-AS表达与胰腺癌临床病理特征的关系。选择siRNA转染HOXC13-AS表达量最高的PANC-1细胞,应用CCK-8法、细胞周期实验、划痕实验、Transwell实验及细胞凋亡实验检测敲低HOXC13-AS对胰腺癌细胞增殖、迁移、侵袭及凋亡的影响。应用生物数据库分析和JQ1抑制剂验证SE与HOXC13-AS之间调控关系,并通过CCK-8法、划痕实验、Transwell实验及细胞凋亡实验检测抑制SE-HOXC13-AS对胰腺癌细胞增殖、迁移、侵袭及凋亡的影响。结果胰腺癌组织中HOXC13-AS平均表达量(4.40±6.21)显著高于癌旁组织(1.01±0.02,P<0.05),HOXC13-AS表达与胰腺癌分化程度和临床分期密切相关。与正常胰腺导管上皮细胞(0.93±0.11)相比,胰腺癌细胞株BXPC-3(2.55±0.19)、SW1990(5.49±0.92)、CF-PAC1(12.27±0.60)及PANC-1(70.39±6.40)中HOXC13-AS的表达升高(P<0.05)。敲低PANC-1细胞中HOXC13-AS表达可明显抑制胰腺癌细胞增殖、迁移和侵袭能力,促进细胞凋亡。抑制PANC-1细胞中SE可显著下调HOXC13-AS的表达(0.65±0.02 vs 0.41±0.02,P<0.05),并可能进一步抑制胰腺癌细胞增殖、迁移和侵袭能力,促进细胞凋亡。结论HOXC13-AS在胰腺癌中高表达,敲低HOXC13-AS可抑制胰腺癌的进展。SE调控HOXC13-AS的表达,并可能进一步影响胰腺癌的生物学行为。展开更多
Hoxc13 has an important role in controlling hair formation. In this study, we examine the Hoxc13 RNA expression pattern of skin during embryo development. The result indicated that changes of the Hoxe13 gene expressio...Hoxc13 has an important role in controlling hair formation. In this study, we examine the Hoxc13 RNA expression pattern of skin during embryo development. The result indicated that changes of the Hoxe13 gene expression and thickness of skin have a similar trend during hair follicle morphogenesis. In interpreting these results, we investigated whether the regulation motifs is in Hoxc13 intron, which is a 5.4 kb fragment. To blast with other mammals, we found a very conservative region in all mammal animals and two regions in livestock, such as cow, sheep, horse, dog, and so on, which are not in other Hox genes. We have examined putative pre-miRNA in this region, providing an entry point for elucidating currently unknown mechanisms that are required for regulating quantitative levels of Hoxc13 gene expression.展开更多
文摘目的探讨超级增强子(super enhancers,SE)-HOXC13-AS对胰腺癌生物学行为的影响及临床意义。方法采用qRT-PCR法检测HOXC13-AS在胰腺癌组织和细胞中的表达,分析HOXC13-AS表达与胰腺癌临床病理特征的关系。选择siRNA转染HOXC13-AS表达量最高的PANC-1细胞,应用CCK-8法、细胞周期实验、划痕实验、Transwell实验及细胞凋亡实验检测敲低HOXC13-AS对胰腺癌细胞增殖、迁移、侵袭及凋亡的影响。应用生物数据库分析和JQ1抑制剂验证SE与HOXC13-AS之间调控关系,并通过CCK-8法、划痕实验、Transwell实验及细胞凋亡实验检测抑制SE-HOXC13-AS对胰腺癌细胞增殖、迁移、侵袭及凋亡的影响。结果胰腺癌组织中HOXC13-AS平均表达量(4.40±6.21)显著高于癌旁组织(1.01±0.02,P<0.05),HOXC13-AS表达与胰腺癌分化程度和临床分期密切相关。与正常胰腺导管上皮细胞(0.93±0.11)相比,胰腺癌细胞株BXPC-3(2.55±0.19)、SW1990(5.49±0.92)、CF-PAC1(12.27±0.60)及PANC-1(70.39±6.40)中HOXC13-AS的表达升高(P<0.05)。敲低PANC-1细胞中HOXC13-AS表达可明显抑制胰腺癌细胞增殖、迁移和侵袭能力,促进细胞凋亡。抑制PANC-1细胞中SE可显著下调HOXC13-AS的表达(0.65±0.02 vs 0.41±0.02,P<0.05),并可能进一步抑制胰腺癌细胞增殖、迁移和侵袭能力,促进细胞凋亡。结论HOXC13-AS在胰腺癌中高表达,敲低HOXC13-AS可抑制胰腺癌的进展。SE调控HOXC13-AS的表达,并可能进一步影响胰腺癌的生物学行为。
基金supported by the Ministry of Science and Technology of China (2007AA10Z151,2007BAD56B03,and 30660122)the Inner Mongolia Natural Science Foundation,China (2007NM2010)
文摘Hoxc13 has an important role in controlling hair formation. In this study, we examine the Hoxc13 RNA expression pattern of skin during embryo development. The result indicated that changes of the Hoxe13 gene expression and thickness of skin have a similar trend during hair follicle morphogenesis. In interpreting these results, we investigated whether the regulation motifs is in Hoxc13 intron, which is a 5.4 kb fragment. To blast with other mammals, we found a very conservative region in all mammal animals and two regions in livestock, such as cow, sheep, horse, dog, and so on, which are not in other Hox genes. We have examined putative pre-miRNA in this region, providing an entry point for elucidating currently unknown mechanisms that are required for regulating quantitative levels of Hoxc13 gene expression.
