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低氧微环境下BANCR调控HIF-1α促进胰腺癌微淋巴管生成

BANCR regulates HIF-1αto promote microlymphangiogenesis in pancreatic cancer under hypoxic microenvironment
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摘要 目的研究低氧条件下BANCR对胰腺癌低氧诱导因子(HIF-1α)的调控作用及其对胰腺癌细胞微淋巴管生成的影响。方法qRT-PCR检测常氧及低氧条件下胰腺癌细胞(SW1990、PANC-1)中BANCR的表达。siRNA干扰胰腺癌细胞中BANCR的表达,并与人淋巴管内皮细胞(HDLEC)分别在常氧和低氧条件下进行3D共培养,并统计微淋巴管生成密度(MLVD)。应用qRT-PCR检测si-BANCR组和si-NC组胰腺癌细胞中HIF-1α蛋白及其mRNA的相对表达量。实验数据应用SPSS 19.0统计学软件进行统计分析。BANCR和HIF-1α的表达水平及MLVD以(x±s)表示,组间对比采用独立样本t检验;以P<0.05为差异有统计学意义。结果与常氧组(Normoxia)相比,低氧组(Hypoxia)的胰腺癌细胞中BANCR表达水平显著增高(P<0.01);干扰BANCR表达,与常氧组相比si-NC组和si-BANCR组在低氧条件下MLVD均明显增加(P<0.001),且沉默BANCR的表达,可显著降低PC细胞中MLVD水平(P<0.05);低氧条件下培养两种PC细胞株,与BANCR-siRNA组相比,NC组HIF-1α蛋白及其mRNA表达水平显著增高。结论低氧条件下胰腺癌细胞株(SW1990、PANC-1)中BANCR表达增加,可在转录和翻译水平上调HIF-1α表达,在胰腺癌微淋巴管生成和淋巴结转移中扮演重要角色。 Objective To study the regulation of BANCR on pancreatic cancer HIF-1αand its effect on microlymphangiogenesis in pancreatic cancer cell-lines under hypoxic conditions.Methods qRT-PCR was used to detect the expression of BANCR in pancreatic cancer cell-lines(SW1990,PANC-1)under normoxia and hypoxia respectively.The expression of BANCR of pancreatic cancer cell-lineswere interfered by siRNA,and were 3D co-cultured with human lymphatic endothelial cells(HDLEC)under normoxia and hypoxia conditions,and the microlymphangiogenesis density(MLVD)were counted.qRT-PCR was used to detect the relative expression of HIF-1αprotein and its mRNA in pancreatic cancer cell-lines of si-BANCR group and si-NC group.Results Compared with the normoxia group,significantly higher level of BANCR expression in pancreatic cancer cell-lines were observed in the hypoxia group(P<0.01).Once BANCR expression were interfered,compared with the normoxia group,the level of MLVD were significantly increased in the NC group and si-BANCR group under hypoxic conditions(P<0.001).Silencing the expression of BANCR could significantly reduce the level of MLVD in pancreatic cancer cell-lines(P<0.05);Compared with the si-BANCR group,both the mRNA and protein expression levels of HIF-1αwere significantly increased in the si-NC group under hypoxic conditions.Conclusion The expression of BANCR in pancreatic cancer cell-lines(SW1990,PANC-1)increased under hypoxic conditions,which could up-regulate the expression levels of HIF-1αat the transcription and translation,which might play an important role in pancreatic cancer microlymphangiogenesis and lymph node metastasis.
作者 郝少龙 纪宇 孙浩 纪智礼 石浩伟 马纪红 韩威 Hao Shaolong;Ji Yu;Sun Hao;Shi Haowei;Ma Jihong;Han wei(Departement of general surgery,the Affiliated Beijing Luhe hospital,Capital University of Medical Sciences;Departement of Central Laboratory,the Affiliated Beijing Luhe hospital,Capital University of Medical Sciences;Departement of Health Care Ward,the Affiliated Beijing Luhe hospital,Capital University of Medical Sciences)
出处 《中华普外科手术学杂志(电子版)》 2021年第3期262-266,共5页 Chinese Journal of Operative Procedures of General Surgery(Electronic Edition)
基金 国家自然科学基金(51973125) 北京市教委科技计划项目(KM201810025030) 北京市通州区科技计划项目(KJ2020CX006-10)。
关键词 胰腺肿瘤 细胞低氧 长链非编码RNA Pancreatic neoplasms Cell hypoxia Long non-coding RNA
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