High Expression of Long Noncoding RNA HOTAIRM1 is Associated with the Proliferation and Migration in Pancreatic Ductal Adenocarcinoma
High Expression of Long Noncoding RNA HOTAIRM1 is Associated with the Proliferation and Migration in Pancreatic Ductal Adenocarcinoma
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DOI：
10.1007/s12253-018-00570-4
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发表时间：
2019-10-01
影响因子：
2.8
通讯作者：
Xie, Xiaoliang
中科院分区：
文献类型：
--
作者：
Luo, Yongyun;He, Yaqin;Xie, Xiaoliang
胰导管腺癌是一种无法治愈的恶性肿瘤。长链非编码RNA (LncRNA) HOTAIRM1 （HOX反义基因间RNA髓系1）已被证明在几种类型癌症的进展中发挥重要作用。然而，HOTAIRM1在PDAC发展中的确切作用在很大程度上仍然未知。本研究旨在评价HOTAIRM1在PDAC的发展和进展中的潜在功能。RT-qPCR检测了47对人PDAC组织和5个PDAC细胞系中HOTAIRM1的表达。用siHOTAIRM1转染SW1990和PANC-1细胞，实现HOTAIRM1沉默。采用MTT法和集落形成法检测HOTAIRM1敲除对细胞增殖的影响。流式细胞术检测HOTAIRM1沉默对细胞周期和凋亡的影响。Transwell迁移实验探讨HOTAIRM1下调对PDAC细胞迁移潜能的影响。Western blot检测下调HOTAIRM1前后细胞周期、凋亡、迁移相关基因的表达变化。与对照组相比，HOTAIRM1在PDAC组织和细胞中的表达异常上调，并与KRAS基因突变的表达呈正相关。体外功能实验发现，转染siHOTAIRM1后，SW1990和PANC细胞株中HOTAIRM1的表达明显下调。在PDAC细胞中，HOTAIRM1敲低通过诱导细胞周期阻滞于G0/G1期来减弱细胞增殖，促进细胞凋亡，并通过调节相关基因表达来抑制细胞迁移。综上所述，HOTAIRM1在PDAC进展中起关键作用，可能成为胰腺导管腺癌新的诊断和合理的治疗靶点。
Pancreatic ductal adenocarcinoma (PDAC) is an incurable malignancy. Long noncoding RNA (LncRNA) HOTAIRM1 (HOX antisense intergenic RNA myeloid 1) has been shown to play important roles in the progression of several type cancers. However, the exact role of HOTAIRM1 in PDAC development remains largely unknown. This study aims to evaluate the potential function of HOTAIRM1 in the development and progress of PDAC. HOTAIRM1 expression was measured by RT-qPCR in forty seven paired human PDAC tissues and five PDAC cell lines. SW1990 and PANC-1 cells were transfected with siHOTAIRM1 to achieve HOTAIRM1 silence. MTT assay and colony formation assay were used to detect the effect of HOTAIRM1 knockdown on cell proliferation. The impact of HOTAIRM1 silence on cell cycle and apoptosis was assessed by flow cytometry assay. Transwell migration assay was performed to explore the influence of HOTAIRM1 downregulation on the migratory potential of PDAC cells. Western blot assay was applied to determine the expression changes of cell cycle, apoptosis, and migration-related genes before and after downregulating HOTAIRM1. HOTAIRM1 expression was abnormally upregulated in PDAC tissues and cells when compared with the control samples, and was positively associated with the expression of KRAS gene mutation. In vitro functional experiments, HOTAIRM1 expression was significantly downregulated by transfection with siHOTAIRM1 in SW1990 and PANC cell lines. HOTAIRM1 knockdown attenuated cell proliferation by inducing cell cycle arrest at G0/G1 phase, promoted cell apoptosis, and inhibited cell migration in PDAC cells by regulating related-genes expression. In conclusion, HOTAIRM1 plays a critical role in PDAC progression, which may be a novel diagnostic and rational therapeutic target for the treatment of pancreatic ductal adenocarcinoma.