Long non-coding RNA FOXP4-AS1 is an unfavourable prognostic factor and regulates proliferation and apoptosis in colorectal cancer
Long non-coding RNA FOXP4-AS1 is an unfavourable prognostic factor and regulates proliferation and apoptosis in colorectal cancer
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DOI：
10.1111/cpr.12312
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发表时间：
2017-02-01
影响因子：
8.5
通讯作者：
Wang, Keming
中科院分区：
文献类型：
--
作者：
Li, Juan;Lian, Yifan;Wang, Keming
目的：尽管诊断和治疗有所改进，但结直肠癌（CRC）仍然是全球第三常见的恶性肿瘤和第四大癌症相关死亡原因，并且在西方国家的发病率尤其高。最近的研究表明，长链非编码RNA（lncRNA）构成了一类新的调节肿瘤生物学过程，如增殖，凋亡和转移。在这里，我们报告，lncRNA FOXP 4-AS 1作为一个功能性癌基因在CRC发病机制。此外，我们已经试图调查FOXP 4-AS 1对肿瘤进展的影响，在体外和在vivo.Materials和方法：在这项研究中，生物信息学分析和qPCR进行调查FOXP 4-AS 1在CRC组织样本和CRC细胞系的表达。我们通过FOXP 4-S1特异性siRNA转染来抑制FOXP 4-S1的表达，并通过细胞活力和集落形成实验以及流式细胞术和乙炔脱氧尿苷（Edu）分析来评估细胞增殖。使用流式细胞术评估细胞凋亡。产生动物肿瘤异种移植物，并进行免疫组化（IHC），以评估FOXP 4-AS 1对CRC肿瘤生长的影响在vivo.Results：我们发现，FOXP 4-S1在CRC组织和细胞系中上调，其过表达与晚期病理阶段和较大的肿瘤大小呈正相关。此外，我们发现FOXP 4-AS 1敲低抑制细胞增殖并诱导细胞凋亡。在DLD-1、HT-29和HCT 116细胞系中，FOXP 4-AS 1基因敲低后，G 0/G1期细胞数明显增加，S期细胞数明显减少。结论：FOXP 4-AS 1在结直肠癌的发生发展中起重要作用，可能成为结直肠癌患者新的生物标志物。
Objectives: Despite improvements in diagnosis and treatment, colorectal cancer (CRC) remains the third most common malignancy, and fourth-leading cause of cancer-related death worldwide, and has a particularly high incidence in Western countries. Recent studies have suggested that long non-coding RNAs (lncRNAs) compose a novel class of regulators of cancer biological processes, such as proliferation, apoptosis and metastasis. Here, we report that lncRNA FOXP4-AS1 acts as a functional oncogene in CRC pathogenesis. Moreover, we have attempted to investigate the effects of FOXP4-AS1 on tumour progression, both in vitro and in vivo.Materials and methods: In this study, bioinformatic analyses and qPCR were performed to investigate FOXP4-AS1 expression in CRC tissue samples and CRC cell lines. We inhibited FOXP4-S1 expression via FOXP4-S1-specific siRNA transfection.Cell proliferation was assessed using cell viability and colony formation assays, as well as by flow cytometry and ethynyl deoxyuridine (Edu) analyses. Apoptosis was assessed using flow cytometry. Animal tumour xenografts were generated, and immunohistochemistry (IHC) was performed to evaluate effects of FOXP4-AS1 on CRC tumour growth in vivo.Results: We found that FOXP4-S1 was up-regulated in CRC tissues and cell lines and that its overexpression positively correlated with advanced pathological stages and larger tumour size. Additionally, we found that FOXP4-AS1 knockdown inhibited cell proliferation and induced apoptosis. Furthermore, FOXP4-AS1 knockdown induced marked increase in number of cells in G0/G1 phase and reduction in number of cells in S phase, in DLD-1, HT-29 and HCT116 cell lines. Consistent with these findings, FOXP4-AS1 silencing inhibited tumour growth in vivo.Conclusion: These findings suggest that FOXP4-AS1 plays a crucial role in CRC progression and may be a new biomarker in patients with CRC.