Division of Cardiothoracic and vascular surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Forensic Science and Criminal Intelligence, Hubei University of Police, Wuhan, Hubei, China.
J Cell Mol Med. 2018 Dec;22(12):5862-5876. doi: 10.1111/jcmm.13856. Epub 2018 Sep 24.
Hepatocellular carcinoma (HCC) is an invasive malignant tumour and the second major cause of cancer-related deaths over the world. CRNDE and miR-217 are non-coding RNAs which play critical roles in cell growth, proliferation, migration. Mitogen-activated protein kinase 1 (MAPK1) also participates in cancer cell process. Hence, this study aimed at investigating the effect of CRNDE on migration and invasion of HCC and figuring out the role of miR-217 and MAPK1 in this process. The overexpression of CRNDE was demonstrated by a microarray-based lncRNA profiling study. CRNDE expression in HCC was verified by qRT-PCR. MTT assay and BrdU staining were applied to detect cell proliferation level. Transwell assay was utilized to examine cell migration and invasiveness abilities. Wound healing assay was performed for further exploration of cell migration capacity. MiR-217 was predicted by bioinformatics. The dual luciferase reporter assay was performed to corroborate the targeting relationship between CRNDE, miR-217 and MAPK1. MAPK1, the downstream target of miR-217, was predicted using bioinformatics and was further confirmed by qRT-PCR and Western blot. The interaction between CRNDE, miR-217 and MAPK1 was studied by qRT-PCR, Western blot, MTT, BrdU, transwell assay and wound healing assay. CRNDE was up-regulated in HCC tissues and HCC cell lines. The high expression of CRNDE facilitated cell proliferation, migration and invasion, while the inhibited one affected on the contrary. MiR-217, negatively correlated with CRNDE expression, was the target of CRNDE and was more lowly expressed in HCC. With the high expression of miR-217, HCC cell proliferation, migration and invasion were suppressed. MAPK1, the possible target of miR-217, was negatively correlated with miR-217 but positively correlated with CRNDE and had the same effect in HCC formation process as CRNDE. Long non-coding RNA CRNDE promotes the proliferation, migration and invasion of HCC cells through miR-217/MAPK1 axis.
肝细胞癌(HCC)是一种侵袭性恶性肿瘤,是全球癌症相关死亡的第二大主要原因。CRNDE 和 miR-217 是非编码 RNA,在细胞生长、增殖、迁移中发挥关键作用。丝裂原活化蛋白激酶 1(MAPK1)也参与了癌细胞过程。因此,本研究旨在探讨 CRNDE 对 HCC 迁移和侵袭的影响,并阐明 miR-217 和 MAPK1 在这一过程中的作用。基于微阵列的 lncRNA 谱分析研究证实了 CRNDE 的过表达。通过 qRT-PCR 验证了 HCC 中 CRNDE 的表达。MTT 检测和 BrdU 染色用于检测细胞增殖水平。Transwell 检测用于检测细胞迁移和侵袭能力。划痕愈合实验进一步探索了细胞迁移能力。miR-217 通过生物信息学预测。双荧光素酶报告基因实验证实了 CRNDE、miR-217 和 MAPK1 之间的靶向关系。MAPK1 是 miR-217 的下游靶点,通过生物信息学预测,并通过 qRT-PCR 和 Western blot 进一步证实。通过 qRT-PCR、Western blot、MTT、BrdU、Transwell 检测和划痕愈合实验研究了 CRNDE、miR-217 和 MAPK1 之间的相互作用。CRNDE 在 HCC 组织和 HCC 细胞系中上调。CRNDE 的高表达促进了细胞增殖、迁移和侵袭,而抑制表达则相反。miR-217 与 CRNDE 表达呈负相关,是 CRNDE 的靶标,在 HCC 中表达较低。miR-217 高表达抑制 HCC 细胞增殖、迁移和侵袭。MAPK1 是 miR-217 的可能靶点,与 miR-217 呈负相关,但与 CRNDE 呈正相关,在 HCC 形成过程中与 CRNDE 具有相同的作用。长非编码 RNA CRNDE 通过 miR-217/MAPK1 轴促进 HCC 细胞的增殖、迁移和侵袭。