非编码 RNA MFI2-AS1 通过 miR-574-5p/MYCBP 轴促进结直肠癌细胞增殖、迁移和侵袭。

Non-coding RNA MFI2-AS1 promotes colorectal cancer cell proliferation, migration and invasion through miR-574-5p/MYCBP axis.

机构信息

Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China.

出版信息

Cell Prolif. 2019 Jul;52(4):e12632. doi: 10.1111/cpr.12632. Epub 2019 May 16.

DOI:10.1111/cpr.12632

PMID:31094023

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6668983/

Abstract

OBJECTIVE

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play essential roles in the tumour progression. LncRNAs mostly act as competing endogenous RNAs (ceRNAs) by sponging miRNAs. This study aimed to study the association of a novel lncRNA MFI2-AS1 with miR-574-5p/MYCBP axis in the development of colorectal cancer (CRC).

METHODS

Ninety-four CRC tissues and paired adjacent non-tumour tissues were included in our study. The relative expression level of MFI2-AS1 was detected, and its relationship with clinico-pathological factors was analysed. Then, the CRC cells lines (LoVo and RKO) were transfected with MFI2-AS1 siRNA, miR-574-5p mimics and inhibitors. Cell proliferation, migration, invasion, cell cycle distribution and DNA damage in response to different transfection conditions were examined. Dual-luciferase reporter assay was performed to identify the target interactions between MFI2-AS1 and miR-574-5p, miR-574-5p and MYCBP.

RESULTS

LncRNA MFI2-AS1 and MYCBP were up-regulated in CRC tissues when compared with adjacent non-tumour tissues. The expression levels of MFI2-AS1 were significantly associated with tumour histological grade, lymph and distant metastasis, TNM stage and vascular invasion. Both MFI2-AS1 siRNA and miR-574-5p mimics inhibited proliferation, migration and invasion in LoVo and RKO cells. The transfection of miR-574-5p inhibitor showed MFI2-AS1 siRNA-induced changes in CRC cells. Dual-luciferase reporter assay revealed target interactions between MFI2-AS1 and miR-574-5p, miR-574-5p and MYCBP.

CONCLUSIONS

These findings suggested that lncRNA MFI2-AS1 and MYCBP have promoting effects in CRC tissues. LncRNA MFI2-AS1 promoted CRC cell proliferation, migration and invasion through activating MYCBP and by sponging miR-574-5p.

摘要

目的

长链非编码 RNA（lncRNA）和 microRNA（miRNA）在肿瘤进展中发挥重要作用。lncRNA 主要通过海绵吸附 miRNA 作为竞争性内源 RNA（ceRNA）发挥作用。本研究旨在研究新型 lncRNA MFI2-AS1 与 miR-574-5p/MYCBP 轴在结直肠癌（CRC）发生发展中的关系。

方法

本研究纳入 94 例 CRC 组织及配对癌旁非肿瘤组织。检测 MFI2-AS1 的相对表达水平，并分析其与临床病理因素的关系。然后，用 MFI2-AS1 siRNA、miR-574-5p 模拟物和抑制剂转染 CRC 细胞系（LoVo 和 RKO）。检测不同转染条件下细胞增殖、迁移、侵袭、细胞周期分布和 DNA 损伤情况。采用双荧光素酶报告基因实验鉴定 MFI2-AS1 与 miR-574-5p、miR-574-5p 与 MYCBP 的靶基因相互作用。

结果

与癌旁非肿瘤组织相比，CRC 组织中 lncRNA MFI2-AS1 和 MYCBP 表达上调。MFI2-AS1 的表达水平与肿瘤组织学分级、淋巴和远处转移、TNM 分期和血管浸润显著相关。MFI2-AS1 siRNA 和 miR-574-5p 模拟物均抑制 LoVo 和 RKO 细胞的增殖、迁移和侵袭。转染 miR-574-5p 抑制剂显示 MFI2-AS1 siRNA 诱导 CRC 细胞发生变化。双荧光素酶报告基因实验显示 MFI2-AS1 与 miR-574-5p、miR-574-5p 与 MYCBP 之间存在靶基因相互作用。