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长链非编码RNA LEF1-AS1通过miR-30-5p/SOX9轴促进结肠癌细胞的迁移、侵袭和转移。

Long Non-Coding RNA LEF1-AS1 Promotes Migration, Invasion and Metastasis of Colon Cancer Cells Through miR-30-5p/SOX9 Axis.

作者信息

Sun Ting, Liu Zhexian, Zhang Rui, Ma Siping, Lin Tao, Li Yanxi, Yang Shihua, Zhang Wanchuan, Wang Yongpeng

机构信息

Department of Blood Transfusion, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, People's Republic of China.

Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Apr 7;13:2957-2972. doi: 10.2147/OTT.S232839. eCollection 2020.

DOI:10.2147/OTT.S232839
PMID:32308428
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7156234/
Abstract

INTRODUCTION

Aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in the tumorigenesis and progression of colon cancer. Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1), a highly conserved and newly discovered long non-coding RNA, has been reported to be upregulated and correlated with poor prognosis in colon cancer, but the exact role of it remains uncertain.

MATERIALS AND METHODS

In our study, the biological functions of LEF1-AS1 in colon cancer were analyzed by cell viability assay, colony formation assay, scratch wound healing assay, transwell cell invasion assay, soft agar assay, luciferase reporter assay, pull down assay, tumor xenograft model and Western blot.

RESULTS

We found that LEF1-AS1 was upregulated in colon cancer patients and correlated with poor overall survival and recurrent-free survival. Besides, enforced expression of LEF1-AS1 in HT29 and T84 cells promoted migration, invasion, anchorage-independent growth, tumor xenograft formation and lung metastasis, while knockdown of LEF1-AS1 in COLO320 cells suppressed cell migration, invasion, anchorage-independent growth and tumor xenograft formation. In addition, LEF1-AS1 was directly interacted and inversely correlated with miR-30-5p in colon cancer, and SOX9 was a downstream target for miR-30-5p. LEF1-AS1 overexpression increased the expression level of SOX9, and restoration of SOX9 attenuated the effects caused by LEF1-AS1 knockdown in cell migration, invasion, anchorage-independent growth and tumor xenograft formation.

CONCLUSION

Our results indicated that LEF1-AS1 promoted migration, invasion and metastasis of colon cancer cells partially through miR-30-5p/SOX9 axis. The oncogenic LEF1-AS1 could be a potential prognostic biomarker for colon cancer.

摘要

引言

长链非编码RNA（lncRNAs）的异常表达与结肠癌的发生和进展有关。淋巴样增强因子1反义RNA1（LEF1-AS1）是一种高度保守且新发现的长链非编码RNA，据报道在结肠癌中上调且与预后不良相关，但其确切作用仍不确定。

材料与方法

在我们的研究中，通过细胞活力测定、集落形成测定、划痕伤口愈合测定、Transwell细胞侵袭测定、软琼脂测定、荧光素酶报告基因测定、下拉测定、肿瘤异种移植模型和蛋白质免疫印迹分析了LEF1-AS1在结肠癌中的生物学功能。

结果

我们发现LEF1-AS1在结肠癌患者中上调，且与总体生存率和无复发生存率差相关。此外，在HT29和T84细胞中强制表达LEF1-AS1可促进迁移、侵袭、非锚定依赖性生长、肿瘤异种移植形成和肺转移，而在COLO320细胞中敲低LEF1-AS1则抑制细胞迁移、侵袭、非锚定依赖性生长和肿瘤异种移植形成。此外，LEF1-AS1在结肠癌中与miR-30-5p直接相互作用且呈负相关，SOX9是miR-30-5p的下游靶点。LEF1-AS1过表达增加了SOX9的表达水平，恢复SOX9可减弱LEF1-AS1敲低在细胞迁移、侵袭、非锚定依赖性生长和肿瘤异种移植形成中所引起的作用。

结论

我们的结果表明，LEF1-AS部分通过miR-30-5p/SOX9轴促进结肠癌细胞的迁移、侵袭和转移。致癌性的LEF1-AS1可能是结肠癌潜在的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7156234/167ea7a13f3f/OTT-13-2957-g0007.jpg
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