DLG1-AS1 由 MYC 激活，并通过 miR-497-5p/SSRP1 轴驱动肝癌细胞的增殖和迁移。

DLG1-AS1 is activated by MYC and drives the proliferation and migration of hepatocellular carcinoma cells through miR-497-5p/SSRP1 axis.

作者信息

Min Jie, Jin Dayong, Zhang Feng, Kang Yanxia, Qi Yuhong, Du Pang

机构信息

Department of Oncology, Tangdu Hospital, Xi'an, 710038, Shaanxi, China.

Department of Radiology, Tangdu Hospital, Xi'an, 710038, Shaanxi, China.

出版信息

Cancer Cell Int. 2021 Jan 6;21(1):16. doi: 10.1186/s12935-020-01667-0.

BACKGROUND

Long non-coding RNAs (lncRNAs) have been reported to be biological regulators in hepatocellular carcinoma (HCC). DLG1 antisense RNA 1 (DLG1-AS1) has been found to be up-regulated in cervical cancer. However, its function and underlying mechanism in HCC remains unknown.

METHODS

DLG1-AS1 expression was assessed in HCC cells and normal cell by RT-qPCR. Luciferase reporter assay, RNA pull down assay and RIP assay were used to demonstrate the interaction between DLG1-AS1 and miR-497-5p.

RESULTS

DLG1-AS1 was highly expressed in HCC cells. Silencing of DLG1-AS1 led to the inhibition of HCC cell growth and migration. Besides, MYC induced the transcriptional activation of DLG1-AS1. MYC could facilitate HCC cellular processes by up-regulating DLG1-AS1. MiR-497-5p could interact with DLG1-AS1 in HCC cells. Down-regulation of miR-497-5p could reverse the impacts of DLG1-AS1 silencing on HCC cells. SSRP1 expression could be positively regulated by DLG1-AS1 but was negatively regulated by miR-497-5p. Knockdown of DLG1-AS1 suppressed tumor growth in nude mice.

CONCLUSIONS

DLG1-AS1 is activated by MYC and functions as an oncogene in HCC via miR-497-5p/SSRP1 axis.

背景

长链非编码RNA（lncRNAs）已被报道为肝细胞癌（HCC）中的生物调节因子。DLG1反义RNA 1（DLG1-AS1）在宫颈癌中被发现上调。然而，其在HCC中的功能及潜在机制仍不清楚。

方法

通过RT-qPCR评估HCC细胞和正常细胞中DLG1-AS1的表达。采用荧光素酶报告基因检测、RNA下拉检测和RNA免疫沉淀检测来证明DLG1-AS1与miR-497-5p之间的相互作用。

结果

DLG1-AS1在HCC细胞中高表达。沉默DLG1-AS1导致HCC细胞生长和迁移受到抑制。此外，MYC诱导DLG1-AS1的转录激活。MYC可通过上调DLG1-AS1促进HCC细胞进程。miR-497-5p可在HCC细胞中与DLG1-AS1相互作用。下调miR-497-5p可逆转DLG1-AS1沉默对HCC细胞的影响。SSRP1表达可被DLG1-AS1正向调节，但被miR-497-5p负向调节。敲低DLG1-AS1可抑制裸鼠肿瘤生长。