Long intergenic non-coding RNA 00473 promotes proliferation and migration of gastric cancer via the miR-16-5p/CCND2 axis and by regulating AQP3

Shuaishuai Zhuo,Tianshi Ma,Hongxia Li,Die Lu,Shihao Di,Rumeng Bai,Zigui Zou,Miaomiao Sun,Zhihong Zhang

doi:10.1038/s41419-021-03775-9

Abstract

Gastric cancer (GC) is one of the most common malignancies worldwide, but its molecular mechanisms remain unclear. Increasing evidence indicates that long non-coding RNAs (LncRNAs) play a pivotal role in various cancers recently. Our present study focused on exploring the function of long intergenic non-coding RNA 00473 (LINC00473) in GC. In this study, we found that LINC00473 expression was aberrantly increased in tumor tissues compared with the paired para-cancerous tissues. The expression of high LINC00473 in GC was notably correlated with a higher risk of lymphatic metastasis, a higher incidence of vascular cancer embolus, and advanced TNM stage. Further experiments showed that the overexpression of LINC00473 could promote the proliferation and metastasis of GC cells both in vitro and in vivo. The apoptosis of GC cells increased significantly by the decrease of LINC00473. Mechanistically, LINC00473 could sponge miR-16-5p in the cytoplasm and relieve its suppression of CCND2. Moreover, AQP3 was found to be a significant downstream target gene for LINC00473 through RNA transcriptome sequencing, as demonstrated by qRT-PCR and western blot. Overexpression of LINC00473 can partially reverse the effects of AQP3 decrease on GC proliferation and metastasis. LINC00473 regulated AQP3 expression through CREB was confirmed by western blot. Our research indicates that LINC00473/miR-16-5p/CCND2 axis plays a role in the proliferation of GC and modulates AQP3 to influence GC cell metastasis, making it a potential therapeutic target for GC.

Highlights

Gastric cancer (GC) is one of the most common malignancies worldwide and the second leading cause of cancerrelated death in China[1,2]
long non-coding RNAs (LncRNAs)-GMAN was significantly upregulated in hepatocellular carcinoma (HCC), which can increase the phosphorylation of eukaryotic translation initiation factor 4B to promote metastasis and inhibit apoptosis in HCC7
The expression of LINC00473 was detected in 53 GC tumor tissues compared to corresponding para-carcinoma tissues by qRT-PCR

Summary

Introduction

Gastric cancer (GC) is one of the most common malignancies worldwide and the second leading cause of cancerrelated death in China[1,2]. In the United States, a significant proportion of patients with GC are diagnosed as late, unfit for surgical treatment, and have an extremely low 5-year overall survival rate[3]. Long non-coding RNAs (LncRNAs), as a subclass of noncoding RNA of which was transcribed from more than 90% of the genome sequences, can regulate the pathogenesis of various cancers at multiple levels, including GC4–6. LncRNAs can influence gene regulation through a number of mechanisms, including epigenetic, transcriptional, and post-transcriptional levels, to influence the progression of cancer. As a competing endogenous RNA (ceRNA) of microRNA miR-101, Official journal of the Cell Death Differentiation Association

Methods

Results

Conclusion