Long noncoding RNA FAM225A promotes the malignant progression of gastric cancer through the miR-326/PADI2 axis

Xiang Ma,Li Yang,Yuanhang Wang,Gang Wang,Zekuan Xu,Hao Fan,Kuan Shen,Jian Xiao,Kanghui Liu,Peidong Ni,Wangwang Chen,Zengliang Li

doi:10.1038/s41420-021-00809-1

Xiang Ma, Li Yang + Show 10 more

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https://doi.org/10.1038/s41420-021-00809-1

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Abstract

Gastric cancer (GC) is a global health problem and further studies of its molecular mechanisms are needed to identify effective therapeutic targets. Although some long noncoding RNAs (lncRNAs) have been found to be involved in the progression of GC, the molecular mechanisms of many GC-related lncRNAs remain unclear. In this study, a series of in vivo and in vitro assays were performed to study the relationship between FAM225A and GC, which showed that FAM225A levels were correlated with poor prognosis in GC. Higher FAM225A expression tended to be correlated with a more profound lymphatic metastasis rate, larger tumor size, and more advanced tumor stage. FAM225A also promoted gastric cell proliferation, invasion, and migration. Further mechanistic investigation showed that FAM225A acted as a miR-326 sponge to upregulate its direct target PADI2 in GC. Overall, our findings indicated that FAM225A promoted GC development and progression via a competitive endogenous RNA network of FAM225A/miR-326/PADI2 in GC, providing insight into possible therapeutic targets and prognosis of GC.

Highlights

Gastric cancer (GC) is mainly concentrated in Asia, including China, Japan, and the Republic of Korea
FAM225A is upregulated in GC and predicts a poor prognosis FAM225A was identified by analyzing the human microarray dataset GSE79973 from the Gene Expression Omnibus (GEO) database and RNA sequencing (RNA-seq) data from The Cancer
Most human genomes are transcribed into noncoding RNAs (ncRNAs), whereas protein coding genes account for a small proportion; this has been confirmed by the Encyclopedia of DNA Elements (ENCODE) Project Consortium [26]

Summary

Introduction

Gastric cancer (GC) is mainly concentrated in Asia, including China, Japan, and the Republic of Korea. 50% of patients with GC in China are at a locally advanced stage, which seriously affects national health [1, 2]. LncRNAs function in the cell by epigenetic, transcriptional, or posttranscriptional mechanisms [11,12,13]. Unlike other noncoding RNAs (ncRNAs), such as small interfering RNAs (siRNAs) and microRNAs (miRNAs), the regulatory mechanisms of lncRNAs appear to be more complex. Through these mechanisms, lncRNAs act as oncogenes or tumor suppressor genes to regulate tumor cell proliferation, metastasis, and drug resistance [14]. The complex interactions between mRNA and ncRNAs, such as lncRNAs, have been described as competitive endogenous RNA (ceRNA)

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