RETRACTED ARTICLE: LINC00355 induces gastric cancer proliferation and invasion through promoting ubiquitination of P53

Wenjing Zhao,Qianlu Yang,Yuanyuan Chen,Wei De,Xinying Huo,Jinfei Chen,Juxue Li,Fen Yang,Yan Jin,Peng Wu,Jian Yang

doi:10.1038/s41420-020-00332-9

Wenjing Zhao, Qianlu Yang + Show 9 more

Open Access

https://doi.org/10.1038/s41420-020-00332-9

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Abstract

Long noncoding RNAs (LncRNAs) have been reported to play critical roles in gastric cancer, but true biomarkers remain unknown. In this study, we found a new lncRNA LINC00355 that was involved in malignant progression of gastric cancer (GC) and further revealed its role and mechanism. Differentially expressed lncRNAs were identified through bioinformatics, and qRT-PCR was used to validate the expression of LINC00355 in gastric cancer tissues and cells. The biological role of LINC00355 in GC was detected by gene overexpression and knockdown experiments. Subcellular fractionation, qRT-PCR, and FISH were performed to detect the subcellular localization. Co-IP and western blotting were used to study the ubiquitination-mediated regulation of P53 and the expression of the E3 ligases RAD18 and UBE3C. The results showed that LINC00355 was significantly increased in gastric cancer cell lines and patient tissues and closely correlated with late stages, distant metastasis, and poor prognosis of patients. High expression of LINC00355 promoted the proliferation and invasion of gastric cancer cells in vivo and in vitro. Mechanistic studies found that LINC00355 that mainly located in the nucleus, acting as a transcriptional activator, promoted transcription of RAD18 and UBE3C, which both bind to P53 and mediate the ubiquitination and degradation of P53. Furthermore, LINC00355 overexpression enhanced the ubiquitination process, and LINC00355 knockdown alleviated it. These results indicated that LINC00355 induces gastric cancer cell proliferation and invasion by promoting transcription of RAD18 and UBE3C, which mediates ubiquitination of P53 and thereby plays a critical role in survival and tumorigenicity of gastric cancer cells. LINC00355 may represent a new mechanism for GC progression and provide a potential marker for GC diagnosis and treatment.

Highlights

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related death worldwide[1]
A previous study reported that FEZF1-AS1 promoted gastric cancer cell proliferation and that high expression of FEZF1-AS1 predicted poor prognosis in gastric cancer patients[24]
We found that 167 lncRNAs in GSE27342, 18 lncRNAs in GSE58828, and 310 lncRNAs in The Cancer Genome Atlas (TCGA) were downregulated, and that LINC00982 was the only overlapping lncRNA (Fig. 1b, right panel)

Summary

Introduction

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related death worldwide[1]. As common epigenetic regulatory molecules, lncRNAs play an important role in epigenetics and are involved in transcriptional regulation, RNA shearing and modification, mRNA stabilization, translational regulation, protein stabilization and transport, chromosome formation, and structural stability[7,8]. They participate in regulating embryo development, tissue. Zhao et al Cell Death Discovery (2020)6:99 differentiation, organ formation, and the occurrence and development of some diseases[9,10]. The dysregulation of lncRNAs can promote tumorigenesis and enhance the development of cancer by regulating proliferation, invasion, and metastasis[11,12]

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