Despite many advances in the diagnosis and treatment of gastric cancer (GC), the prognosis of patients with GC remains poor. Circular RNAs (circRNAs), a new star of the non-coding RNA network, have been identified as critical regulators in various cancers. There is increasing evidence that circRNAs represent a class of widespread and diverse endogenous RNAs that may regulate gene expression. However, the role of circRNAs in GC remains elusive. Here, we aimed to determine the circRNA expression profile and investigate the functional and prognostic significance of circRNA in GC.
In this study, we investigated the expression profile of circRNAs in three GC samples and paired adjacent normal tissues using ribo-minus RNA sequencing and a bioinformatics analysis. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to identify circRNA candidates. Molecular and cellular techniques were used to explore the biological function and mechanism of circRNA in GC cells. The prognostic significance was analyzed using the Kaplan-Meier method and the Cox proportional hazards model.
We first characterized circular RNA transcripts using RNA-seq analysis of ribosomal RNA-depleted total RNA from three paired normal and cancerous gastric tissues. In all, 15623 distinct circRNA candidates were found in these tissues and at least 5500 distinct circRNAs are differently expressed in GC tissues compared with matched normal tissues. We further characterized one abundant circRNA derived from the LMTK2 gene, termed circLMTK2. The expression of circLMTK2 is often upregulated in GC tissues and the silencing of circLMTK2 significantly inhibits gastric cancer cell growth. Furthermore, the level of circLMTK2 was observed as an independent prognostic marker for overall survival and disease-free survival of patients with GC.
Our study revealed the circular RNA profile of GC tissues and characterized a differentially expressed circRNA derived from the LMTK2 gene. circLMTK2 may serve as a new proliferative factor and prognostic marker in gastric cancer.
Clinical trial identification
Legal entity responsible for the study
Fudan University Shanghai Cancer Center
All authors have declared no conflicts of interest.