Abstract
Purpose: Numerous studies have shown that lncRNAs play vital roles in the development and progression of cancer. However, investigations of lncRNAs in gastric cancer are limited and need to be further pursued.Materials and Methods: According to RNA-seq results of gastric cancer (GC) tissues, we identified a novel lncRNA, C1RL-AS1. qRT-PCR was used to detect the expression level of C1RL-AS1 in paired GC and normal tissues. Nuclear/cytoplasmic fractionation was applied to evaluate the distribution of C1RL-AS1 in GC cells. For functional evaluation, CCK-8, colony formation, transwell, and apoptosis assays were used to determine the oncogenic role of C1RL-AS1.Results: C1RL-AS1 was upregulated in GC tissues, and high expression levels of C1RL-AS1 were associated with poor prognosis. Further in vitro functional assays revealed that silencing C1RL-AS1 attenuated the proliferation rate and migration ability and enhanced the apoptotic rate and the senescence of GC cells. The subsequent underlying mechanistic investigation revealed that Wnt/β-catenin was involved in C1RL-AS1-mediated signaling. Rescue experiments suggested that C1RL-AS1 probably promoted the malignant phenotype via the AKT/β-catenin pathway by downregulating c-Myc.Conclusions: C1RL-AS1 probably exerts its biological function by mediating the AKT/β-catenin/c-Myc pathway, indicating a novel therapeutic target in GC.
Highlights
Gastric cancer is one of the most common malignant tumors in humans; its incidence ranks fifth, and its mortality ranks third worldwide [1]
LncRNA C1RL-AS1 was dramatically upregulated according to the RNA-seq data
C1RL-AS1 expression was evaluated in gastric cancer data from the TCGA database
Summary
Gastric cancer is one of the most common malignant tumors in humans; its incidence ranks fifth, and its mortality ranks third worldwide [1]. In China, there were ∼679,000 new cases and 498,000 deaths from gastric cancer in 2015 [2]. Urgent efforts are needed to discover new biomarkers for the early diagnosis and treatment of gastric cancer [3]. The aberrant expression of lncRNAs is usually associated with many biological events in cancer progression [7,8,9]. LncRNA EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolism in cancer [11]. Our previous study showed that onclncRNA626 promotes malignant behavior in gastric cancer by interacting with SRSF1 [12]
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