Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and are frequently dysregulated in cancers. Here, we identify a critical lncRNA TRPM2-AS which is aberrantly expressed in gastric cancer (GC) tissues by screening The Cancer Genome Atlas Program(TCGA) database of GC cohort, and its upregulation is clinically associated with advanced pathologic stages and poor prognosis in GC patients. Silencing TRPM2-AS inhibits the proliferation, metastasis and radioresistance of GC cell whereas ectopic expression of TRPM2-AS significantly improves the progression of GC cell in multiple experiments. Mechanistically, TRPM2-AS serves as a microRNA sponge or a competitive endogenous RNA (ceRNA) for tumor suppressive microRNA miR-612 and consequently modulates the derepression of IGF2BP1 and FOXM1. Moreover, induced upregulation of IGF2BP1 subsequently increases the expression of c-Myc and promotes GC cell progression. Meanwhile, TRPM2-AS promotes the radioreistance of GC cell through enhancing the expression of FOXM1 as well. Thus, our findings support a new regulatory axis between TRPM2-AS, miR-612, IGF2BP1, or FOXM1 which serve as crucial effectors in GC tumorigenesis and malignant development, suggesting a promising therapeutic and diagnostic direction for GC.

Gastric cancer (GC) has been one of the most leading cause of cancer-death worldwide. Long non-coding RNAs (lncRNAs) have been found to be related with the carcinogenesis and the development of various cancers, including GC. However, there are still many GC-related lncRNAs functional roles and molecular mechanisms that have not yet been clearly studied. Herein, we report lncRNA CCDC144NL-AS1, which has not been explored in GC, and it is markedly upregulated in GC tissues, which may serve as an independent predictor of poor prognosis. We found that CCDC144NL-AS1 expression was significantly positively associated with a larger tumor size and more pronounced lymph node metastasis. Through a series of in vivo and in vitro functional experiments, we observed that CCDC144NL-AS1 could facilitate cell proliferation, invasion and migration and inhibit cell apoptosis in GC. Further mechanism investigation revealed that CCDC144NL-AS1 acted as a competing endogenous RNA (ceRNA) for sponging miR-143-3p and upregulated the expression of its direct endogenous target MAP3K7 in GC. Taken together, our results elucidate the oncogenic roles of CCDC144NL-AS1/miR-143-3p/MAP3K7 axis in GC progression, providing inspiration for further understanding of the mechanism of GC and making CCDC144NL-AS1 as a potential novel diagnostic and therapeutic target for GC.

Background: Increasing evidence shows that stimulated by retinoic acid 6 (STRA6) participates in regulating multiple cancers. However, the biological roles of STRA6 in gastric cancer (GC) remain unknown. This study aimed to investigate the biological function of STRA6 and reveal the underlying mechanism of its dysregulation in GC. Methods: The expression level of STRA6 was detected through quantitative real-time PCR and Western blot analysis. The effects of STRA6 on the proliferation of GC cells were studied through CCK-8 proliferation, colony formation and 5-ethynyl-2′-deoxyuridine (EdU) assays. The effects of STRA6 on migration and invasion were detected via wound healing and Transwell assays. Upstream miRNAs, which might regulate STRA6 expression, was predicted through bioinformatics analysis. Their interaction was further confirmed through dual-luciferase reporter assays and rescue experiments. Results: STRA6 was up-regulated in GC and enhanced the proliferation and metastasis of GC cells in vitro and in vivo. STRA6 knockdown could inhibit the Wnt/β-catenin signalling pathway. STRA6 was confirmed as an miR-873 target, which acted as a tumour suppressor in GC. Rescue assays showed that the repressing effect of miR-873 could be partially reversed by overexpressing STRA6. Conclusions: STRA6 is down-regulated by miR-873 and plays an oncogenic role by activating Wnt/β-catenin signalling in GC.