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.

中文翻译：

---

长的非编码RNA TRPM2-AS充当miR-612的microRNA海绵，可促进胃癌的进展和放射抗性。

长的非编码RNA（lncRNA）逐渐成为肿瘤发生的重要调节剂，并且在癌症中经常失调。在这里，我们通过筛选GC队列的癌症基因组图谱计划（TCGA）数据库，鉴定了在胃癌（GC）组织中异常表达的关键lncRNA TRPM2-AS，其上调与晚期病理分期和预后不良相关。 GC患者。沉默TRPM2-AS可抑制GC细胞的增殖，转移和放射抵抗，而异位表达的TRPM2-AS可在多个实验中显着改善GC细胞的进程。从机制上讲，TRPM2-AS可用作抑癌性microRNA miR-612的microRNA海绵或竞争性内源RNA（ceRNA），因此可调节IGF2BP1和FOXM1的抑制。此外，诱导的IGF2BP1上调随后增加c-Myc的表达并促进GC细胞进程。同时，TRPM2-AS还通过增强FOXM1的表达来促进GC细胞的放射抗性。因此，我们的发现支持TRPM2-AS，miR-612，IGF2BP1或FOXM1之间的新调控轴，它们在GC肿瘤发生和恶性发展中起着至关重要的作用，这为GC的治疗和诊断方向指明了希望。