Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance

Abstract

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.

Roles of NAD+ and Its Metabolites Regulated Calcium Channels in Cancer

“…It has also been reported that the inhibition of TRPM2 could accelerate the cancer cells death by increasing the intracellular ROS in non-small cell lung (NSCLC) cells [ 75 ]; the impairment of autophagy through the JNK-signaling in gastric cancer cells [ 76 ]; or reducing the G2/M ratio in the proliferation cycle of leukemia cells [ 77 ] and NSCLC cells [ 75 ]. In addition, we also noticed that recent studies have reported a novel long non-coding RNA TRPM2-AS with a high expression correlated with a larger tumor size, advanced TNM stage, and poor patient outcomes in a variety of cancers [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ]. Since its mechanisms in tumors are complicated and less related to the regulation of the signaling pathway by the ion channel, we did not review it here.…”

Knockdown of LINC00662 represses AK4 and attenuates radioresistance of oral squamous cell carcinoma

“…Long non-coding RNAs (lncRNAs), a sort of non-coding RNAs (ncRNAs), have more than 200 nucleotides in length and play crucial roles in carcinogenesis. Increasing evidence has indicated that aberrantly-expressed lncRNAs participate in cell proliferation, migration, invasion and even the radioresistance of human cancers [4][5][6]. For example, lncRNA NEAT1 promotes the radio-resistance of cervical cancer by miR-193b-3p/CCND1 axis [7]; lncRNA HOXC13-AS promotes nasopharyngeal carcinoma cell proliferation and invasion via regulating miR-383-3p/HMGA2 axis [8]; lncRNA CASC9 positively affects LIN7A expression by miR-758-3p to facilitate ovarian cancer [9]; lncRNA CASC2 downregulation promotes the postoperative local recurrence in early OSCC [10].…”

LncRNA NEAT1 Targets Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via the miR-410-3p/YY1 Axis

“…MicroRNAs (miRNAs) constitute another class of non-coding RNAs that are dysregulated in autoimmune diseases ( 10 ). LncRNA-miRNA-mRNA interactions are pivotal in various biological phenomena in oncology and immunology wherein lncRNAs have been shown to function as miRNA sponges ( 11 , 12 ). Recent studies have demonstrated that the lncRNA NEAT1 (nuclear enriched abundant transcript 1) is an oncogene that is overexpressed in multiple malignancies, including colorectal cancer ( 13 ), breast cancer ( 14 ), and leukemia ( 15 ).…”