The lncRNA TERC promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-423-5p to regulate SOX12 expression

Abstract

Background: Long non-coding RNAs (lncRNAs) play critical roles in gastric cancer (GC) initiation progression. However, the biological function of the lncRNA telomerase RNA component (TERC) remains unknown in human GC. The present study sought to determine the biological function and underlying molecular mechanism of the lncRNA TERC in GC progression. Methods:The expression levels of the lncRNA TERC in GC tissues and cell lines were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of the lncRNA TERC on the proliferation, migration, and invasion of GC cells were determined using Cell Counting Kit-8 (CCK-8) and Transwell assays. Dual luciferase reporter and argonaute 2 (AGO2)-RNA immunoprecipitation (RIP) assays were used to detect the binding between the lncRNA TERC and microRNA-423-5p (miR-423-5p).Western blotting was performed to measure the expression levels of sex determining region Y-box 12 (SOX12), N-cadherin, E-cadherin, matrix metallopeptidase 9 (MMP9), and proliferating cell nuclear antigen (PCNA). Results:The results demonstrated that the lncRNA TERC expression levels were upregulated in GC cells and tissues, while miR-423-5p expression levels were downregulated. The upregulation of the lncRNA TERC was associated with a shorter overall survival in patients with GC. The knockdown of the lncRNA TERC significantly reduced the proliferation, migration, and invasion of human GC cell lines HGC-27 and SNU-1 cells. Further, the lncRNA TERC knockdown in the HGC-27 and SNU-1 cells significantly downregulated the expression levels of SOX12, N-cadherin, MMP9, and PCNA, and upregulated the expression levels of miR-423-5p and E-cadherin. MiR-423-5p was also identified as a target of the lncRNA TERC and was found to directly bind to the lncRNA TERC. Additionally, miR-423-5p was found to directly target SOX12 to inhibit the proliferation, migration, and invasion of the HGC-27 and SNU-1 cells. Conclusions:In conclusion, the findings of this study suggested that the lncRNA TERC may regulate the miR-423-5p/SOX12 signaling axis by directly sponging miR-423-5p and inhibiting SOX12 expression, thereby leading to the progression of GC. These findings may reveal novel targets for future GC therapy.

In Silico Bioinformatics Analysis on the Role of Long Non-Coding RNAs as Drivers and Gatekeepers of Androgen-Independent Prostate Cancer Using LNCaP and PC-3 Cells

“…The LncSEA analysis revealed that TERC was hypermethylated (Figure 4G) and that it interacts with several miRNAs, especially tumour-suppressive miRNAs (Figure 4A). Although this study is the first to report TERC hypermethylation and sponging of the tumour-suppressor miRNA-320 family in PCa, similar TERC oncogenic mechanisms have been reported in gastric cancer, where TERC was shown to sponge miR-423-5p, thus promoting the proliferation of gastric cancer [42]. TERC upregulation in PC-3 cells is further supported by RNA-sequencing data, where in normal prostate epithelia, its expression is −16.61 [43].…”

Experimental Identification of Aberrantly Expressed Long Non-Coding RNAs in Breast Cancer

“…TERC (telomerase RNA component) serves as a template for telomere replication catalyzed by the telomerase enzyme, which contributes to the uncontrolled proliferation of cancer cells. Despite the fact that our experimental data were not confirmed by the data of the GEPIA database for breast cancer, an increase in TERC expression was shown for gastric cancer [17], and TERC was proposed as a diagnostic marker in cervical cancer [18] and lung cancer [19]. MEG3 (maternally expressed 3) is a relatively well-studied lncRNA demonstrating oncosuppressive properties.…”