lncRNA CASC2/miR‑18a‑5p axis regulates the malignant potential of nasopharyngeal carcinoma by targeting RBBP8

Abstract

Nasopharyngeal carcinoma (NPC) is a prevalent head and neck tumor which has a high mortality rate in Southeast Asia, especially in Southern China. Cancer susceptibility candidate 2 (CASC2) is a newly identified long non-coding RNA (lncRNA) that has been found to play a suppressive role in several types of tumors. However, the expression and functional role of CASC2 in NPC are still unclear. In the present study, using NPC tissues, cells and transplanted mice, we investigated the mechanism of CASC2-mediated regulation of NPC. We showed that the CASC2 level is reduced in NPC tissues and cells. CASC2 downregulation promoted proliferation and inhibited apoptotic cell death in NPC cells. In contrast, CASC2 upregulation inhibited proliferation and increased apoptosis. There were putative binding sites of microRNA (miR)-18a-5p in the promoter of CASC2. The level of miR-18a-5p was upregulated in NPC tissues and cells. We further confirmed that CASC2 could directly bind with miR-18a-5p and inhibit miR-18a-5p expression, using reporter gene and RNA immunoprecipitation assays. miR-18a-5p suppressed CASC2 upregulation-mediated decrease in proliferation and increase in apoptotic cell death. Bioinformatics predicted the putative binding site of miR-18a-5p in the 3' untranslated region of C-terminal binding protein interacting protein (CtIP)/RBBP8. It was further confirmed that miR-18a-5p could directly bind with RBBP8 and inhibit RBBP8 expression. Downregulation of RBBP8 inhibited the anti-miR-18a-5p-mediated increase in apoptosis and decrease in proliferation. Downregulation of CASC2 increased tumor growth, increased the level of miR-18a-5p and decreased RBBP8 expression in vivo. In summary, CASC2 regulates NPC malignancy through modulation of RBBP8 via sponging miR-18a-5p. Our findings highlight the CASC2/miR-18a-5p/RBBP8 axis in NPC pathogenesis and provide new biomarkers and potential targets for the therapy of NPC. lncRNA CASC2/miR-18a-5p axis regulates the malignant potential of nasopharyngeal carcinoma by targeting RBBP8

Integrative Bioinformatics Approaches to Map Potential Novel Genes and Pathways Involved in Ovarian Cancer

“…The research group led by Rose et al suggested that RBBP8 was significantly hypermethylated in bladder cancer (BLCA) and was associated with more prolonged overall survival, and they indicated that it may be used as a complementary marker for the detection of BLCA in urine (Mijnes et al, 2018). Miao et al (2019) reported that the downregulation of the long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2, enhanced tumor development, increased miR-18a-5p levels, and reduced the expression of RBBP8 in nasopharyngeal carcinoma (NPC). The upregulation of CASC2 resulted in decreased proliferation and increased apoptotic cell death in vivo (Miao et al, 2019).…”

“…Miao et al (2019) reported that the downregulation of the long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2, enhanced tumor development, increased miR-18a-5p levels, and reduced the expression of RBBP8 in nasopharyngeal carcinoma (NPC). The upregulation of CASC2 resulted in decreased proliferation and increased apoptotic cell death in vivo (Miao et al, 2019). Our data clearly showed that RBBP8 was differentially expressed and involved in cell cycle regulation (Supplementary Figure 1B).…”

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

“…lncRNA cancer susceptibility candidate 2 (CASC2) could inhibit proliferation, induce apoptosis through inhibiting the activation of miR-18a-5p/RB binding protein 8 (RBBP8) axis. 208 MiR-324-3p can inhibit the invasion of tumor cells through its suppression of Homo sapiens GLI family zinc-finger 3 (GLI3) gene expression. 209 High expressions of miR-7 inhibit the , and E-cadherin.…”

Associations among Genetic Variants and Intracranial Aneurysm in a Chinese Population

“…RBBP8 is located at chromosome 18q11.2 and may be a tumor suppressor 39. Conflicting results have been reported for RBBP8 variants in relation to IA in previous GWASs.…”