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

Miao,Wen‑Jie; Yuan,Dong‑Jie; Zhang,Guo‑Zheng; Liu,Qi; Ma,Hui‑Min; Jin,Qian‑Qian

doi:10.3892/or.2018.6941

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

Authors:
- Wen‑Jie Miao
- Dong‑Jie Yuan
- Guo‑Zheng Zhang
- Qi Liu
- Hui‑Min Ma
- Qian‑Qian Jin
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Affiliations: Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
Published online on: December 19, 2018 https://doi.org/10.3892/or.2018.6941
Pages: 1797-1806

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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.

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