Long non‑coding RNA CASC15 facilitates esophageal squamous cell carcinoma tumorigenesis via decreasing SIM2 stability via FTO‑mediated demethylation

Qin,Bo; Dong,Meng; Wang,Zhengyang; Wan,Jiajia; Xie,Yingying; Jiao,Yi; Yan,Dan

doi:10.3892/or.2020.7917

Long non‑coding RNA CASC15 facilitates esophageal squamous cell carcinoma tumorigenesis via decreasing SIM2 stability via FTO‑mediated demethylation

Authors:
- Bo Qin
- Meng Dong
- Zhengyang Wang
- Jiajia Wan
- Yingying Xie
- Yi Jiao
- Dan Yan
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Affiliations: Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Yongcheng Coal & Electricity Holding Group Co., Ltd., Shangqiu, Henan 476000, P.R. China
Published online on: December 30, 2020 https://doi.org/10.3892/or.2020.7917
Pages: 1059-1071
Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNAs (lncRNAs) are involved in the regulation of esophageal squamous cell carcinoma (ESCC) progression. However, the function and mechanism of lncRNA cancer susceptibility candidate 15 (CASC15) are poorly defined. In the present study, tumor and normal adjacent tissues were collected from 45 patients with ESCC. Expression levels of CASC15, fat mass and obesity‑associated (FTO) protein and single‑minded 2 (SIM2) were examined via reverse transcription‑quantitative PCR and western blot assays. Cell proliferation and apoptosis were evaluated via MTT, flow cytometry and caspase‑3 activity assays, respectively. Additionally, an ESCC mouse xenograft model was used to assess the function of CASC15 in vivo. The interaction between FTO and CASC15/SIM2 was analyzed via RNA immunoprecipitation and RNA pull‑down assays. The results revealed that CASC15 expression was elevated in ESCC tissues, and patients with ESCC exhibiting high CASC15 expression had a poor prognosis. CASC15‑knockdown inhibited ESCC cell proliferation and facilitated apoptosis. Additionally, CASC15‑knockdown decreased the growth of ESCC xenograft tumors. CASC15 decreased SIM2 stability via FTO‑mediated demethylation. Additionally, FTO loss markedly weakened CASC15‑mediated pro‑proliferative and anti‑apoptotic effects in ESCC cells. SIM2 downregulation weakened the effect of CASC15‑knockdown on cell proliferation and inhibited the increase of the apoptotic rate and caspase‑3 activity induced by CASC15 depletion in ESCC cells. In conclusion, CASC15 promoted ESCC tumorigenesis by decreasing SIM2 stability via FTO‑mediated demethylation.

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