Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

Wang,Ping; Cui,Jiayue; Wen,Jihong; Guo,Yunhui; Zhang,Liangzi; Chen,Xia

doi:10.3892/ol.2016.5288

Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

Authors:
- Ping Wang
- Jiayue Cui
- Jihong Wen
- Yunhui Guo
- Liangzi Zhang
- Xia Chen
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Affiliations: Department of Otolaryngology‑Head and Neck Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Histology and Embryology, College of Basic Medical Sciences Jilin University, Changchun, Jilin 130021, P.R. China, Department of Gynaecology and Obstetrics, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: October 18, 2016 https://doi.org/10.3892/ol.2016.5288
Pages: 4605-4612
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cisplatin has been used effectively in the treatment of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) were recently reported to contribute to the pathogenesis and progression of HCC. Their molecular mechanism related to cisplatin treatment remains unclear. The purpose of this study is to identify specific lncRNAs and to clarify their functions in HCC after cisplatin exposure. Reannotation and identification of differentially expressed lncRNAs were performed using the microarray data set GSE38122 in the Gene Expression Omnibus database. Four significantly differentially expressed lncRNAs (RP11‑134G8.8, RP11‑612B6.2, RP11‑363E7.4 and RP1‑193H18.2) were identified in HepG2 cells exposed to cisplatin by bioinformatics methods. The upregulated RP11‑134G8.8 and RP11‑363E7.4 and the downregulated RP1‑193H18.2 were confirmed by reverse transcription‑quantitative polymerase chain reaction. Furthermore, 57 significant co‑expressing genes and their corresponding pathways were annotated and identified. The p53 signaling pathway showed the most significant difference among all pathways. Based on these results, the cell cycle and three key genes, cyclin‑dependent kinase inhibitor 1A (CDKN1A, also known as p21), tumor protein p53 inducible protein 3 (TP53I3) and wild‑type p53‑induced phosphatase 1 (Wip1, also known as PPM1D), were examined. CDKN1A, TP53I3 and PPM1D were all downregulated by RP1‑193H18.2 but upregulated by RP11‑134G8.8 and RP11‑363E7.4. And obvious S phase arrest was induced by cisplatin treatment for 24 h in HepG2 cells. Finally, the immunofluorescence results showed upregulation of TP53I3 and Wip1 and downregulation of p21 at the protein level. The results suggested that the lncRNAs RP11‑134G8.8, RP11‑363E7.4 and RP1‑193H18.2, and their co‑expression genes, which annotated into the p53 signaling pathway, could be potential targets for cisplatin treatment.

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