Analysis of ceRNA network of differentially expressed genes in FaDu cell line and a cisplatin-resistant line derived from it

FaDu细胞株及其衍生的顺铂耐药株差异表达基因ceRNA网络分析

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作者:Gehou Zhang, Guolin Tan, Tieqi Li, Jingang Ai, Yexun Song, Zheng Zhou, Jian Xiao, Wei Li

Background

Hypopharyngeal cancer accounts for 2% in head and neck cancers and has a poor prognosis. Cisplatin is a widely used chemotherapeutic drug in kinds of carcinomas, concluding hypopharyngeal cancer. However, the resistance of cisplatin appeared in recent years. Cisplatin-resistance has been partly explored before, but rarely in hypopharyngeal cancer.

Conclusion

The microarray helped to find DEGs in cisplatin-resistant hypopharyngeal cancer. TNF, IL-17 and JAK-STAT signaling pathways might be more significant for cisplatin-resistance. MiR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1 might be potential genes inducing resistance.

Methods

We cultured the hypopharyngeal cancer cell (FaDu) and induced its cisplatin-resistant cell (FaDu/DDP4). Then we tested the differentially expressed genes (DEGs) between FaDu and FaDu/DDP4. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on the DEGs, and we drew the ceRNA networks of DEGs. Finally, we chose eight miRNAs and six mRNAs for qRT-PCR to verify our microarray.

Results

We induced cisplatin-resistant FaDu/DDP4 and proved its chemoresistance. The resistance index (RI) of FaDu/DDP4 was 2.828. DEGs contain 2,388 lncRNAs, 1,932 circRNAs, 745 mRNAs and 202 miRNAs. These 745 mRNAs were classified into three domains and 47 secondary GO terms. In KEGG pathway enrichment, the "TNF signaling pathway", "IL-17 signaling pathway" and "JAK-STAT signaling pathway" were potentially significant signaling pathways. Then, 52 lncRNAs, 148 circRNAs, 155 mRNAs and 18 miRNAs were selected to draw the network. We noticed several potential targets (as miR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1). At last, the eight miRNAs and six mRNAs that are critical RNAs in ceRNA network were verified by qRT-PCR.

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