AUTHOR=Zhang Jian , Jiang Huali , Xie Tao , Zheng Jieling , Tian Yunhong , Li Rong , Wang Baiyao , Lin Jie , Xu Anan , Huang Xiaoting , Yuan Yawei TITLE=Differential Expression and Alternative Splicing of Transcripts Associated With Cisplatin-Induced Chemoresistance in Nasopharyngeal Carcinoma JOURNAL=Frontiers in Genetics VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00052 DOI=10.3389/fgene.2020.00052 ISSN=1664-8021 ABSTRACT=

Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard administrations applied to treat nasopharyngeal carcinoma (NPC). However, the molecular changes and functions of DDP in NPC chemo-resistance remain poorly understood. In the present study, transcriptomic sequencing between 5-8F and 5-8F/DDP cells was performed to identify differential expression and alternative splicing (AS) characteristics in DDP-resistant NPC cells. Transcriptomic profiling identified 1,757 upregulated genes and 1,473 downregulated differentially expressed genes (DEGs). Bioinformatic analysis revealed that these DEGs were associated with or participated in important biological regulatory functions in NPC. Validation of 20 significant DEGs using quantitative real-time reverse transcription PCR showed that the expression patterns of 17 mRNAs were in accordance with the sequencing data. Intron retention was identified as the major AS event in chemoresistant cells. Furthermore, the expression level of matrix metalloproteinase 1 (MMP1), which was one of the most upregulated mRNAs in the chemoresistant cell lines, was significantly associated with the migration, invasion, and proliferation of NPC cells in vitro. Our study revealed that dysregulated genes and AS-mediated DDP chemoresistance might play important roles in NPC development and progression. Targeting aberrantly expressed genes might clarify the pathogenesis of NPC and contribute to developing new therapeutic strategies for NPC.