Differential Expression and Alternative Splicing of Transcripts Associated With Cisplatin-Induced Chemoresistance in Nasopharyngeal Carcinoma

Frontiers in Genetics

Xiaoting Huang¹  Huali Jiang¹  Yunhong Tian¹  Jie Lin¹  Tao Xie²  Anan Xu³  Yawei Yuan³  Baiyao Wang³  Jian Zhang³  Jieling Zheng³  Rong Li⁴ 

[1] Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou, China;Department of Cardiovascularology, the Affiliated Donghua Hospital of Sun Yat-sen University, Dongguan, China;;Department of Radiation Oncology, Affiliated Cancer Hospital &Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China;

关键词: transcriptome sequencing;    cisplatin;    chemoresistance;    nasopharyngeal carcinoma;    differentially expressed gene;    alternative splicing;   

DOI  :  10.3389/fgene.2020.00052

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown