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

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.

A 3D Collagen-Based Bioprinted Model to Study Osteosarcoma Invasiveness and Drug Response

“…In keeping with previous evidence [ 24 ], the gene expression of MMP-1 (also named collagenase-1) was strongly increased in the chemoresistant cells compared to parental cells, either in standard 2D or 3D conditions ( Figure 5 a). In addition, U-2OS/CDDP 1 μg cells also expressed a higher level of MMP-9 (also named gelatinase B) in 3D, in line with the presence of more abundant lacunae and cell infiltration ( Figure 4 ).…”

Bioinformatic Analysis Linking Genomic Defects to Chemosensitivity and Mechanism of Action

“…Rapamycin significantly enhanced the expression of interstitial collagenase ( MMP1 ) at the protein and mRNA levels [31]. An assessment of upregulated expression levels in serous ovarian cancer cells by Zhang et al [32] find matrix metalloproteinase 1 ( MMP1 ) to be among the most upregulated mRNAs in the chemoresistant cell lines. Given that MMP1 is the most frequent defective gene associated with MOA:PK (cf.…”

Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action

“…Rapamycin significantly enhanced the expression of interstitial collagenase (MMP1) at the protein and mRNA levels [36]. An assessment of upregulated expression levels in serous ovarian cancer cell lines by Zhang et al [37] find matrix metalloproteinase 1 (MMP1) to be among the most upregulated mRNAs in the chemoresistant cell lines. Given that MMP1 is the most frequent defective gene associated with MOA:PK (cf.…”