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[Exploring the Mechanism of Paclitaxel Inhibiting T-cell Lymphoma based on High-throughput Sequencing and Public
Si-Zhu Li1, Yi-Bin Yao1, Zhong-Yuan Tang1
1Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
Objective:
To analyze gene expression profile of T cell lymphoma Jurkat cell line treated with paclitaxel by computational biology based on next generation sequencing and to explore the possible molecular mechanism of paclitaxel resistance to T cell lymphoma at gene level.
Methods:
IC50 of paclitaxel on Jurkat cell line was determined by CCK-8 assay. Gene expression profile of Jurkat cells treated with paclitaxel was acquired by next generation sequencing technology. Gene microarray data related to human T cell lymphoma were screened from Gene Expression Omnibus (GEO) database (including 720 cases of T cell lymphoma and 153 cases of normal tissues). Combined with the sequencing data, differential expression genes (DEGs) were intersected and screened. DAVID database was used for enrichment analysis of GO function and KEGG pathway to determine and visualize functional entries of DEGs, and protein-protein interactions network of DEGs was drawn. The levels of gene expression were detected and verified by RT-qPCR.
Results:
CCK-8 results showed that the proliferation of Jurkat cells was inhibited by paclitaxel depended on the concentration apparently. Treated by paclitaxel for 48 h, P<0.05 and |log2(FC)|≥1 were used as filter criteria on the results of RNA Sequencing (RNA-Seq) and GeoChip, 351 DEGs were found from Jurkat cells, including 323 up-regulated genes and 28 down-regulated genes. The GO functional annotation and KEGG pathway enrichment analysis showed that the role of paclitaxel was mainly concentrated in protein heterodimerization activity, nucleosome assembly and transcriptional dysregulation in cancer, etc. The results of RT-qPCR were consistent with those of the sequencing analysis, which verified the reliability of this sequencing.
Conclusion:
Paclitaxel can affect the proliferation and apoptosis of T-cell lymphoma by up-regulating JUN gene, orphan nuclear receptor NR4A family genes and histone family genes.
Insights
Paclitaxel resistance in T-cell lymphoma may involve up-regulation of JUN, NR4A, and histone genes. This study analyzed gene expression in Jurkat cells to uncover molecular mechanisms of paclitaxel resistance.
Area of Science:
- Genomics
- Molecular Biology
- Computational Biology
Background:
- T-cell lymphoma is a significant health concern.
- Paclitaxel is a chemotherapy agent used in cancer treatment.
- Understanding paclitaxel resistance mechanisms is crucial for effective therapy.
Purpose of the Study:
- To analyze the gene expression profile of paclitaxel-treated Jurkat cells using next-generation sequencing.
- To explore the molecular mechanisms of paclitaxel resistance in T-cell lymphoma at the gene level.
Main Methods:
- Cell viability was assessed using CCK-8 assays.
- Gene expression profiling was performed using next-generation sequencing (RNA-Seq).
- Differential gene expression analysis was conducted by integrating RNA-Seq data with public microarray data (GEO database).
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database.
- Protein-protein interaction networks were constructed.
- Gene expression levels were validated using RT-qPCR.
Main Results:
- Paclitaxel inhibited Jurkat cell proliferation in a dose-dependent manner.
- Treatment with paclitaxel identified 351 differentially expressed genes (DEGs) in Jurkat cells, with 323 up-regulated and 28 down-regulated.
- Enrichment analysis indicated that paclitaxel's effects were associated with protein heterodimerization activity, nucleosome assembly, and transcriptional dysregulation in cancer.
- RT-qPCR results confirmed the reliability of the sequencing data.
Conclusions:
- Paclitaxel influences T-cell lymphoma proliferation and apoptosis.
- Up-regulation of JUN, orphan nuclear receptor NR4A family genes, and histone family genes are implicated in paclitaxel's effects.
- These findings provide insights into the molecular basis of paclitaxel resistance in T-cell lymphoma.
