Impact of the SEC62 oncogene on the transcriptome and molecular pathways in head and neck cancer

Introduction SEC62 has been considered as a potential oncogene in various tumor entities for several years and is also overexpressed in approximately 86% of all squamous cell carcinoma patients of the head and neck region (HNSCC). The full molecular function of SEC62 that is essential in post-translational protein translocation of newly synthesized proteins into the ER is not completely understood. Initial studies indicate that SEC62 overexpression is associated with a poor overall survival as well as metastasis stimulation. To investigate the molecular role of SEC62 in detail and to study its impact on the transcriptome of HNSCC cells and their molecular pathways, two stable SEC62-knockout cell lines were generated using CRISPR-Cas9.

Material and Methods Using CRISPR-Cas9, two stable SEC62-ko cell lines were generated originating from FaDu wild-type cells that highly overexpress SEC62. These newly generated ko-cell clones were analyzed and characterized in more detail using RNA-sequencing. The bioinformatics data analysis was performed using Perseus software.

Results A differential gene expression analysis showed that a SEC62-ko significantly regulates a total of 215 genes in both newly generated cell lines. Here, in sum 19 genes were significantly regulated in both ko-cell lines. Four in common regulated genes were significantly down-regulated, 15 genes showed a significant up-regulation.

Discussion Among the shared upregulated genes of both SEC62-ko clones several potential tumor suppressor genes were found. This suggests a link between a SEC62-ko and a resulting reduction in the metastatic and proliferative behaviour of these ko-cells, which makes SEC62 an attractive potential target for new therapeutic strategies.

EKFS, HOMFOR Exzellenz

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Artikel online veröffentlicht:
12. Mai 2023