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The Role of CPT2 in Head and Neck Squamous Cell Carcinoma

  • Author(s): Jin, Zhenning
  • Advisor(s): Hu, Shen
  • et al.
No data is associated with this publication.
Abstract

Background: The initiation and development of head and neck squamous carcinoma (HNSCC) is a complicated and multistep process with unclear mechanisms, involving both genetic alternations and epigenetic modifications. CPT2 was found to function as a potential tumor suppressor in hepatocellular carcinoma and its high expression was correlated with better prognosis in colorectal cancer. However, the role of CPT2 in the development of HNSCC remains unclear.

Methods: Data from the Gene Expression Omnibu (GEO) and The Cancer Genome Atlas (TCGA) databases were utilized to analyze the CPT2 gene expression in HNSCC. TCGA-HNSC RNASeq V2 datasets of cancer patients were obtained to investigate the association between CPT2 expression and HNSCC overall survival rate. MTT, migration, Matrigel invasion, and colony-forming assays were performed to evaluate the effect of CPT2 downregulation or upregulation in SCC1 and SCC23 head and neck cancer cells. RNA-sequencing was also performed to analyze the gene expression alterations following CPT2 downregulation. Meanwhile, we also used c-Myc inhibitor to test c-Myc function on CPT2 expression.

Results: Based on the data from the GEO and TCGA databases, the expression level of CPT2 was significantly downregulated in HNSCC tumor tissues, in comparison with the normal controls. After analyzing the datasets of TCGA-HNSC, we found that the patients with high CPT2 expression had better overall survival rate than those with low CPT2 expression. On one hand, knockdown of CPT2 significantly promoted the proliferation, migration, and invasion capability of SCC1 and SCC23 cells. On the other hand, overexpression of CPT2 in HNSCC cells significantly impaired the cell proliferation, migration, and invasion ability in HNSCC cells. RNA-Seq analysis following CPT2 knockdown in SCC23 cells revealed that lysosome, focal adhesion, ECM-receptor interaction, MAPK, ErbB, RIG-I-like receptor, and Toll-like receptor signaling pathways were upregulated after CPT2 suppression. Meanwhile, oxidative phosphorylation, citrate cycle (TCA cycle), RNA degradation, and propanoate metabolism were downregulated following CPT2 downregulation in HNSCC cells. Meanwhile, c-Myc suppressed CPT2 expression on HNSCC cells.

Conclusion: Our study revealed that CPT2 expression was lowered in HNSCC tumor tissues versus normal tissues. Moreover, knockdown of CPT2 enhanced the tumor cell proliferation, migration, and invasion ability, and vice versa. Our findings indicate that CPT2 may function as a tumor suppressor in HNSCC. Moreover, c-Myc suppressed CPT2 expression in SCC1 and SCC23 cells, which could be a potential upstream target. Further studies are warranted to investigate the molecular mechanisms of CPT2 in HNSCC.

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This item is under embargo until June 12, 2021.