Abstract

The most prevalent subtype of lung cancer is non-small cell lung cancer (NSCLC), which has a low survival rate. Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors being used as first-line treatment for patients with EGFR mutations, drug resistance frequently occurs in most patients. This is due to the involvement of a myriad of genes that help cancer cells survive against EGFR inhibitors, which are still poorly understood. Here, we focus on the molecular profiles that cause drug resistance. Our previous study has shown that the involvement of the arginine metabolic pathway contributes to drug resistance, as revealed by the whole transcriptomics analysis. Our study found that glycine amidinotransferase (GATM) and guanidinoacetate methyltransferase (GAMT) were top-upregulated genes, which catalyze creatine synthesis. GATM is the rate-limiting enzyme in this process. We also discovered that MYC and C15orf48, along with GATM, were upregulated in lung cancer cell lines treated with gefitinib. This suggests that MYC and C15orf48 may regulate GATM to acquire drug resistance. Further analysis showed that GATM promotes drug resistance by upregulating miR-147b, the mature microRNA of its host gene C15orf48. This upregulation generates reactive oxygen species and pseudohypoxia response, promoting drug resistance among lung cancer cell lines. Our study has implications for identifying a potential new target to overcome drug resistance in lung cancer.

Notes

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Graduation Date

2023

Semester

Summer

Advisor

Zhang, Wencai

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Degree Program

Biotechnology

Identifier

CFE0009762; DP0027870

URL

https://purls.library.ucf.edu/go/DP0027870

Language

English

Release Date

August 2028

Length of Campus-only Access

5 years

Access Status

Masters Thesis (Campus-only Access)

Location

College of Medicine

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Restricted to the UCF community until August 2028; it will then be open access.

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