Date of Award
2025-08-01
Degree Name
Doctor of Philosophy
Department
Biological Sciences
Advisor(s)
Sourav S. Roy
Abstract
Despite advances in screening and treatment, colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the U.S., with notable disparities across racial and ethnic groups. Hispanic populations face a disproportionate burden, underscoring significant differences in incidence and outcomes. This study examines the role of the Stress-Survival Pathway (SSP) in colorectal cancer (CRC), with a focus on addressing health disparities among Hispanic populations. Twenty-eight differentially expressed SSP genes identified from bioinformatic analysis were validated in CRC cell lines and cDNA arrays using qRT-PCR and tissue microarrays by immunohistochemistry. SSP genes were further analyzed in CRC tissues from Hispanic and non-Hispanic White (NHW) individuals, including early-onset and late-stage samples. Among all SSP genes, we selected MCM10 for further investigation due to its limited studies in CRC and consistent overexpression across all experiments, including those involving Hispanic CRC samples, highlighting its potential role in CRC disparities. We hypothesized that MCM10 plays a critical role in CRC pathogenesis and may contribute to the disparities in disease progression observed in Hispanic patients. We performed a series of functional assays, including proliferation, invasion, migration, cell cycle analysis, apoptosis, and reactive oxygen species (ROS) assessment, following the knockdown of MCM10, to investigate its role in CRC progression. The results indicated that silencing MCM10 significantly inhibited cell proliferation, reduced invasive and migratory capabilities, increased apoptotic rates, and altered cell cycle progression while also affecting ROS levels in cancer cells. Additionally, we conducted RNA sequencing and mass spectrometry following MCM10 knockdown, which enabled us to integrate transcriptomic and proteomic analyses, revealing significant changes associated with PPFIA1. These findings suggest that SSP genes, particularly MCM10, play a significant role in CRC progression and may serve as a potential therapeutic target to address ethnic disparities in CRC outcomes.
Language
en
Provenance
Received from ProQuest
Copyright Date
2025-08
File Size
215 p.
File Format
application/pdf
Rights Holder
Urbashi Basnet
Recommended Citation
Basnet, Urbashi, "Stress-Survival Pathway Genes In Colorectal Cancer: Crc Progression And Hispanic Disparities, Highlighting Mcm10 As A Potential Player" (2025). Open Access Theses & Dissertations. 4333.
https://scholarworks.utep.edu/open_etd/4333