Posters
Presenting Author Academic/Professional Position
Shabnam Malik
Academic Level (Author 1)
Staff
Academic Level (Author 5)
Faculty
Discipline/Specialty (Author 5)
Cancer and Immunology
Discipline Track
Community/Public Health
Abstract Type
Research/Clinical
Abstract
Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer globally and presents a substantial public health concern due to its elevated incidence and mortality rates. A significant challenge in CRC management is the emergence of radio-resistance, which reduces the efficacy of radiotherapy. Thus, it is essential to identify novel molecular mechanisms that contribute to radio-resistance in CRC. Recent studies, including our own, have identified MUC13 as a critical factor in the progression and metastasis of CRC; however, its role in radio-resistance remains inadequately understood. In this study, we investigated the impact of MUC13 expression on radio-resistance in CRC cells.
Methodology: To assess the impact of MUC13 on the radio-resistance of CRC cells, we generated genetically modified cell lines with either MUC13 overexpression (MUC13-OE) or knockdown (MUC13- KO). These cell lines were exposed to X-ray irradiation to evaluate how MUC13 modulation affects critical cellular functions and tumorigenic characteristics, including proliferation, migration, and invasion. Additionally, we measured the expression levels of NRF2 and its nuclear localization following irradiation to elucidate the interplay between the MUC13 and NRF2 signaling pathways. Immunohistochemical analysis of patient-derived tissue samples was performed to determine the expression profiles of MUC13 and NRF2 proteins. Furthermore, bioinformatics analyses were conducted using various public databases to explore the correlation between these two molecules.
Results: Our findings demonstrate that the overexpression of MUC13 (MUC13-OE) in colorectal cancer cells resulted in increased resistance to radiotherapy (X-ray)-induced apoptosis compared to MUC13 knockdown (MUC13-KO) cells. Furthermore, MUC13-OE cells displayed significantly enhanced migratory and invasive abilities following radiation treatment in contrast to MUC13-KO cells. This effect was associated with the upregulation of NRF2 expression and its increased nuclear localization. Notably, a strong correlation between MUC13 and NRF2 expression levels was observed in human CRC tumors, a finding that was corroborated by bioinformatics analyses. Additionally, we identified modulation of other oxidative stress regulators, including HO-1, Keap1, and NQO1, which are essential mediators of cellular responses to oxidative stress. Collectively, these results suggest that MUC13 acts as a key modulator of NRF2 signaling pathway activation, potentially contributing to radio-resistance in CRC patients.
Conclusion: This study is the first to demonstrate the role of MUC13 in radio-resistance in colorectal cancer (CRC) and its relationship with NRF2 expression and localization. Targeting MUC13 with small molecule inhibitors, siRNAs, or miRNAs may enhance the effectiveness of radiotherapy in CRC patients.
Presentation Type
Poster
Recommended Citation
Malik, Shabnam; Sikander, Mohammed; Zubieta, Daniel; Doxtater, Kyle; Tripathi, Manish; Yallapu, Murali; and Chauhan, Subhash, "MUC13 Confers Radio-Resistance in Colorectal Cancer Cells" (2025). Research Colloquium. 73.
https://scholarworks.utrgv.edu/colloquium/2025/posters/73
Included in
MUC13 Confers Radio-Resistance in Colorectal Cancer Cells
Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer globally and presents a substantial public health concern due to its elevated incidence and mortality rates. A significant challenge in CRC management is the emergence of radio-resistance, which reduces the efficacy of radiotherapy. Thus, it is essential to identify novel molecular mechanisms that contribute to radio-resistance in CRC. Recent studies, including our own, have identified MUC13 as a critical factor in the progression and metastasis of CRC; however, its role in radio-resistance remains inadequately understood. In this study, we investigated the impact of MUC13 expression on radio-resistance in CRC cells.
Methodology: To assess the impact of MUC13 on the radio-resistance of CRC cells, we generated genetically modified cell lines with either MUC13 overexpression (MUC13-OE) or knockdown (MUC13- KO). These cell lines were exposed to X-ray irradiation to evaluate how MUC13 modulation affects critical cellular functions and tumorigenic characteristics, including proliferation, migration, and invasion. Additionally, we measured the expression levels of NRF2 and its nuclear localization following irradiation to elucidate the interplay between the MUC13 and NRF2 signaling pathways. Immunohistochemical analysis of patient-derived tissue samples was performed to determine the expression profiles of MUC13 and NRF2 proteins. Furthermore, bioinformatics analyses were conducted using various public databases to explore the correlation between these two molecules.
Results: Our findings demonstrate that the overexpression of MUC13 (MUC13-OE) in colorectal cancer cells resulted in increased resistance to radiotherapy (X-ray)-induced apoptosis compared to MUC13 knockdown (MUC13-KO) cells. Furthermore, MUC13-OE cells displayed significantly enhanced migratory and invasive abilities following radiation treatment in contrast to MUC13-KO cells. This effect was associated with the upregulation of NRF2 expression and its increased nuclear localization. Notably, a strong correlation between MUC13 and NRF2 expression levels was observed in human CRC tumors, a finding that was corroborated by bioinformatics analyses. Additionally, we identified modulation of other oxidative stress regulators, including HO-1, Keap1, and NQO1, which are essential mediators of cellular responses to oxidative stress. Collectively, these results suggest that MUC13 acts as a key modulator of NRF2 signaling pathway activation, potentially contributing to radio-resistance in CRC patients.
Conclusion: This study is the first to demonstrate the role of MUC13 in radio-resistance in colorectal cancer (CRC) and its relationship with NRF2 expression and localization. Targeting MUC13 with small molecule inhibitors, siRNAs, or miRNAs may enhance the effectiveness of radiotherapy in CRC patients.
