Posters

Presenting Author Academic/Professional Position

Salique Hassan Shaham

Academic Level (Author 1)

Post-doc

Discipline/Specialty (Author 1)

Cancer and Immunology

Academic Level (Author 2)

Undergraduate Student

Discipline/Specialty (Author 2)

Cancer and Immunology

Academic Level (Author 3)

Faculty

Discipline/Specialty (Author 3)

Cancer and Immunology

Discipline Track

Biomedical Science

Abstract Type

Research/Clinical

Abstract

Background: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and the second leading cause of cancer-related deaths in the United States. In 2025, an estimated 154,270 new cases of colon cancer are expected to be diagnosed. CRC is projected to cause approximately 52,900 deaths in the U.S. in 2025, slightly increased from the 52,550 deaths estimated the previous year. Metastatic colorectal cancer (mCRC) continues to have a poor prognosis, with a survival rate of less than 15%. Urothelial cancer-associated 1 (UCA1), a long noncoding RNA (lncRNA), is known to be dysregulated in CRC and contributes to tumor progression. Compared to the isogenic oncogenic SW480 cell line, we found that UCA1 is significantly overexpressed in the metastatic colon cancer cell line SW620. This overexpression correlates with the downregulation of mitochondrial pyruvate carrier 1 (MPC1), a protein responsible for transporting pyruvate into the mitochondria. Reduced MPC1 expression impairs oxidative phosphorylation and may contribute to the metabolic reprogramming observed in metastatic CRC.

Methods: Migration, invasion, and proliferation assays were performed on colorectal cancer (CRC) cell lines, including parental (SW480, SW620) and genetically modified variants (SW480+Vec, SW480+UCA1, SW620+shCtrl, SW620+shUCA1). Quantitative RT-PCR was used to measure the expression levels of UCA1, YAP1, Glut1, Fdft1, and MPC1. Immunofluorescence staining was conducted to analyze the localization of YAP1, Glut1, and MPC1 proteins. Glucose and lactate concentrations were measured to evaluate metabolic changes in CRC cells.

Results: The long noncoding RNA UCA1 showed significantly higher expression in the metastatic colorectal cancer (CRC) cell line SW620 compared to the oncogenic (non-metastatic) SW480 cell line. Along with elevated UCA1 levels, the expression of genes involved in glucose metabolism, such as Glut1, YAP1, and Fdft1, was also markedly higher in SW620 cells than in SW480 cells. At the same time, mitochondrial pyruvate carrier 1 (MPC1) was notably downregulated. To further explore this relationship, UCA1 was overexpressed in SW480 cells. This led to significantly increased expression of Glut1, YAP1, and Fdft1, suggesting that UCA1 regulates glucose metabolism. In line with the Warburg effect, where cancer cells limit mitochondrial pyruvate uptake even in the presence of oxygen, MPC1 expression was significantly reduced in metastatic SW620 cells compared to non-metastatic SW480 cells. Similarly, UCA1-overexpressing SW480 cells also showed a marked downregulation of MPC1, suggesting that UCA1 may directly or indirectly suppress MPC1 expression. Since MPC1 is essential for transporting pyruvate into mitochondria and supporting oxidative phosphorylation, its downregulation disrupts mitochondrial metabolism. This implies that MPC1 plays a key role in the Warburg effect and contributes to the metabolic reprogramming and progression of colorectal cancer.

Presentation Type

Poster

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Long Non-Coding RNA UCA1 Regulates MPC1 Expression to Promote the Warburg Effect and Colorectal Cancer Progression

Background: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and the second leading cause of cancer-related deaths in the United States. In 2025, an estimated 154,270 new cases of colon cancer are expected to be diagnosed. CRC is projected to cause approximately 52,900 deaths in the U.S. in 2025, slightly increased from the 52,550 deaths estimated the previous year. Metastatic colorectal cancer (mCRC) continues to have a poor prognosis, with a survival rate of less than 15%. Urothelial cancer-associated 1 (UCA1), a long noncoding RNA (lncRNA), is known to be dysregulated in CRC and contributes to tumor progression. Compared to the isogenic oncogenic SW480 cell line, we found that UCA1 is significantly overexpressed in the metastatic colon cancer cell line SW620. This overexpression correlates with the downregulation of mitochondrial pyruvate carrier 1 (MPC1), a protein responsible for transporting pyruvate into the mitochondria. Reduced MPC1 expression impairs oxidative phosphorylation and may contribute to the metabolic reprogramming observed in metastatic CRC.

Methods: Migration, invasion, and proliferation assays were performed on colorectal cancer (CRC) cell lines, including parental (SW480, SW620) and genetically modified variants (SW480+Vec, SW480+UCA1, SW620+shCtrl, SW620+shUCA1). Quantitative RT-PCR was used to measure the expression levels of UCA1, YAP1, Glut1, Fdft1, and MPC1. Immunofluorescence staining was conducted to analyze the localization of YAP1, Glut1, and MPC1 proteins. Glucose and lactate concentrations were measured to evaluate metabolic changes in CRC cells.

Results: The long noncoding RNA UCA1 showed significantly higher expression in the metastatic colorectal cancer (CRC) cell line SW620 compared to the oncogenic (non-metastatic) SW480 cell line. Along with elevated UCA1 levels, the expression of genes involved in glucose metabolism, such as Glut1, YAP1, and Fdft1, was also markedly higher in SW620 cells than in SW480 cells. At the same time, mitochondrial pyruvate carrier 1 (MPC1) was notably downregulated. To further explore this relationship, UCA1 was overexpressed in SW480 cells. This led to significantly increased expression of Glut1, YAP1, and Fdft1, suggesting that UCA1 regulates glucose metabolism. In line with the Warburg effect, where cancer cells limit mitochondrial pyruvate uptake even in the presence of oxygen, MPC1 expression was significantly reduced in metastatic SW620 cells compared to non-metastatic SW480 cells. Similarly, UCA1-overexpressing SW480 cells also showed a marked downregulation of MPC1, suggesting that UCA1 may directly or indirectly suppress MPC1 expression. Since MPC1 is essential for transporting pyruvate into mitochondria and supporting oxidative phosphorylation, its downregulation disrupts mitochondrial metabolism. This implies that MPC1 plays a key role in the Warburg effect and contributes to the metabolic reprogramming and progression of colorectal cancer.

 

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