Investigating the influence of taurochenodeoxycholic acid (TCDCA) on pancreatic cancer cell behavior: An RNA sequencing approach

• Published in: Journal of biotechnology 2024-08, Vol.391, p.20-32
• Main Authors: Gál, Eleonóra, Parvaneh, Shahram, Miklós, Vanda, Hegyi, Péter, Kemény, Lajos, Veréb, Zoltán, Venglovecz, Viktória
• Format: Article
• Language: English
• Subjects: adenocarcinoma; angiogenesis; bile; biotechnology; blood serum; Capan-1 cell line; carcinogenesis; cell lines; cell movement; coagulation; gene expression regulation; metastasis; mortality; neoplasm cells; Pancreatic cancer; pancreatic neoplasms; RNA; RNA sequencing; Taurodeoxycholic acid; therapeutics
• ISSN: 0168-1656; 1873-4863; 1873-4863
• DOI: 10.1016/j.jbiotec.2024.05.010

Pancreatic cancer (PC) poses a substantial global health challenge, ranking as the fourth leading cause of cancer-related deaths due to its high mortality rate. Late-stage diagnoses are common due to the absence of specific symptoms. Pancreatic ductal adenocarcinoma (PDAC) accounts for the majority of PC cases. Recent research has suggested a potential link between elevated serum levels of bile acids (BAs) and tumorigenesis of PDAC. This study aims to understand how taurochenodeoxycholic acid (TCDCA), a secondary BA, influences PDAC using RNA sequencing techniques on the Capan-1 cell line. We identified 2,950 differentially expressed genes (DEGs) following TCDCA treatment, with 1,597 upregulated and 1,353 downregulated genes. These DEGs were associated with critical PDAC pathways, including coagulation, angiogenesis, cell migration, and signaling regulation. Furthermore, we reviewed relevant literature highlighting genes like DKK-1, KRT80, UPLA, and SerpinB2, known for their roles in PDAC tumorigenesis and metastasis. Our study sheds light on the complex relationship between BAs and PDAC, offering insights into potential diagnostic markers and therapeutic targets. Further research is needed to unravel these findings' precise mechanisms and clinical implications, potentially improving PDAC diagnosis and treatment. •High Mortality and Late Diagnosis: Pancreatic cancer (PC) is a major global health concern, ranking as the fourth leading cause of cancer-related deaths, primarily due to its high mortality rate and the tendency for late-stage diagnoses.•Bile Acids and Tumorigenesis: Recent studies, including ours, have shown a promising link between elevated serum bile acids (BAs) and the initiation of Pancreatic Ductal Adenocarcinoma (PDAC), the most common form of PC.•Impact of TCDCA: Our research focused on taurochenodeoxycholic acid (TCDCA), a secondary bile acid, and its effects on PDAC using RNA sequencing of the Capan-1 cell line. The sequencing revealed 2,950 differentially expressed genes (DEGs) due to TCDCA exposure.•Key Pathways and Genes: The DEGs identified are connected to critical PDAC pathways such as coagulation, angiogenesis, cell migration, and signaling regulation. Key genes like DKK-1, KRT80, UPLA, and SerpinB2, known for their roles in tumorigenesis and metastasis, were highlighted.•Future Research Directions: While our study provides significant insights into the molecular changes induced by TCDCA, it underscores the necessity for further