Role of hsa_Circ_0001821 in Colorectal Cancer Pathogenesis and Response to 5-Fluorouracil through miR-203a-3p/FGF-2 Axis

Authors
Pejman Molaei 1
Ali Mahdavinezhad 1
Rezvan Najafi 1
Mehrdad Hashemi 2
Leili Tapak 3
Saeid Afshar 4
1 Department of molecular medicine, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran
2 Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
3 Modeling of Noncommunicable Diseases Research Center, Institute of Health Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran
4 Department of Biostatistics, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
10.61882/ibj.4942
Abstract
Background: Chemoresistance, the primary cause of disease relapse and treatment failure, poses a significant challenge in the treatment of colorectal cancer (CRC). Understanding the molecular mechanisms that underlie the pathogenesis and chemoresistance of colorectal tumor cells, as well as identifying novel therapeutic strategies, would be crucial. This study aimed to evaluate the role of hsa_Circ_0001821 in response to 5-fluorouracil (5-FU) in CRC, a topic that has not been examined to date.

Methods: The current study investigated the effect of hsa_Circ_0001821 suppression using interfering RNAs on the response of colorectal tumor cells to 5-FU. The expression levels of hsa_Circ_0001821, hsa-miR-203a-3p, BAX, BCL-2, and FGF-2 were determined via quantitative RT-PCR. Cell survival, migration rate, and apoptosis induction of colorectal tumor cells subjected to 5-FU treatment were assessed using the MTT test, scratch assay, and flow cytometry analysis, respectively.

Results: Knockdown of hsa_Circ_0001821 with siRNA increased the expression level of hsa-miR-203a-3p and decreased the expression level of FGF-2. Additionally, the knockdown of hsa_Circ_0001821 enhanced the sensitivity of colorectal tumor cells to 5-FU. This circRNA significantly affected the viability, apoptosis, and migration of tumor cells.

Conclusion: Our study reveals the potential role of hsa_Circ_0001821 in controlling the tumor cell viability and response to 5-FU by targeting the hsa-miR-203a-3p/FGF-2 axis. These findings enhance our understanding of the molecular mechanisms that influence chemotherapy response in CRC, paving the way for the identification of more effective treatments for this disease.
Keywords
Colorectal neoplasm
Circ_0001821
5-Fluorouracil
miR-203a-3p
FGF-2