ORIGINAL RESEARCH article
Front. Med.
Sec. Gastroenterology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1556611
This article is part of the Research TopicDemystifying Fundamental Mechanisms of anticancer drug resistance in Gastrointestinal OncologyView all 4 articles
Hsa_circ_0020095 modulates chemoresistance of CRC in a PDO model
Provisionally accepted
- 1Graduate School of Shandong First Medical University(Shandong Academy of Medical Sciences), Jinan, Shandong, Jinan, Shandong Province, China
- 2Department of Surgical Oncology Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, jinan, China
- 3School of Clinical Medicine, Jining Medical University, Jining, Shandong, China
- 4School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong Province, China
- 5Shandong Provincial Key Laboratory of Precision Oncology,Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences,Jinan, Shandong, jinan, China
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Background: Colorectal cancer (CRC) is the third most common malignant tumor type all over the world with high mortality. Chemoresistance of CRC leads to treatment failure and disease aggravation. We previously identified Hsa_circ_0020095 as a novel oncogene to promote progression and cisplatin-resistance in colon cancers by modulating the miR-487a-3p/SOX9 axis.Methods: Patient-derived organoids (PDOs) were generated from CRC patients and validated by H&E staining, immunohistochemistry (IHC), and whole exome sequencing (WES). Hsa_circ_0020095 was knocked down in PDOs by shRNA and the inhibition of hsa_circ_0020095 was determined using RT-qPCR. The RNA samples analyzed separately,and then pooled together for KEGG and GO analyses.The effects of knocking down hsa_circ_0020095 on drug-resistance of PDOs were examined using CellTiter-Glo®3D Cell viability assay. Finally, the underlying mechanism was explored by transcriptomic sequencing and subsequent bioinformatics analyses.Results: Five organoid lines were successfully established from CRC patients using surgically resected tumor samples. PDOs resembled their parental tumor tissues in morphology, histopathology, and genetic alterations. Silencing of circ_0020095 resulted in remarkable inhibition of hsa_circ_0020095 in PDOs and reversed the resistance of PDOs to 5-FU and oxaliplatin.Mechanistically, hsa_circ_0020095 may function by modulating key pathways and biological functions involved in pathophysiological processes in CRC.Hsa_circ_0020095 modulates chemoresistance of CRC, which could potentially be explored as a therapeutic target for CRC treatment.
Keywords: Hsa_circ_0020095, CRC, Organoids, chemoresistance, POD Abbreviation
Received: 07 Jan 2025; Accepted: 14 Apr 2025.
Copyright: © 2025 Zhao, Gao, Sun, Shan, Li, Li, Zhou and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Changchun Zhou, Shandong Provincial Key Laboratory of Precision Oncology,Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences,Jinan, Shandong, jinan, China
Yanlai Sun, Department of Surgical Oncology Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, jinan, China
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