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KIAA1549 promotes the development and chemoresistance of colorectal cancer by upregulating ERCC2

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Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Chemotherapy is the mainstay of treatment for patients with CRC in II-IV stages. Resistance to chemotherapy occurs commonly, which results in treatment failure. Therefore, the identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and developing new therapeutic strategies. Herein, we assessed the roles of KIAA1549 in promoting tumor development and chemoresistance in colorectal cancer. As a result, we found that KIAA1549 expression is up-regulation in CRC. Public databases revealed a progressive up-regulation of KIAA1549 expression from adenomas to carcinomas. Functional characterization uncovered that KIAA1549 promotes tumor malignant phenotypes and boosts the chemoresistance of CRC cells in an ERCC2-dependent manner. Inhibition of KIAA1549 and ERCC2 effectively enhanced the sensitivity to chemotherapeutic drugs oxaliplatin and 5-fluorouracil. Our findings suggest that endogenous KIAA1549 might function as a tumor development-promoting role and trigger chemoresistance in colorectal cancer partly by upregulating DNA repair protein ERCC2. Hence, KIAA1549 could be an effective therapeutic target for CRC and inhibition of KIAA1549 combined with chemotherapy might be a potential therapeutic strategy in the future.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all laboratory members of the Department of Pathology of Southern Medical University for their support and comments. The schematic graph is drawn by FigDraw.

Funding

This study was supported by National Natural Science Foundation of China (82273564, 82073342, 82103595); Science and Technology Projects in Guangzhou, China (202206010045, 202201010911); Guangdong Provincial Regional Joint Fund-Youth Fund Project (2020A1515110006); The Foundation of President of Nanfang Hospital (2020C039, 2020C033, 2020C006, 2020B012, 2019B009).

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Author notes

  1. Feng Ye, Yuwen Xie and Mingdao Lin have contributed equally to this work and are co-first authors.

Authors and Affiliations

  1. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Feng Ye, Yuwen Xie, Yang Liu, Yuan Fang, Yaowei Zhang & Yi Ding

  2. Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Mingdao Lin

  3. Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Keli Chen

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Contributions

FY, YX, ML: Conceptualization, Methodology, Software, Writing-Original draft preparation. YL, YF: Writing—Reviewing and Editing. KC: Supervision. YZ, YD: Project administration. All authors discussed the results and approved the manuscript.

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Correspondence to Yi Ding.

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The authors have no relevant financial or non-financial interests to disclose.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Nanfang Hospital of Southern Medical University (NEFC-2022-367).

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Ye, F., Xie, Y., Lin, M. et al. KIAA1549 promotes the development and chemoresistance of colorectal cancer by upregulating ERCC2. Mol Cell Biochem 479, 629–642 (2024). https://doi.org/10.1007/s11010-023-04751-x

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