HSH2D Promotes the Progression and Chemoresistance of CRC by Regulating the YAP1

Background: Colorectal cancer (CRC) stands out as one of the most widespread and life -threatening malignancies globally. In recent years, significant attention has been directed towards the Yes -associated protein 1 (YAP1), identified as the central effector molecule in the Hippo signaling pathway, highlighting its crucial involvement in CRC development. Nevertheless, the role of hematopoietic SH2 domain -containing (HSH2D) in CRC, and its impact on tumor progression and resistance to chemotherapy by modulating YAP1, remains unclear. Therefore, this study aims to explore the role of HSH2D in CRC and assess its potential therapeutic significance. Methods: The study included the analysis of HSH2D expression levels in CRC tissues and cells by immunohistochemistry and western blot techniques. The influence of HSH2D on CRC cell proliferation and migration was examined using RNA interference and overexpression systems. The regulatory impact of HSH2D on YAP1 expression was assessed through real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and immunoblotting. In vitro cell experiments were conducted to unravel the mechanism by which HSH2D promotes CRC progression through YAP1. Lastly, the study investigated the role of HSH2D in modulating the sensitivity of CRC cells to cisplatin by chemosensitivity experiments. Results: The experimental findings demonstrated a notable elevation in HSH2D expression within both CRC tissues and cells. Overexpression of HSH2D was found to enhance the proliferation and migration capabilities of CRC cells, whereas silencing HSH2D had the opposite effect. Subsequent investigations unveiled that HSH2D upregulated YAP1 expression, and the tumorpromoting influence of HSH2D was, in part, dependent on YAP1. Furthermore, heightened HSH2D expression correlated with increased resistance of CRC cells to cisplatin. Conclusion: This study marks the initial identification of HSH2D upregulation in CRC and its role in advancing the progression and chemoresistance of CRC by modulating YAP1. HSH2D emerges as a promising novel target for CRC treatment, suggesting a potential therapeutic strategy. Future research should delve deeper into the specific interaction mechanisms between HSH2D and YAP1, aiming to effectively target this pathway for enhanced CRC treatment.