Natarajan Sathan Raj, Krishnamoorthy Rajapandiyan, Alshuniaber Mohammad A, Alsulami Tawfiq S, Gatasheh Mansour K, Rajagopal Ponnulakshmi, Palanisamy Chella Perumal, Govindan Ramajayam, Veeraraghavan Vishnu Priya, Jayaraman Selvaraj
Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Institute of Medical & Technical Sciences, Saveetha Dental College & Hospitals, Saveetha University, Chennai, 600 077, India.
Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
Sci Rep. 2025 Jul 9;15(1):24674. doi: 10.1038/s41598-025-92436-4.
Colorectal cancer (CRC) poses a formidable challenge to global health, necessitating the quest for novel biomarkers to improve therapeutic strategies. This study explores ABCE1 (ATP-binding cassette subfamily E member 1) as a potential biomarker for CRC and delves into its intricate molecular mechanisms. Through integrated bioinformatic analyses, this study underscores the significant oncogenic role of ABCE1 in CRC, opening new avenues for promising therapeutic interventions. Deletion of ABCE1 reduced cell growth, abrogated aerobic glycolysis, and promoted apoptosis in HT-29 and HCT-116 cells. Further validation through experimentation with irinotecan revealed compelling outcomes, including diminished cell growth, induces G1 phase cell cycle arrest, and promotes apoptosis in HCT-116 and HT-29 colorectal cancer cells. ABCE1 KO with irinotecan combined treatment significantly increased the inhibition of cell proliferation and aerobic glycolysis in CRC cells, accentuating the multifaceted role of ABCE1 in CRC progression. Moreover, this work also demonstrated the complex relationship between ABCE1 and the p53 signalling pathway, which was confirmed in experimental assays. These assays also revealed that deletion of ABCE1 with irinotecan might regulate G1 phase cell cycle arrest, inhibit metabolic regulation, and activate the p53 pathway to induce apoptosis in HCT-116 cells. Molecular docking analyses further supported these findings, revealing the strong binding affinity of irinotecan for targets of the p53 signalling cascade. Collectively, these comprehensive insights support the potential therapeutic efficacy of targeting ABCE1 in CRC treatment strategies. Overall, the findings from this study underscore the importance of ABCE1 as a potential biomarker in CRC and illuminate its complex molecular mechanisms. The demonstrated effectiveness of ABCE1 inhibition, particularly through irinotecan, coupled with its interplay with crucial signalling pathways such as p53, highlights its potential as a promising therapeutic option for colorectal cancer treatment.
结直肠癌（CRC）对全球健康构成了巨大挑战，因此需要寻找新的生物标志物来改进治疗策略。本研究探索ABCE1（ATP结合盒亚家族E成员1）作为CRC的潜在生物标志物，并深入研究其复杂的分子机制。通过综合生物信息学分析，本研究强调了ABCE1在CRC中的重要致癌作用，为有前景的治疗干预开辟了新途径。ABCE1的缺失降低了HT-29和HCT-116细胞的生长，消除了有氧糖酵解，并促进了细胞凋亡。通过伊立替康实验进一步验证得出了令人信服的结果，包括细胞生长减少、诱导HCT-116和HT-29结肠癌细胞的G1期细胞周期停滞以及促进细胞凋亡。ABCE1基因敲除与伊立替康联合治疗显著增强了对CRC细胞增殖和有氧糖酵解的抑制作用，突出了ABCE1在CRC进展中的多方面作用。此外，这项研究还证明了ABCE1与p53信号通路之间的复杂关系，这在实验分析中得到了证实。这些分析还表明，伊立替康联合ABCE1基因敲除可能调节HCT-116细胞的G1期细胞周期停滞、抑制代谢调节并激活p53通路以诱导细胞凋亡。分子对接分析进一步支持了这些发现，揭示了伊立替康对p53信号级联靶点的强结合亲和力。总体而言，这些全面的见解支持了在CRC治疗策略中靶向ABCE1的潜在治疗效果。本研究结果强调了ABCE1作为CRC潜在生物标志物的重要性，并阐明了其复杂的分子机制。ABCE1抑制的有效性，特别是通过伊立替康，以及它与p53等关键信号通路的相互作用，突出了其作为结直肠癌治疗有前景的治疗选择的潜力。
