Zhang Mingyan, Shi Wenhui, Liu Yanan, Wang Yufeng, Dong Yinying, Yang Chunsheng, Zheng Yawen, Liu Ning, Zheng Yan, Sun Meili
Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong 250013, China.
Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, China.
Clin Transl Radiat Oncol. 2025 Jul 11;54:101016. doi: 10.1016/j.ctro.2025.101016. eCollection 2025 Sep.
Junctional adhesion molecule-like protein (JAML) is highly expressed in cancer tissues of patients with colorectal cancer (CRC) and promotes cancer proliferation. However, the relationship between JAML expression and radiosensitivity of CRC remains unclear.
Stable CRC cell lines with knocked down or overexpressed JAML were used to evaluate the effects of irradiation on cell viability and cell proliferation using Cell Counting Kit-8 (CCK8) and cell clone formation assay, respectively. Cellular immunofluorescence, flow cytometry, and western blotting were used to determine the mechanism. Tumor-bearing nude mouse models were established to verify the relationships between the expression of JAML and the radiosensitivity of CRC.
The results of CCK8 and cell clone formation assay showed that the viability and proliferation of CRC cells with JAML overexpression were significantly inhibited after exposure to irradiation compared with those of CRC cells with low expression of JAML. DNA damage and cell apoptosis were significantly increased in the JAML-overexpression group compared with the JAML-low-expression group after exposure to irradiation. The phosphorylation of the ataxia telangiectasia and Rad3-related protein (ATR)-checkpoint kinase 1 (CHK1)-mediated DNA damage repair pathway was inhibited in the JAML-overexpression group compared with the JAML-low-expression CRC cells after irradiation. Similar results were observed in CRC xenografts .
CRC cells with JAML overexpression are more sensitive to radiotherapy of X-rays because of the decreased phosphorylation of the ATR-CHK1-mediated DNA damage repair pathway. The expression of JAML in CRC cells could be used as a predictive biomarker of radiosensitivity in patients with CRC.
结样粘附分子样蛋白（JAML）在结直肠癌（CRC）患者的癌组织中高表达，并促进肿瘤增殖。然而，JAML表达与CRC放射敏感性之间的关系仍不清楚。
分别使用JAML敲低或过表达的稳定CRC细胞系，通过细胞计数试剂盒-8（CCK8）和细胞克隆形成试验评估辐射对细胞活力和细胞增殖的影响。采用细胞免疫荧光、流式细胞术和蛋白质免疫印迹法确定其机制。建立荷瘤裸鼠模型以验证JAML表达与CRC放射敏感性之间的关系。
CCK8和细胞克隆形成试验结果显示，与JAML低表达的CRC细胞相比，JAML过表达的CRC细胞在接受辐射后活力和增殖受到显著抑制。与JAML低表达组相比，JAML过表达组在接受辐射后DNA损伤和细胞凋亡显著增加。与照射后的JAML低表达CRC细胞相比，JAML过表达组中共济失调毛细血管扩张症和Rad3相关蛋白（ATR）-检查点激酶1（CHK1）介导的DNA损伤修复途径的磷酸化受到抑制。在CRC异种移植瘤中也观察到类似结果。
由于ATR-CHK1介导的DNA损伤修复途径的磷酸化降低，JAML过表达的CRC细胞对X射线放射治疗更敏感。CRC细胞中JAML的表达可作为CRC患者放射敏感性的预测生物标志物。
