Department of Head and Neck Cancer Center, Chongqing University Cancer Hospital, Chongqing 400030, China.
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China.
Aging (Albany NY). 2022 Sep 5;14(17):7003-7013. doi: 10.18632/aging.204265.
Radiotherapy resistance is the main obstacle in the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). Increasing scientific opinions present that ubiquitin-conjugating enzyme E2C (UBE2C) might be a target gene acting as an oncogene.
TCGA database was used to analyze the expression of UBE2C in HNSCC patients, and the relationship between UBE2C expression and prognosis. Western blot and RT-PCR were used to assess UBE2C expression before and after radiation. Then, cell viability experiment and colony formation were used to evaluate proliferation after 2 Gy radiation. Cell viability experiment, migration, and invasion were evaluated in the condition of UBE2C knock-down. Western blot and RT-PCR were used to assess the expression of apoptosis and ROS relative gene expression. Then, the xenograft model was used to evaluate the efficacy of radiation combined with UBE2C suppression.
The expression of UBE2C was high in tumors of patients with HNSCC and relatives with poor prognoses. Si-UBE2C cells showed proliferation inhibited and apoptosis enhanced after radiation. Furthermore, the mechanism of UBE2C in HNSCC radioresistance was explored. We performed RT-PCR to find the 4-HNE, which increases oxidative-stress-relative apoptosis in Si-UBE2C cells after radiation.
Through the RT-PCR, WB, cell viability experiment, migration, invasion, and experiment, UBE2C was confirmed to downregulate oxidative-stress-relative apoptosis induced by radiation and promote the development of malignant tumor cells.
放射治疗抵抗是有效治疗晚期头颈部鳞状细胞癌（HNSCC）的主要障碍。越来越多的科学观点认为，泛素结合酶 E2C（UBE2C）可能是一种作为癌基因发挥作用的靶基因。
利用 TCGA 数据库分析 HNSCC 患者 UBE2C 的表达情况，以及 UBE2C 表达与预后的关系。采用 Western blot 和 RT-PCR 检测放射前后 UBE2C 的表达。然后，通过细胞活力实验和集落形成实验评估 2Gy 照射后细胞的增殖情况。在 UBE2C 敲低的条件下，通过细胞活力实验、迁移和侵袭实验评估细胞的迁移和侵袭能力。采用 Western blot 和 RT-PCR 检测凋亡和 ROS 相关基因表达。然后，建立异种移植模型评估放射联合 UBE2C 抑制的疗效。
UBE2C 在 HNSCC 患者和亲属的肿瘤中表达较高，且预后较差。Si-UBE2C 细胞在放射后表现出增殖抑制和凋亡增强。此外，还探讨了 UBE2C 在 HNSCC 放射抵抗中的作用机制。我们进行 RT-PCR 发现，4-HNE 在 Si-UBE2C 细胞中增加了放射后氧化应激相关的细胞凋亡。
通过 RT-PCR、WB、细胞活力实验、迁移、侵袭和实验，证实 UBE2C 下调放射诱导的氧化应激相关细胞凋亡，促进恶性肿瘤细胞的发展。
