Wang Danjun, Zhang Jianying, Cai Linhan, Dai Xiaofeng
Beijing Genomics Institution (BGI) College & Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University.
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Front Oncol. 2022 Jul 4;12:895106. doi: 10.3389/fonc.2022.895106. eCollection 2022.
Hepatocellular carcinomas remain as a global health threat given its high mortality rate. We have previously identified the selectivity of cold atmospheric plasma (CAP) against multiple types of malignant tumors and proposed it as a promising onco-therapeutic strategy. Here, we investigated its roles in controlling hepatocellular carcinoma malignancy and one possible driving molecular mechanism. By focusing on post-translational modifications including acetylation, phosphorylation, and ubiquitination, we identified the crosstalk between EGFR acetylation and EGFR(Tyr1068) phosphorylation and their collective roles in determining LC3B ubiquitination and proposed the EGFR/p-JNK/BIRC6/LC3B axis in CAP-triggered autophagy. Our study not only demonstrated the selectivity of CAP against hepatocellular carcinoma malignancy and confirmed its roles as an onco-therapeutic tool but also opened the horizon of translating CAP into clinics toward a broader scope that included human longevity and anti-aging.
鉴于肝细胞癌的高死亡率，它仍然是一个全球性的健康威胁。我们之前已经确定了冷大气等离子体（CAP）对多种类型恶性肿瘤的选择性，并提出它是一种有前景的肿瘤治疗策略。在此，我们研究了其在控制肝细胞癌恶性程度方面的作用以及一种可能的驱动分子机制。通过关注包括乙酰化、磷酸化和泛素化在内的翻译后修饰，我们确定了表皮生长因子受体（EGFR）乙酰化与EGFR（Tyr1068）磷酸化之间的相互作用及其在决定微管相关蛋白1轻链3β（LC3B）泛素化中的共同作用，并提出了CAP触发自噬中的EGFR/磷酸化c-Jun氨基末端激酶（p-JNK）/杆状病毒IAP重复序列6（BIRC6）/LC3B轴。我们的研究不仅证明了CAP对肝细胞癌恶性程度的选择性，并证实了其作为肿瘤治疗工具的作用，还为将CAP应用于临床开辟了更广阔的前景，包括人类长寿和抗衰老。
