Jun Yan,Yunfei Zhou,Jianwen Xu,Yihong Dong,Xun Yang,Xinxin Yang,Aodi Wu,Shuyuan Chang,Yumeng Wang,Qingxin Zhang,Tomii Ayaka,Lei Yu,Liuyang Zhao,Hongxue Meng,Dabin Liu
Lactylation is an emerging pathogenesis of hepatocellular carcinoma (HCC). However, the underlying mechanisms and biological significance remain poorly understood. The Carbonic anhydrase III (CA3) gene, previously defined as a binding protein of SQLE and involved in the NAFLD disease, has now been identified as a novel tumor suppressor in HCC. mRNA expression of CA3 is associated with a favorable prognosis and negatively correlated with serum lactate levels, whereas CA3 protein expression does not correlate with patient prognosis or serum lactate levels, suggested there has lactate-related post-translational modification of CA3 in HCC. Overexpression of CA3 induces cell apoptosis, thereby reducing intracellular reactive oxygen stress (ROS) through the inhibition of DUOX2 expression. The decreased lactylation level of CA3 protein at the K36 residues, induced by SQLE, results in the loss of the anti-cancer effect of CA3. Together, this study has demonstrated that CA3 is a novel tumor suppressor in HCC, and delactylation of CA3 represents a newly identified mechanism by which HCC cells evade growth suppressors.
Bangrong Cai,Mengya Liu,Jinxing Li,Dujuan Xu,Jiansheng Li
Chronic obstructive pulmonary disease (COPD) is widely recognized as a global public health problem and the third leading cause of mortality worldwide by 2020. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a dual-specificity protein and lipid phosphatase that plays an important role in COPD. However, the redox regulation of PTEN in the development of COPD was poorly studied. Our results showed that cigarette smoke extract (CSE) could oxidize PTEN in a time-dependent manner in BEAS-2B cells, whereas PTEN oxidation exposed to CSE was delayed compared to that of H 2 O 2. Additionally, we found that ROS derived from DUOX1 and 2 of NADPH oxidases were mainly responsible for oxidative inactivation PTEN, also simultaneously led to Trx-1 inactivation by dimerization . Oxidative mechanism of PTEN exposed to CSE was mediated by forming a disulfide bond between Cys 71 and Cys 124 , similar to H 2 O 2 . Inactivation of PTEN resulted in the increased phosphorylation of Akt. In conclusion, CSE exposure could elevate the intracellular ROS mainly from DUOX1 and 2 to oxidize PTEN and Trx-1 resulting in Akt activation, eventually cause the occurrence of COPD, suggesting that PTEN is a potential target for new therapies in COPD.
危险品化学品经营许可证（带存储）