The Journal of Practical Medicine ›› 2023, Vol. 39 ›› Issue (9): 1098-1104.doi: 10.3969/j.issn.1006⁃5725.2023.09.006

• Basic Research • Previous Articles     Next Articles

Molecular mechanism of CARM1 regulating ferroptosis in malignant biology of lung cancer cells

LU Tian⁃ long,YANG Qiying,YANG Shiwen,SONG Xiaolong.   

  1. Department of Clinical Laboratory,Qinghai University Affili⁃ ated Hospital,Xining 810000,China

  • Online:2023-05-10 Published:2023-05-10

Abstract:

Objective To explore the molecular mechanism of arginine methyltransferase 1(CARM1)reg⁃ ulating ferroptosis in malignant biology of lung cancer cells. Methods The expression of CARM1 in normal human bronchial epithelial cells(HBE4)and lung cancer lines(A549,H1299,H1640,HCC827)was detected by west⁃ ern blot. CARM1 sequence or Vector and shRNA sequence against CARM1(shCARM1)and Notch homologue 2 (shNotch2)or negative control shRNA(shNC)were transfected into lung cancer cells. Cell proliferation,migration and invasion were measured by CCK ⁃8 test and Transwell test respectively. RIP ⁃PCR and MeRIP ⁃qPCR analysis were used to explore the mechanism of CARM1. Erastin,a classical ferroptosis inducer,was used to treat lung can⁃ cer cells to determine whether CARM1 could affect the sensitivity of cells to ferroptosis. Results Compared with human normal airway epithelial cell HBE4,CARM1 was significantly over⁃expressed in lung cancer lines(A549, H1299,H1640,HCC827)(P < 0.05). Compared with Vector group,the proliferation,migration and invasion ability of A549 cells in CARM1 group was significantly increased(P < 0.001),while that of HCC827 cells in shCARM1 group was significantly lower than that in shNC group(P < 0.001). MeRIP⁃qPCR analysis showed that m6A abundance of Notch2 mRNA increased significantly when CARM1 was overexpressed(P < 0.05). RIP analy⁃ sis showed that CARM1 overexpression significantly promoted the binding between CARM1 and Notch2 mRNA (P < 0.05). Notch2 knockdown weakened the proliferation,invasion and migration of A549 cells up⁃regulated by CARM1(P < 0.001). Conclusion CARM1 is significantly elevated in lung cancer,and plays its carcinogenic role by activating Notch2. In addition,CARM1 can make lung cancer cells insensitive to ferroptosis by stabilizing Notch2.

Key words:

arginine methyltransferase 1, ferroptosis, lung cancer cells, notch homologue 2, ma? lignant biology