lncRNA SNHG4通过EP300-SNHG4-GPX4轴抑制乳腺癌细胞铁死亡

doi:10.11904/j.issn.1002-3070.2023.03.004

Abstract

Abstract: Objective This study aimed to investigate the expression of lncRNA SNHG4 in breast cancer and the mechanism of regulating ferroptosis in breast cancer cells. Methods The tumor tissues of 100 breast cancer patients who underwent surgery in our hospital from January 2017 to December 2018 and the adjacent tissues 3-5 cm away from the tumor edge were collected,and the expression of SNHG4 in breast cancer tissues and paired adjacent tissues was analyzed by RT-PCR.The MDA-MB-468 cell line of breast cancer with SNHG4 knockdown and Hs578T cell line of breast cancer with SNHG4 overexpression were constructed.The CCK-8 assay was used to measure the effect of SNHG4 on the proliferation of breast cancer cells.The changes of iron and ROS were detected by iron content assay kit and MDA assay kit.Western blot was used to detect the expression of GPX4 and EP300 proteins.The correlation between the expression of SNHG4 and EP300,and SNHG4 and GPX4 was analyzed. Results The expression of SNHG4 in breast cancer tissues was higher than that in adjacent tissues(P＜0.01),and it was highly expressed in Basal-Like type and ER(-)breast cancer with strong invasion and migration(P＜0.01).The high expression of SNHG4 was correlated with the short overall survival(OS)and disease-free survival(DFS)of breast cancer patients(P＜0.01).Knockdown of SNHG4 resulted in decreased cell viability(P＜0.01),and this effect could be reversed by inhibitor of ferroptosis.In terms of mechanism,SNHG4 inhibited ferroptosis by up-regulating the expression of GPX4.The upstream of SNHG4 could be positively regulated by histone acetyltransferase,EP300,and EP300 was positively correlated with the expression of SNHG4(P＜0.01). Conclusion SNHG4 is highly expressed in breast cancer and can inhibit ferroptosis of breast cancer cells through EP300-SNHG4-GPX4 axis.

Key words: Breast cancer, Ferroptosis, Glutathione peroxidase-4(GPX4), lncRNA SNHG4, EP300

CLC Number:

R737.9

SUI Shiyao, ZHENG Wei, YANG Zihan, PANG Da. LncRNA SNHG4 inhibits ferroptosis of breast cancer through EP300-SNHG4-GPX4 axis[J]. Journal of Practical Oncology, 2023, 37(3): 215-223.

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URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2023.03.004

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2023/V37/I3/215

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LncRNA SNHG4 inhibits ferroptosis of breast cancer through EP300-SNHG4-GPX4 axis

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