2023年7月，黑龙江省科学院先进技术研究所;黑龙江省科学院先进技术研究所(Institute of Advanced Technology, Heilongjiang Academy of Sciences；Institute of Advanced Technology, Heilongjiang Academy of Sciences) Guoqing Huang老师研究团队在《Research Square》上发表论文：

“The effect of DDIT3 on luminal A type breast cancer”

“DDIT3对Luminal A型乳腺癌的影响”

Abstract：

Purpose: To analyze the phenotypic changes of breast cancer (BC) cell before and after DDIT3 knockdown/overexpression, and preliminarily explore the regulatory mechanism. Also, to analyze the relationship between DDIT3 and prognosis by combining with bioinformatics methods, which provide a basis for further research on DDIT3 targeted treatment of BC.

Methods: Loss- and gain-of-function studies, DDIT3 in MCF-7 (luminal A), and RNA-seq analysis were employed to investigate the functional impact of DDIT3 on BC cell proliferation and drug resistance. The relationship between DDIT3 and the prognosis of BC patients was systematically assessed using the tissue microarray technique along with qRT-PCR and publicly available data.

Results: Survival analysis showed that patients with lower DDIT3 expression in luminal A type BC or BC patient which were undergoing endocrine therapy had a poorer prognosis, and DDIT3 expression was associated with overall survival (OS) significant. Following the knockdown of DDIT3 in MCF-7 cells, the proliferation rate was significantly increased, and drug resistance ability was just reversed. On the contrary, overexpression of DDIT3 had a relative inhibitory effect on target cell proliferation. Notably, the inhibition of DDIT3 expression upregulated TP63 and downregulated PDGFR, with the results being exactly opposite after the overexpression of DDIT3.

Conclusion: These results have revealed that DDIT3 plays a critical role in luminal A type BC cell proliferation and TAM resistance, and it holds potential prognostic value in BC. Overall, DDIT3 may exert its functions in luminal A type BC by modulating the expression of TP63 and PDGFR.

摘要：

目的:分析乳腺癌(BC)细胞DDIT3敲低/过表达前后的表型变化，并初步探讨其调控机制。结合生物信息学方法分析DDIT3与预后的关系，为进一步研究DDIT3靶向治疗BC提供依据。

方法:通过功能缺失和功能获得研究、MCF-7 (luminal A)中的DDIT3和RNA-seq分析来研究DDIT3对BC细胞增殖和耐药的功能影响。利用组织微阵列技术、qRT-PCR和公开数据系统评估DDIT3与BC患者预后的关系。

结果:生存分析显示，在Luminal A BC或接受内分泌治疗的BC患者中，DDIT3表达较低的患者预后较差，且DDIT3表达与总生存(OS)显著相关。MCF-7细胞中敲低DDIT3后，增殖速率明显提高，耐药能力刚好逆转。相反，过表达DDIT3对靶细胞增殖有相对抑制作用。值得注意的是，抑制DDIT3表达可上调TP63，下调PDGFR，而过表达DDIT3后的结果正好相反。

结论:这些结果揭示了DDIT3在Luminal A BC细胞增殖和TAM耐药中起关键作用，并具有潜在的预后价值。综上所述，dddit3可能通过调节TP63和PDGFR的表达而在luminal A型BC中发挥作用。

该论文中，HEK293T和人乳腺癌(BC)细胞系MCF-7的体外培养是使用Ausbian特级胎牛血清完成的。