Ge Weiwei, Shi Chao, Ge Chun, Zhang Siyun, Chen Shuhua, Qian Jinfeng
Department of Pathology, Rudong County Hospital of Traditional Chinese Medicine, Rudong, China.
Department of Pathology, Nantong First People's Hospital, No. 666, Shengli Road, Guanyinshan Street, Nantong, 226001, China.
J Mol Histol. 2025 Jul 15;56(4):226. doi: 10.1007/s10735-025-10468-6.
Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer that poses a serious threat to women's health. The aldo-keto reductase type 1 C (AKR1C) family serves as a crucial ferroptosis defense system, catalyzing the conversion of aldehydes and ketones into their corresponding alcohols. SRY-Box4 (SOX4), a transcription factor of the SOX (sry-related HMG-box) family, is important in regulating tumor progression. This study aims to investigate the mechanism through which AKR1C1 mediates the growth, invasion, and ferroptosis of triple-negative breast cancer cells. SRPX2 was highly expressed in TNBC tissues and cells and was detrimental to patient prognosis. SRPX2 knockdown inhibited TNBC cell viability, invasion, and Stemness of tumor while promoting TNBC cell apoptosis and ferroptosis. SOX4 could bind to SRPX2 and was highly expressed in TNBC tissues and cells, down-regulation of SOX4 could inhibit the expression of SRPX2. Silencing SRPX2 inhibited the expression of AKR1C1. Up-regulating AKR1C1 reversed the inhibitory effect of SRPX2 knockdown on cell viability, invasion, and sphere formation abilities, and also reversed the promotive effect on apoptosis in TNBC cells. In vivo, SRPX2 knockdown suppressed tumor growth and expression of Ki67 and AKR1C1 via down-regulated AKR1C1. SOX4 facilitates triple-negative breast cancer progression via promoting SRPX2 transcription to regulate AKR1C. This study is expected to explore potential therapeutic targets and strategies for the treatment of TNBC.
三阴性乳腺癌（TNBC）是乳腺癌的一种特殊亚型，对女性健康构成严重威胁。1C型醛酮还原酶（AKR1C）家族作为一种关键的铁死亡防御系统，催化醛和酮转化为相应的醇。SRY-Box4（SOX4）是SOX（sry相关HMG盒）家族的转录因子，在调节肿瘤进展中起重要作用。本研究旨在探讨AKR1C1介导三阴性乳腺癌细胞生长、侵袭和铁死亡的机制。SRPX2在TNBC组织和细胞中高表达，对患者预后不利。敲低SRPX2可抑制TNBC细胞活力、侵袭和肿瘤干性，同时促进TNBC细胞凋亡和铁死亡。SOX4可与SRPX2结合，在TNBC组织和细胞中高表达，下调SOX4可抑制SRPX2的表达。沉默SRPX2可抑制AKR1C1的表达。上调AKR1C1可逆转敲低SRPX2对细胞活力、侵袭和球形成能力的抑制作用，也可逆转对TNBC细胞凋亡的促进作用。在体内，敲低SRPX2通过下调AKR1C1抑制肿瘤生长以及Ki67和AKR1C1的表达。SOX4通过促进SRPX2转录来调节AKR1C，从而促进三阴性乳腺癌进展。本研究有望探索治疗TNBC的潜在治疗靶点和策略。
