Lu Yu-Long, Yang Xin, Liu Ya-Kui
Department of General Surgery, Xiangya Second Hospital, Central South University Changsha, Hunan, PR China.
Department of Thoracic Surgery, Jingmen First People's Hosptial Jingmen, Hubei, PR China.
Int J Clin Exp Pathol. 2019 Jan 1;12(1):142-153. eCollection 2019.
Breast cancer (BC) is one of the most lethal types of cancer throughout the world due its proliferation and invasion. PDZ domain containing ring finger 4 (PDZRN4) belongs to the LNX family, which has E3 ubiquitin ligase activity and is involved in the progression of cancer. However, the role of PDZRN4 in the progression of BC remains unknown. In the present study, the public database Oncomine was used to detect PDZRN4 expression for primary screening. BC tissues and matched normal tissues were collected for detection of expression and cohort analysis. BC cells were used for invasion and proliferation function tests and . The results revealed that both the mRNA and protein levels of PDZRN4 in the BC tissues were markedly reduced compared to normal tissues. The expression of PDZRN4 was significantly correlated with LNM, histological grade and perineural invasion. Prognostic analysis confirmed that PDZRN4 expression is an independent risk factor for overall survival and disease-free survival of patients with BC. The functional experiments demonstrated that knockdown of PDZRN4 significantly improved the invasive and proliferative abilities of BT-20 cells and . Furthermore, overexpression of PDZRN4 markedly inhibited the malignant aspects of MDA-MB-231 cells. Therefore, reduced PDZRN4 correlates with the progression of BC and may act as a novel prognostic marker for patients with BC.
乳腺癌（BC）因其增殖和侵袭性，是全球最致命的癌症类型之一。含PDZ结构域的环指蛋白4（PDZRN4）属于LNX家族，具有E3泛素连接酶活性，并参与癌症进展。然而，PDZRN4在BC进展中的作用尚不清楚。在本研究中，使用公共数据库Oncomine检测PDZRN4表达进行初步筛选。收集BC组织和配对的正常组织用于检测表达和队列分析。使用BC细胞进行侵袭和增殖功能测试。结果显示，与正常组织相比，BC组织中PDZRN4的mRNA和蛋白质水平均显著降低。PDZRN4的表达与淋巴结转移、组织学分级和神经周围浸润显著相关。预后分析证实，PDZRN4表达是BC患者总生存和无病生存的独立危险因素。功能实验表明，敲低PDZRN4显著提高了BT-20细胞的侵袭和增殖能力。此外，PDZRN4的过表达显著抑制了MDA-MB-231细胞的恶性表型。因此，PDZRN4表达降低与BC进展相关，可能作为BC患者的一种新的预后标志物。
