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PCDHGB7 通过诱导乳腺癌细胞凋亡抑制 HSPA9 增加顺铂化疗敏感性

PCDHGB7 Increases Chemosensitivity to Carboplatin by Inhibiting HSPA9 via Inducing Apoptosis in Breast Cancer.

机构信息

Department of Pathology, Basic Medical Science College, Harbin Medical University, Harbin, China.

Department of BC Surgery, Harbin Medical University Cancer Hospital, Harbin, China.

出版信息

Dis Markers. 2019 Jul 8;2019:6131548. doi: 10.1155/2019/6131548. eCollection 2019.

Abstract

Breast cancer is one of the most serious cancers worldwide, and chemotherapy resistance frequently drives cancer progression. Triple-negative breast cancer (TNBC) has a high recurrence rate and poor prognosis given its resistance to chemotherapy. In our previous study, we found a remarkable abnormal methylation modification of the PCDHGB7 gene in breast cancer. However, the roles of PCDHGB7 in the progression and treatment of breast cancer are unclear. In this study, we examined the effects of PCDHGB7 on the sensitivity of TNBC cells to carboplatin and investigated the underlying mechanism. By knocking down and overexpressing PCDHGB7 in HS578T and BT549 cells, we confirmed that PCDHGB7 increases TNBC cell chemosensitivity to carboplatin. Mechanistically, we found that PCDHGB7 negatively regulates the expression of HSPA9, uplifting its inhibition on P53 translocation and caspase-3 activation. Thus, we demonstrated that PCDHGB7 increases chemosensitivity of TNBC cells to carboplatin by inhibiting HSPA9 via inducing apoptosis. PCDHGB7 and HSPA9 represent potential therapeutic targets for chemosensitivity in breast cancer.

摘要

乳腺癌是全球最严重的癌症之一,化疗耐药常常导致癌症进展。由于三阴性乳腺癌(TNBC)对化疗的耐药性,其复发率高,预后差。在我们之前的研究中,我们发现乳腺癌中 PCDHGB7 基因存在显著的异常甲基化修饰。然而,PCDHGB7 在乳腺癌的发生发展及治疗中的作用尚不清楚。在这项研究中,我们研究了 PCDHGB7 对 TNBC 细胞对卡铂敏感性的影响,并探讨了其潜在的机制。通过在 HS578T 和 BT549 细胞中敲低和过表达 PCDHGB7,我们证实 PCDHGB7 增加了 TNBC 细胞对卡铂的化疗敏感性。机制上,我们发现 PCDHGB7 通过抑制 HSPA9 诱导细胞凋亡,负调控其对 P53 易位和 caspase-3 激活的抑制作用。因此,我们证明 PCDHGB7 通过诱导细胞凋亡抑制 HSPA9 增加了 TNBC 细胞对卡铂的化疗敏感性。PCDHGB7 和 HSPA9 可能成为乳腺癌化疗敏感性的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ce/6652090/92e892b4c866/DM2019-6131548.001.jpg

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