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CCDC167 作为乳腺癌中细胞周期相关网络的潜在治疗靶点和调节剂。

CCDC167 as a potential therapeutic target and regulator of cell cycle-related networks in breast cancer.

机构信息

Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 70101, Taiwan, Republic of China.

Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, Republic of China.

出版信息

Aging (Albany NY). 2021 Jan 10;13(3):4157-4181. doi: 10.18632/aging.202382.

Abstract

According to cancer statistics reported in 2020, breast cancer constitutes 30% of new cancer cases diagnosed in American women. Histological markers of breast cancer are expressions of the estrogen receptor (ER), the progesterone receptor (PR), and human epidermal growth factor receptor (HER)-2. Up to 80% of breast cancers are grouped as ER-positive, which implies a crucial role for estrogen in breast cancer development. Therefore, identifying potential therapeutic targets and investigating their downstream pathways and networks are extremely important for drug development in these patients. Through high-throughput technology and bioinformatics screening, we revealed that coiled-coil domain-containing protein 167 (CCDC167) was upregulated in different types of tumors; however, the role of CCDC167 in the development of breast cancer still remains unclear. Integrating many kinds of databases including ONCOMINE, MetaCore, IPA, and Kaplan-Meier Plotter, we found that high expression levels of CCDC167 predicted poor prognoses of breast cancer patients. Knockdown of CCDC167 attenuated aggressive breast cancer growth and proliferation. We also demonstrated that treatment with fluorouracil, carboplatin, paclitaxel, and doxorubicin resulted in decreased expression of CCDC167 and suppressed growth of MCF-7 cells. Collectively, these findings suggest that CCDC167 has high potential as a therapeutic target for breast cancer.

摘要

根据 2020 年报告的癌症统计数据,乳腺癌占美国女性新诊断癌症病例的 30%。乳腺癌的组织学标志物是雌激素受体 (ER)、孕激素受体 (PR) 和人表皮生长因子受体 (HER)-2 的表达。高达 80%的乳腺癌被归类为 ER 阳性,这意味着雌激素在乳腺癌发展中起着至关重要的作用。因此,确定潜在的治疗靶点并研究其下游途径和网络对于这些患者的药物开发非常重要。通过高通量技术和生物信息学筛选,我们发现卷曲螺旋结构域蛋白 167 (CCDC167) 在不同类型的肿瘤中上调;然而,CCDC167 在乳腺癌发展中的作用仍不清楚。整合了 ONCOMINE、MetaCore、IPA 和 Kaplan-Meier Plotter 等多种数据库,我们发现 CCDC167 的高表达水平预示着乳腺癌患者预后不良。敲低 CCDC167 可减弱侵袭性乳腺癌的生长和增殖。我们还证明,氟尿嘧啶、卡铂、紫杉醇和多柔比星治疗导致 CCDC167 的表达降低,并抑制 MCF-7 细胞的生长。综上所述,这些发现表明 CCDC167 有很大潜力成为乳腺癌的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ed/7906182/9e888292523a/aging-13-202382-g001.jpg

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