Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer.
Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer.
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FBXO家族表达与预后相关性的系统分析揭示FBXO1在人类乳腺癌中的意义
DOI：
10.1186/s12935-021-01833-y
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发表时间：
2021-02-23
影响因子：
5.8
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Liu Y;Pan B;Qu W;Cao Y;Li J;Zhao H
背景乳腺癌（Breast cancer，BC）是一种高度异质性的常见肿瘤.努力探索新的分子生物学标记物，作为潜在的疾病指标，这对有效提高BC的预后和个体化治疗至关重要。FBXO蛋白是E3泛素连接酶的核心组分，在多种细胞过程中发挥重要的调节作用。最近，研究表明FBXO在癌症发展中也起着重要作用。然而，这些家庭成员在BC的分子功能尚未完全阐明。MethodsIn this research，我们调查了10 FBXO成员（FBXO 1，2，5，6，16，17，22，28，31和45）的表达数据，生存相关性和突变情况与BC患者从Oncomine，GEPIA，HPA，Kaplan-Meier绘图仪，UALCAN和cBioPortal数据库。通过免疫组化染色证实FBXO 1在不同亚型BC中的高转录水平，并从COSMIC数据库中获得FBXO 1的特异性突变。通过cBioPortal和COXPRESdb工具确定了与FBXO 1相关性最高的前10个基因。此外，从大卫、STRING、UCSC Xena、GEPIA、bc-GenExMiner和Kaplan-Meier Plotter数据库中获得FBXO 1和BC中共表达基因的功能富集分析、PPI网络和生存相关性。将FBXO 1 siRNA转染到MCF-7和MDA-MB-231细胞系中。Western-blot和RT-qPCR检测FBXO 1在BC细胞系中的表达。CCK-8试剂盒和集落形成实验检测细胞增殖。通过伤口愈合和transwell migration assay.ResultsWe发现FBXO 2，FBXO 6，FBXO 16和FBXO 17是BC的潜在有利预后因素。FBXO 1、FBXO 5、FBXO 22、FBXO 28、FBXO 31和FBXO 45可能是BC的独立预后不良因素。与临床病理分期相关。此外，在MCF 7和MDA-MB-231细胞系中敲低FBXO 1导致体外细胞增殖和迁移降低。结论FBXO 1、FBXO 2、FBXO 5、FBXO 6、FBXO 16、FBXO 17、FBXO 22、FBXO 28、FBXO 31和FBXO 45基因是不同分子分型BC患者潜在的临床靶点和预后指标。此外，FBXO 1在乳腺癌中的高表达预示着不良的预后，提示其可能成为乳腺癌患者的一个有吸引力的治疗靶点。
BackgroundBreast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.MethodsIn this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan–Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan–Meier Plotter databases. FBXO1 siRNAs were transfected into MCF-7 and MDA-MB-231 cell lines. Expression of FBXO1 in BC cell lines was detected by western-blot and RT-qPCR. Cell proliferation was detected by using CCK-8 kit and colony formation assay. Cell migration was detected by wound‐healing and transwell migration assay.ResultsWe found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. We identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC.ConclusionThis study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.
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影响因子：
64.8
作者：
Kuchay S;Giorgi C;Simoneschi D;Pagan J;Missiroli S;Saraf A;Florens L;Washburn MP;Collazo-Lorduy A;Castillo-Martin M;Cordon-Cardo C;Sebti SM;Pinton P;Pagano M
通讯作者：
Pagano M
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
11.1
作者：
Cepeda, Diana;Ng, Hwee-Fang;Sharifi, Hamid Reza;Mahmoudi, Salah;Soto Cerrato, Vanessa;Fredlund, Erik;Magnusson, Kristina;Nilsson, Helen;Malyukova, Alena;Rantala, Juha;Klevebring, Daniel;Vinals, Francesc;Bhaskaran, Nimesh;Zakaria, Siti Mariam;Rahmanto, Aldwin Suryo;Grotegut, Stefan;Nielsen, Michael Lund;Szigyarto, Cristina Al-Khalili;Sun, Dahui;Lerner, Mikael;Navani, Sanjay;Widschwendter, Martin;Uhlen, Mathias;Jirstrom, Karin;Ponten, Fredrik;Wohlschlegel, James;Grander, Dan;Spruck, Charles;Larsson, Lars-Gunnar;Sangfelt, Olle
通讯作者：
Sangfelt, Olle
影响因子：
64.5
作者：
Lignitto, Luca;LeBoeuf, Sarah E.;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
11.2
作者：
Kumar, R;Neilsen, PM;Callen, DF
通讯作者：
Callen, DF