CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma.
CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma.
复制标题
CLEC3B 在透明细胞肾细胞癌中下调并抑制增殖
DOI：
10.3892/or.2018.6590
复制
发表时间：
2018-10
期刊：
影响因子：
4.2
通讯作者：
An G
中科院分区：
文献类型：
--
作者：
Liu J;Liu Z;Liu Q;Li L;Fan X;Wen T;An G
c型凝集素结构域家族3成员B （CLEC3B）在各种癌症类型患者血清或肿瘤组织中的失调已有报道。然而，cle3b在透明细胞肾细胞癌（ccRCC）中的表达和功能尚不清楚。为了研究cle3b在ccRCC中的功能，我们利用Cancer Genome Atlas （TCGA）和Gene Expression Omnibus （GEO）数据库从转录水平检测cle3b的表达，结果表明，与正常组织相比，ccRCC中cle3b mRNA的表达水平显著下调（在TCGA和GEO数据库中分别P<0.0001和P=0.0392）。在78.9%的ccrcc中，免疫组化进一步证实了cle3b在蛋白水平的下调。为了研究ccRCC中CLEC3B下调的潜在遗传机制，通过对TCGA项目的拷贝数变异数据进行拷贝数分析，发现高达88.1%的ccRCC患者普遍存在CLEC3B拷贝数缺失。cle3b基因缺失伴随着众所周知的von Hippel-Lindau抑癌基因缺失，这是ccRCC癌变过程中的一个特征性致癌事件。在TCGA队列中，cle3b的下调与肿瘤进展相关，并预测不良预后。实时细胞分析系统技术显示，cle3b在体外抑制ccRCC细胞株的增殖，有丝分裂原激活的蛋白激酶途径可能参与了这一过程。在两个大型ccRCC队列中，CLEC3B显示出与增殖抑制剂显著正相关，但与增殖诱导剂和标记物呈负相关，这表明CLEC3B能够识别增殖能力较低的ccRCC。综上所述，本研究结果表明，CLEC3B是ccRCC治疗干预的一个有希望的靶点。
Dysregulation of C-Type Lectin Domain Family 3 Member B (CLEC3B) in serum or tumor tissues has been reported in patients with various cancer types. However, the expression and function of CLEC3B in clear cell renal cell carcinoma (ccRCC) remain unknown. To examine the function of CLEC3B in ccRCC, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were examined to determine the expression of CLEC3B at the transcriptional level and it was demonstrated that CLEC3B mRNA was significantly downregulated in ccRCC compared with normal tissues (P<0.0001 and P=0.0392 in TCGA and GEO databases, respectively). The downregulation of CLEC3B was further validated at the protein level in 78.9% of ccRCCs by immunohistochemistry. To investigate the potential genetic mechanism for CLEC3B downregulation in ccRCC, copy number analysis was performed by profiling the copy number variation data from the TCGA project and it was revealed that the copy number loss of CLEC3B was prevalent in up to 88.1% of patients with ccRCC. CLEC3B genetic deletion was coupled with the well-known genetic loss of the von Hippel-Lindau tumor suppressor, which is a characteristic oncogenic event during ccRCC carcinogenesis. The downregulation of CLEC3B was associated with tumor progression and predicted unfavorable prognostic outcomes in the TCGA cohort. Real-time cell analyzer system technology revealed that CLEC3B inhibited the proliferation of ccRCC cell lines in vitro and that the mitogen-activated protein kinase pathway may contribute to this process. CLEC3B demonstrated substantial positive associations with proliferation inhibitors, but inverse associations with proliferation inducers and markers in two large ccRCC cohorts, suggesting that CLEC3B was able to identify ccRCCs with a lower proliferation capacity. In conclusion, the results of the present study propose that CLEC3B is a promising target for therapeutic intervention in ccRCC.
登录
查看更多内容
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
DOI：
10.1002/anie.201603928
发表时间：
2016-09-12
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Bamborough P;Chung CW;Demont EH;Furze RC;Bannister AJ;Che KH;Diallo H;Douault C;Grandi P;Kouzarides T;Michon AM;Mitchell DJ;Prinjha RK;Rau C;Robson S;Sheppard RJ;Upton R;Watson RJ
通讯作者：
Watson RJ
影响因子：
11.2
作者：
Guo, Yi;Me, Jun;Hoang, Bang H.
通讯作者：
Hoang, Bang H.
DOI：
10.4103/0970-1591.57906
发表时间：
2009-10
期刊：
Indian journal of urology : IJU : journal of the Urological Society of India
影响因子：
--
作者：
Lam JS;Klatte T;Breda A
通讯作者：
Breda A
影响因子：
11.5
作者：
Kaelin, WG
通讯作者：
Kaelin, WG