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富含半胱氨酸的酸性分泌蛋白的综合基因组分析及其在癌症预测中的作用。

Integrative genomic analyses of secreted protein acidic and rich in cysteine and its role in cancer prediction.

作者信息

Wang Bo, Chen Kai, Xu Wenming, Chen Di, Tang Wei, Xia Tian-Song

机构信息

Department of Medical Oncology, Huangpu Division of the First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510700, P.R. China.

Department of Internal Medicine, Huangpu Division of the First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510700, P.R. China.

出版信息

Mol Med Rep. 2014 Sep;10(3):1461-8. doi: 10.3892/mmr.2014.2339. Epub 2014 Jun 17.

Abstract

Secreted protein acidic and rich in cysteine (SPARC), also termed osteonectin or basement‑membrane‑40 (BM‑40), is a matrix‑associated protein that elicits changes in cell shape, inhibits cell‑cycle progression and affects the synthesis of extracellular matrix (ECM). The final mature SPARC protein has 286 amino acids with three distinct domains, including an NH2‑terminal acidic domain (NT), follistatin‑like domain (FS) and C terminus domain (EC). The present study identified SPARC genes from 14 vertebrate genomes and revealed that SPARC existed in all types of vertebrates, including fish, amphibians, birds and mammals. In total, 21 single nucleotide polymorphisms (SNPs) causing missense mutations were identified, which may affect the formation of the truncated form of the SPARC protein. The human SPARC gene was found to be expressed in numerous tissues or organs, including in the bone marrow, whole blood, lymph node, thymus, brain, cerebellum, retina, heart, smooth muscle, skeletal muscle, spinal cord, intestine, colon, adipocyte, kidney, liver, pancreas, thyroid, salivary gland, skin, ovary, uterus, placenta, cervix and prostate. When searched in the PrognoScan database, the human SPARC gene was also found to be expressed in bladder, blood, breast, glioma, esophagus, colorectal, head and neck, ovarian, lung and skin cancer tissues. It was revealed that the association between the expression of SPARC and prognosis varied in different types of cancer, and even in the same cancer from different databases. It implied that the function of SPARC in these tumors may be multidimensional, functioning not just as a tumor suppressor or oncogene.

摘要

富含半胱氨酸的酸性分泌蛋白(SPARC),也称为骨连接蛋白或基底膜40(BM - 40),是一种与基质相关的蛋白质,可引起细胞形态变化、抑制细胞周期进程并影响细胞外基质(ECM)的合成。最终成熟的SPARC蛋白有286个氨基酸,包含三个不同结构域,即氨基末端酸性结构域(NT)、卵泡抑素样结构域(FS)和C末端结构域(EC)。本研究从14种脊椎动物基因组中鉴定出SPARC基因,并揭示SPARC存在于所有类型的脊椎动物中,包括鱼类、两栖类、鸟类和哺乳类。总共鉴定出21个导致错义突变的单核苷酸多态性(SNP),这可能会影响SPARC蛋白截短形式的形成。研究发现人类SPARC基因在众多组织或器官中表达,包括骨髓、全血、淋巴结、胸腺、脑、小脑、视网膜、心脏、平滑肌、骨骼肌、脊髓、肠、结肠、脂肪细胞、肾、肝、胰腺、甲状腺、唾液腺、皮肤、卵巢、子宫、胎盘、宫颈和前列腺。在PrognoScan数据库中搜索时,还发现人类SPARC基因在膀胱癌、血癌、乳腺癌、神经胶质瘤、食管癌、结直肠癌、头颈癌、卵巢癌、肺癌和皮肤癌组织中表达。结果显示,SPARC表达与预后之间的关联在不同类型癌症中有所不同,甚至在来自不同数据库的同一种癌症中也存在差异。这意味着SPARC在这些肿瘤中的功能可能是多维度的,不仅仅作为肿瘤抑制因子或癌基因发挥作用。

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