Clinical Value and Potential Mechanisms of Oxysterol-Binding Protein Like 3 (OSBPL3) in Human Tumors.
Clinical Value and Potential Mechanisms of Oxysterol-Binding Protein Like 3 (OSBPL3) in Human Tumors.
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DOI：
10.3389/fmolb.2021.739978
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发表时间：
2021
影响因子：
5
通讯作者：
Tang X
中科院分区：
文献类型：
--
作者：
Hao N;Zhou Y;Li Y;Zhang H;Wang B;Liu X;Ren Y;He J;Zhou C;Tang X
癌症仍然是导致疾病相关死亡的罪魁祸首之一。缺乏有效的多肿瘤治疗靶点，限制了癌症患者生存期的延长。因此，探索新的致癌基因或多功能靶点并进行综合分析以评估其在肿瘤发生过程中的作用是非常重要的。OSBPL3蛋白是氧甾醇结合蛋白超家族的胞内脂质受体，参与肿瘤进展过程中的一些病理生理过程。然而，其在癌症中的临床作用和潜在机制尚不清楚。因此，我们的目标是系统地探索OSBPL3在33种肿瘤中的潜在致癌作用，使用多种基于网络和公开的工具，包括癌症基因组图谱、基因表达Omnibus、基因型-组织表达、cBioPortal和人类蛋白质图谱数据库。OSBPL3在主要癌症亚型中高表达，与肿瘤患者预后明显相关。我们观察到X676_splice/V676G在羟甾醇结构域的改变和OSBPL3的频繁突变与皮肤黑色素瘤的细胞存活有关。我们还首次提出了OSBPL3的表达与9种癌症类型的肿瘤突变负荷（TMB）相关。此外，在多种肿瘤（如乳腺癌或肺腺癌）中，OSBPL3在pleckstrin同源结构域中的S426、S251和S273位点的磷酸化水平增强。OSBPL3表达与乳腺癌、结肠癌、肾透明细胞癌的活性免疫细胞（CD8+ T细胞）和癌相关成纤维细胞相关，与30多种肿瘤的免疫检查点基因相关，但与免疫抑制细胞（骨髓源性抑制细胞、T调节细胞）相关较弱。此外，OSBPL3的功能机制还涉及蛋白加工和mRNA代谢信号通路。我们的研究首先从公开的数据库和各种癌症的临床肿瘤样本的角度证明了一种新的药物OSBPL3在肿瘤发生中起着重要的作用，全面地了解了其生物学功能，可能有助于进一步的研究。
Cancer remains one of the top culprits causing disease-related deaths. A lack of effective multi-cancer therapeutic targets has limited the prolongation of cancer patients’ survival. Therefore, it is important to explore novel oncogenic genes or versatile targets and perform a comprehensive analysis to assess their roles in the process of tumorigenesis. OSBPL3 protein is an intracellular lipid receptor of the oxysterol-binding protein superfamily, which participates in some pathological and physiological processes in tumor progression. However, its clinical roles and potential mechanisms in cancers remain unknown. Thus, we aimed to systematic explore the potential oncogenic roles of OSBPL3 across thirty-three tumors using multiple web-based and publicly available tools, including the Cancer Genome Atlas, Gene Expression Omnibus, Genotype-Tissue Expression, cBioPortal, and Human Protein Atlas database. OSBPL3 is highly expressed in major subtypes of cancers, distinctly associated with the prognosis of tumor patients. We observed X676_splice/V676G alteration in the oxysterol domain and frequent mutations of OSBPL3 involve cell survival in skin cutaneous melanoma. We also first presented that the expression of OSBPL3 was associated with tumor mutational burden (TMB) in nine cancer types. Additionally, OSBPL3 shows an enhanced phosphorylation level at S426, S251, and S273 loci within the pleckstrin homology domain in multiple tumors, such as breast cancer or lung adenocarcinoma. And OSBPL3 expression was associated with active immune cells (CD8+ T cells) and cancer-associated fibroblasts in breast cancer, colon adenocarcinoma, and kidney renal clear cell carcinoma and immune checkpoint genes in more than 30 tumors, but weakly associated with immune suppressive cells (myeloid-derived suppressor cells, T regulatory cells). Moreover, protein processing and mRNA metabolic signaling pathways were involved in the functional mechanisms of OSBPL3. Our study first demonstrated that a novel agent OSBPL3 plays an important role in tumorigenesis from the perspective of publicly available databases and clinical tumor samples in various cancers, which comprehensively provide insights into its biological functions and may be helpful for further investigation.
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影响因子：
3.1
作者：
Collier, FM;Gregorio-King, CC;Kirkland, MA
通讯作者：
Kirkland, MA
DOI：
10.3324/haematol.13186
发表时间：
2008-12-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Lopez-Guerra, Monica;Trigueros-Motos, Laia;Pastor-Anglada, Marqal
通讯作者：
Pastor-Anglada, Marqal
影响因子：
3.7
作者：
Lehto, M;Hynynen, R;Olkkonen, VM
通讯作者：
Olkkonen, VM
影响因子：
15.8
作者：
Lefebvre C;Bachelot T;Filleron T;Pedrero M;Campone M;Soria JC;Massard C;Lévy C;Arnedos M;Lacroix-Triki M;Garrabey J;Boursin Y;Deloger M;Fu Y;Commo F;Scott V;Lacroix L;Dieci MV;Kamal M;Diéras V;Gonçalves A;Ferrerro JM;Romieu G;Vanlemmens L;Mouret Reynier MA;Théry JC;Le Du F;Guiu S;Dalenc F;Clapisson G;Bonnefoi H;Jimenez M;Le Tourneau C;André F
通讯作者：
André F
影响因子：
--
作者：
Li H;Wang X;Fang Y;Huo Z;Lu X;Zhan X;Deng X;Peng C;Shen B
通讯作者：
Shen B