Hao Na, Zhou Yudong, Li Yijun, Zhang Huimin, Wang Bin, Liu Xiaona, Ren Yu, He Jianjun, Zhou Can, Tang Xiaojiang
Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Mol Biosci. 2021 Oct 19;8:739978. doi: 10.3389/fmolb.2021.739978. eCollection 2021.
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.
癌症仍然是导致疾病相关死亡的主要元凶之一。缺乏有效的多癌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通用靶点，并进行全面分析以评估它们在肿瘤发生过程中的作用非常重要。OSBPL3蛋白是氧甾醇结合蛋白超家族的一种细胞内脂质受体，它参与肿瘤进展中的一些病理和生理过程。然而，其在癌症中的临床作用和潜在机制仍不清楚。因此，我们旨在使用多个基于网络的公开可用工具，包括癌症基因组图谱（Cancer Genome Atlas）、基因表达综合数据库（Gene Expression Omnibus）、基因型-组织表达数据库（Genotype-Tissue Expression）、cbioportal数据库和人类蛋白质图谱数据库（Human Protein Atlas database），系统地探索OSBPL3在33种肿瘤中的潜在致癌作用。OSBPL3在癌症的主要亚型中高表达，与肿瘤患者的预后明显相关。我们在氧甾醇结构域中观察到X676_splice/V676G改变，并且OSBPL3的频繁突变涉及皮肤黑色素瘤中的细胞存活。我们还首次提出，OSBPL3的表达与9种癌症类型中的肿瘤突变负荷（TMB）相关。此外，在多种肿瘤（如乳腺癌或肺腺癌）中，OSBPL3在普列克底物蛋白同源结构域内的S426、S251和S273位点显示出增强的磷酸化水平。并且OSBPL3的表达与乳腺癌、结肠腺癌和肾透明细胞癌中的活性免疫细胞（CD8 T细胞）和癌症相关成纤维细胞以及30多种肿瘤中的免疫检查点基因相关，但与免疫抑制细胞（髓源性抑制细胞、调节性T细胞）的相关性较弱。此外，蛋白质加工和mRNA代谢信号通路参与了OSBPL3的功能机制。我们的研究首次表明，一种新型因子OSBPL3在各种癌症的公开可用数据库和临床肿瘤样本中，从肿瘤发生的角度发挥重要作用，全面提供了对其生物学功能的见解，可能有助于进一步研究。
