LPA3 isaprecise therapeutic target andpotential biomarker forovarian cancer
LPA3 isaprecise therapeutic target andpotential biomarker forovarian cancer
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LPA3是卵巢癌的精准治疗靶点和潜在生物标志物
DOI：
10.1007/s12032-021-01616-5
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发表时间：
2022
期刊：
影响因子：
3.4
通讯作者：
Hongju Sun1
中科院分区：
文献类型：
--
作者：
Pengfei Zhao;Qingru Yun;· Aodungerile Li;· Rong Li;Yali Yan;Yuewu Wang;Hongju Sun1
目前的研究表明，在卵巢癌患者腹水中观察到LPA水平显著升高。虽然已有研究表明溶血磷脂酸（LPA）与卵巢癌的发生发展有关，但LPA受体（LPARs）和G偶联蛋白亚型介导的LPA作用尚未明确。本研究旨在通过生物信息学分析和生物学实验的方法，阐明LPA在卵巢癌中的作用及其亚型特异性LPARs介导的机制。大数据分析显示，LPA 3是卵巢癌中6种LPARs中唯一差异表达的LPA受体，并在组织芯片免疫组化中得到进一步验证。同时发现LPA 3在卵巢癌组织和卵巢癌细胞中也有高表达。重要的是，LPA显著促进LPA 3过表达的卵巢癌细胞的增殖和迁移，而LPA诱导的作用被LPAR 1/3拮抗剂Ki 16425处理和LPA 3-shRNA转染阻断。体内研究表明，LPA 3过表达细胞来源的肿瘤在裸鼠移植瘤中的转移、肿瘤体积和肿瘤质量明显增加。此外，我们还观察到LPA 3在卵巢癌组织中呈差异性高表达。我们的研究进一步证实了LPA 3/Gi/MAPKs/NF-κB信号参与了LPA诱导的卵巢癌细胞的致癌作用。我们的研究结果表明，LPA 3可能是一个新的精确的治疗靶点和潜在的生物标志物卵巢癌。
Current studies have demonstrated that significant increased LPA levels to be observed in ascites in patients with ovarian cancer. Although several studies have shown that Lysophosphatidic acid (LPA) related to the progression of ovarian cancer, which LPA receptors (LPARs) and G-coupled protein subtypes mediated in LPA actions have not been clearly elucidated. This study aimed to clarify the roles of LPA and it is subtype-specific LPARs mediating mechanisms in ovarian cancer integrated using bioinformatic analysis and biological experimental approaches. The big data analysis shown that LPA3 was the only differentially expressed LPA receptor among the six LPARs in ovarian cancer and further verified in immunohistochemistry of tissue microarrays. Also found that LPA3 was also highly expressed in ovarian cancer tissue and ovarian cancer cells. Importantly, LPA significantly promoted the proliferation and migration of LPA3-overexpressing ovarian cancer cells, while the LPA-induced actions blocked by Ki16425, a LPAR1/3 antagonist treated, and LPA3-shRNA transfected. In vivo study indicated that the LPA3-overexpressing cell-derived tumors metastasis, tumors volume, and tumors mass were apparently increased in xenografted nude mice. In addition, we also observed that LPA3 was differential high expression in ovarian cancer tissue of the patients. Our studies further confirmed the LPA3/Gi/MAPKs/NF-κB signals were involved in LPA-induced oncogenic actions in ovarian cancer cells. Our findings indicated that the LPA3 might be a novel precise therapeutic target and potential biomarker for ovarian cancer.