LPA3 isaprecise therapeutic target andpotential biomarker forovarian cancer
LPA3 isaprecise therapeutic target andpotential biomarker forovarian cancer
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DOI:
10.1007/s12032-021-01616-5
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发表时间:
2022
期刊:
影响因子:
--
通讯作者:
Alatangaole D
中科院分区:
文献类型:
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作者:
Pengfei Zhao(一作);Qingru Yun;Aodungerile Li;Rong Li;Yali Yan;Yuewue Wang;Hongju Sun;Alatangaole D
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 biologi cal 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 ver ified in immunohistochemistry .of tissue microarrays. Also found that LPA3 was also highly expressed in ovarian cancer tissue and ovarian cancer cells. .Impor tantly, 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 patient s. Our studies further confirmed the LPA3/Gi/MAPKs/NF-κB signals were involved in LPA-induced .oncogenic acti ons in ovarian cancer cells. Our findings indicated that the LPA3 might be a novel precise therapeutic target .and potential biomarker for ovar ian cancer.