Overexpression of microRNA-367 inhibits angiogenesis in ovarian cancer by downregulating the expression of LPA1
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PRIMARY RESEARCH
Cancer Cell International Open Access
Overexpression of microRNA‑367 inhibits angiogenesis in ovarian cancer by downregulating the expression of LPA1 Qingling Zheng1, Xin Dai2, Wei Fang3, Yan Zheng3, Jin Zhang2, Yanxiang Liu2 and Donghua Gu2*
Abstract Background: Compelling evidences reported the role of microRNAs (miRNAs) in ovarian cancer. However, little was known regarding the molecular mechanism of miR-367 in ovarian cancer. This study intended to investigate the role and regulatory mechanism of miR-367 in ovarian cancer involving lysophosphatidic acid receptor-1 (LPA1). Methods: Potentially regulatory miRNAs in ovarian cancer were obtained from bioinformatics analysis. RT-qPCR was used to detect miR-367 expression in both ovarian cancer tissues and relevant adjacent normal tissues. Relationship between miR-367 and LPA1 was predicted by miRNA database and further verified using dual luciferase reporter gene assay and RIP. EdU and Transwell assay were used to measure the proliferation and invasion ability of cells. Moreover, tube formation and chick chorioallantois membrane (CAM) assay were performed to determine angiogenesis of human umbilical vein endothelial cells (HUVECs). Finally, the roles of LPA1 in tumor growth was also studied using nude mice xenograft assay. Results: High expression of LPA1 and low expression of miR-367 were observed in ovarian cancer tissues and cells. Overexpressed miR-367 downregulated LPA1 expression to inhibit proliferation, invasion, and angiogenesis of cancer cells. Low expression of LPA1 suppressed tumor formation and repressed angiogenesis in ovarian in vivo. Conclusion: All in all, overexpression of miR-367 downregulated LPA1 expression to inhibit ovarian cancer progression, which provided a target for the cancer treatment. Keywords: Ovarian cancer, microRNA-367, Lysophosphatidic acid receptor-1, Proliferation, Invasion, Angiogenesis Background Ovarian cancer ranks 7th among cancers in women and 8th cause of cancer death [1]. The progression of ovarian cancer requires the co-evolution of neoplastic cells as well as the adjacent microenvironment [2]. It was reported that the main challenge of ovarian cancer treatment was that most patients have advanced disease at the time of diagnosis [3]. Angiogenesis is a complicated *Correspondence: [email protected] 2 Department of Pathology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, No. 1, Lijiang Road, Huqiu District, Suzhou 215153, Jiangsu, People’s Republic of China Full list of author information is available at the end of the article
process which greatly affects growth, tissue and organ regeneration, and many pathological conditions [4]. Currently, it is reported that angiogenesis is a multi-step process which needs highly modulated endothelial cell behavior [5]. Angiogenesis was reported to be a crucial marker for ovarian cancer development [6]. Thus, it is urgent to develop new strategy for diagnosing ovarian cancer. MicroRNAs (miRNAs) are a variety
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