BACKGROUND Downregulation of microRNA-338-3p (miR-338-3p) was detected in many malignant tumors, which indicated miR-338-3p might serve as a role of antioncogene in those cancers. The present study aimed to explore the roles of miR-338-3p in the growth and metastasis of ovarian cancer cells and elaborate the underlying possible molecular mechanism. METHODS Multiply biomedical databases query and KEGG pathway enrichment assay were used to infilter possible target genes and downstream pathways regulated by miR-338-3p. Overexpression miR-338-3p lentiviral vectors were transfected into ovarian cancer OVCAR-3 and OVCAR-8 cells, cell proliferation, migration and invasion were analyzed by MTT, colony formation, transwell, Matrigel assay and xenograft mouse model. One 3'-untranslated regions (UTRs) binding target gene of miR-338-3p, MACC1 (MET transcriptional regulator MACC1), and its regulated gene MET and downstream signaling pathway activities were examined by western blot. RESULTS Biomedical databases query indicated that miR-338-3p could target MACC1 gene and regulate Met, downstream Wnt/Catenin beta and MEK/ERK pathways. Rescue of miR-338-3p could inhibit the proliferation, migration and invasion of ovarian cancer cells, and suppress the growth and metastasis of xenograft tumor. Restoration of miR-338-3p could attenuate MACC1 and Met overexpression induced growth, epithelial to mesenchymal transition (EMT) and activities of Wnt/Catenin beta and MEK/ERK signaling in vitro and in vivo. CONCLUSIONS The present data indicated that restoration of miR-338-3p could suppress the growth and metastasis of ovarian cancer cells, which might due to the inhibition of proliferation and EMT induced by MACC1, Met and its downstream Wnt/Catenin beta and MEK/ERK signaling pathways.

中文翻译：

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MicroRNA-338-3p 抑制卵巢癌细胞生长和转移：Wnt/catenin beta 和 MEK/ERK 信号通路的影响。


背景 在许多恶性肿瘤中检测到 microRNA-338-3p (miR-338-3p) 的下调，这表明 miR-338-3p 可能在这些癌症中发挥抑癌基因的作用。本研究旨在探讨miR-338-3p在卵巢癌细胞生长和转移中的作用，并阐述其可能的分子机制。方法采用多重生物医学数据库查询和KEGG通路富集分析筛选miR-338-3p可能调控的靶基因及下游通路。将过表达miR-338-3p慢病毒载体转染卵巢癌OVCAR-3和OVCAR-8细胞，通过MTT、集落形成、Transwell、Matrigel实验和异种移植小鼠模型分析细胞增殖、迁移和侵袭。通过western blot检测miR-338-3p的1个3'-非翻译区（UTR）结合靶基因MACC1（MET转录调节因子MACC1）及其调控基因MET和下游信号通路活性。结果生物医学数据库查询表明miR-338-3p可以靶向MACC1基因并调节Met、下游Wnt/Catenin beta和MEK/ERK通路。拯救miR-338-3p可以抑制卵巢癌细胞的增殖、迁移和侵袭，并抑制异种移植肿瘤的生长和转移。恢复 miR-338-3p 可以减弱 MACC1 和 Met 过表达诱导的生长、上皮间质转化 (EMT) 以及体外和体内 Wnt/Catenin beta 和 MEK/ERK 信号传导的活性。结论 目前的数据表明，恢复miR-338-3p可以抑制卵巢癌细胞的生长和转移，这可能是由于抑制MACC1、Met及其下游Wnt/Catenin beta和MEK/ERK诱导的增殖和EMT所致信号通路。