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长链非编码 RNA LUCAT1 通过调控 miR-612/HOXA13 通路促进卵巢癌的恶性进展。

Long noncoding RNA LUCAT1 promotes malignancy of ovarian cancer through regulation of miR-612/HOXA13 pathway.

机构信息

Department of Gynaecology, Zhoukou Central Hospital, Zhoukou, 466000, China.

Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

出版信息

Biochem Biophys Res Commun. 2018 Sep 10;503(3):2095-2100. doi: 10.1016/j.bbrc.2018.07.165. Epub 2018 Aug 6.

DOI:10.1016/j.bbrc.2018.07.165
PMID:30107913
Abstract

Emerging evidence shows that long noncoding RNA (lncRNA) is implicated in numerous kinds of malignant cancers, including ovarian cancer. In this study, we focused on the expression and function of long noncoding RNA lung cancer associated transcript 1 (LUCAT1) in ovarian cancer progression. We indicated that LUCAT1 expression was significantly upregulated in ovarian cancer tissues. Moreover, LUCAT1 expression was positively associated with tumor metastasis and clinical stage. Elevated expression of LUCAT1 decreased the survival rate of patients with ovarian cancer. In addition, we revealed that repression of LUCAT1 significantly suppressed the proliferation, migration and invasion, whereas promoted apoptotic rate. Through online predictive tools and functional experiments, we demonstrated that LUCAT1 and HOXA13 were targets of miR-612. We showed that LUCAT1 and miR-612 suppressed each other in a reciprocal way. Moreover, LUCAT1 promoted HOXA13 expression through inhibition of miR-612, eventually leading to ovarian cancer development. In conclusion, our findings revealed a novel molecular mechanism that LUCAT1/miR-612/HOXA13 pathway modulates ovarian cancer progression.

摘要

越来越多的证据表明,长链非编码 RNA(lncRNA)参与了多种恶性肿瘤的发生,包括卵巢癌。在本研究中,我们专注于长链非编码 RNA 肺癌相关转录本 1(LUCAT1)在卵巢癌进展中的表达和功能。结果表明,LUCAT1 在卵巢癌组织中表达显著上调。此外,LUCAT1 的表达与肿瘤转移和临床分期呈正相关。LUCAT1 表达水平升高会降低卵巢癌患者的生存率。此外,我们发现抑制 LUCAT1 可显著抑制细胞增殖、迁移和侵袭,同时促进细胞凋亡。通过在线预测工具和功能实验,我们证实 LUCAT1 和 HOXA13 是 miR-612 的靶基因。结果表明,LUCAT1 和 miR-612 呈负相关。此外,LUCAT1 通过抑制 miR-612 促进 HOXA13 的表达,进而导致卵巢癌的发生和发展。总之,我们的研究结果揭示了一个新的分子机制,即 LUCAT1/miR-612/HOXA13 通路调节卵巢癌的进展。

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