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长链非编码RNA LOC646029作为竞争性内源RNA,通过miR-627-3p/SPRED1轴抑制卵巢癌进展。

Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis.

作者信息

Zhao Pengfei, Wang Yating, Yu Xiao, Nan Yabing, Liu Shi, Li Bin, Cui Zhumei, Liu Zhihua

机构信息

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

出版信息

Front Med. 2023 Oct;17(5):924-938. doi: 10.1007/s11684-023-1004-z. Epub 2023 Jul 12.

Abstract

Long noncoding RNAs (lncRNAs) play a crucial regulatory role in the development and progression of multiple cancers. However, the potential mechanism by which lncRNAs affect the recurrence and metastasis of ovarian cancer remains unclear. In the current study, the lncRNA LOC646029 was markedly downregulated in metastatic ovarian tumors compared with primary tumors. Gain- and loss-of-function assays demonstrated that LOC646029 inhibits the proliferation, invasiveness, and metastasis of ovarian cancer cells in vivo and in vitro. Moreover, the downregulation of LOC646029 in metastatic ovarian tumors was strongly correlated with poor prognosis. Mechanistically, LOC646029 served as a miR-627-3p sponge to promote the expression of Sprouty-related EVH1 domain-containing protein 1, which is necessary for suppressing tumor metastasis and inhibiting KRAS signaling. Collectively, our results demonstrated that LOC646029 is involved in the progression and metastasis of ovarian cancer, which may be a potential prognostic biomarker.

摘要

长链非编码RNA(lncRNAs)在多种癌症的发生和发展过程中发挥着关键的调控作用。然而,lncRNAs影响卵巢癌复发和转移的潜在机制仍不清楚。在本研究中,与原发性肿瘤相比,lncRNA LOC646029在转移性卵巢肿瘤中显著下调。功能获得和功能缺失实验表明,LOC646029在体内和体外均可抑制卵巢癌细胞的增殖、侵袭和转移。此外,转移性卵巢肿瘤中LOC646029的下调与不良预后密切相关。机制上,LOC646029作为miR-627-3p的海绵,促进含Sprouty相关EVH1结构域蛋白1的表达,该蛋白是抑制肿瘤转移和抑制KRAS信号传导所必需的。综上所述,我们的结果表明LOC646029参与了卵巢癌的进展和转移,可能是一种潜在的预后生物标志物。

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