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长链非编码RNA LINC00673通过与阿片样生长因子受体结合促进上皮性卵巢癌的增殖和转移。

Long noncoding RNA LINC00673 promotes the proliferation and metastasis of epithelial ovarian cancer by associating with opioid growth factor receptor.

作者信息

Zheng Tingting, Qiu Junjun, Li Chunbo, Lin Xiaojing, Tang Xiaoyan, Hua Keqin

机构信息

Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, People's Republic of China.

Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, People's Republic of China.

出版信息

Onco Targets Ther. 2019 Aug 5;12:6145-6156. doi: 10.2147/OTT.S209784. eCollection 2019.

Abstract

PURPOSE

The long noncoding RNA LINC00673 has emerged as an important regulator of cancer development and progression. However, the clinical significance and biological roles of LINC00673 in epithelial ovarian cancer (EOC) remain unclear. In this study, we aimed to explore the oncogenic roles and underlying molecular mechanisms of LINC00673 in EOC.

PATIENTS AND METHODS

The expression levels of LINC00673 in EOC tissues and cell lines were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Real-time cellular analysis (RTCA), flow cytometry, and transwell assays were conducted to investigate cell proliferation, apoptosis, migration and invasion in vitro. Subcutaneous transplanted tumors were established to explore the oncogenic role of LINC00673 in vivo. Differentially expressed genes were analyzed using transcriptome sequencing. Protein levels were determined by Western blot assays.

RESULTS

LINC00673 was upregulated in EOC tissues and cell lines compared to their corresponding normal controls. High expression of LINC00673 was associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, serous histological subtype, lymph node metastasis and poor prognosis in patients with EOC. LINC00673 was also identified as an independent prognostic factor for EOC. In addition, LINC00673 promoted cell migration, invasion and proliferation and inhibited cell apoptosis in vitro and induced tumor growth in vivo. Mechanistically, opioid growth factor receptor () was found to be a potential downstream target gene that mediated the oncogenic effect of LINC00673 in EOC.

CONCLUSION

LINC00673 contributes to EOC proliferation and metastasis and may be a promising prognostic biomarker for EOC patients.

摘要

目的

长链非编码RNA LINC00673已成为癌症发生和发展的重要调节因子。然而,LINC00673在上皮性卵巢癌(EOC)中的临床意义和生物学作用仍不清楚。在本研究中,我们旨在探讨LINC00673在EOC中的致癌作用及潜在分子机制。

患者和方法

采用定量逆转录聚合酶链反应(qRT-PCR)检测EOC组织和细胞系中LINC00673的表达水平。进行实时细胞分析(RTCA)、流式细胞术和Transwell实验,以研究体外细胞增殖、凋亡、迁移和侵袭情况。建立皮下移植瘤模型,以探讨LINC00673在体内的致癌作用。使用转录组测序分析差异表达基因。通过蛋白质免疫印迹法测定蛋白质水平。

结果

与相应的正常对照相比,LINC00673在EOC组织和细胞系中上调。LINC00673的高表达与EOC患者的国际妇产科联盟(FIGO)晚期、浆液性组织学亚型、淋巴结转移及预后不良相关。LINC00673也被确定为EOC的独立预后因素。此外,LINC00673在体外促进细胞迁移、侵袭和增殖,抑制细胞凋亡,并在体内诱导肿瘤生长。机制上,发现阿片样生长因子受体(OGFR)是介导LINC00673在EOC中致癌作用的潜在下游靶基因。

结论

LINC00673促进EOC的增殖和转移,可能是EOC患者有前景的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b3/6689117/1c77bb012a1a/OTT-12-6145-g0001.jpg

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