Dou Xiaoqing, Zhou Qun, Wen Mingxiao, Xu Jiangyan, Zhu Yingping, Zhang Shuzhen, Xu Xianli
Department of Gynecology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China.
Front Pharmacol. 2020 Jan 31;10:1700. doi: 10.3389/fphar.2019.01700. eCollection 2019.
Although the functions of long noncoding RNA (lncRNA) called FOXD2 adjacent opposite strand RNA 1 () have been well studied in multiple human cancer types, its expression status and detailed roles in cervical cancer remain unknown and merit investigation. This study was aimed at assessing expression in cervical cancer and at determining its effects on the aggressive behavior of cervical cancer and . Expression of in cervical cancer tissues and cell lines was determined reverse-transcription quantitative PCR. The effects of on cervical cancer cells were examined by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow-cytometric analysis, migration and invasion assays, and an tumorigenicity assay. was found to be significantly upregulated in cervical cancer tissues and cell lines. High expression was notably linked with the Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and depth of cervical invasion in patients with cervical cancer. Kaplan-Meier survival analysis revealed significantly shorter overall survival of patients when the tumor expression of was higher in comparison with those in patients with lower expression. functional assays revealed that downregulation of led to suppression of proliferation, migration, and invasiveness as well as to the induction of apoptosis of cervical cancer cells. In addition, silencing hindered tumor growth . Mechanism investigation revealed that functioned as a molecular sponge of microRNA-760 (miR-760). Furthermore, hepatoma-derived growth factor () was validated as a direct target gene of miR-760 in cervical cancer cells. Moreover, an miR-760 knockdown reversed the effects of silencing on cervical cancer cells. possesses significant oncogenic activity in cervical cancer progression; this activity is mediated by sponging of miR-760 with consequent upregulation of HDGF. The -miR-760-HDGF axis might harbor promising targets for novel treatment strategies of cervical cancer.
尽管名为FOXD2相邻反义链RNA 1（）的长链非编码RNA（lncRNA）在多种人类癌症类型中的功能已得到充分研究，但其在宫颈癌中的表达状态和详细作用仍不清楚，值得研究。本研究旨在评估其在宫颈癌中的表达，并确定其对宫颈癌侵袭性行为的影响。通过逆转录定量PCR测定其在宫颈癌组织和细胞系中的表达。通过3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2-H-四氮唑溴盐（MTT）法、流式细胞术分析、迁移和侵袭试验以及体内肿瘤igenicity试验检测其对宫颈癌细胞的影响。发现其在宫颈癌组织和细胞系中显著上调。高表达与宫颈癌患者的国际妇产科联合会（FIGO）分期、淋巴结转移和宫颈浸润深度显著相关。Kaplan-Meier生存分析显示，与低表达患者相比，肿瘤中表达较高的患者总生存期显著缩短。功能试验表明，下调导致宫颈癌细胞增殖、迁移和侵袭性的抑制以及凋亡的诱导。此外，沉默阻碍了肿瘤生长。机制研究表明，可作为微小RNA-760（miR-760）的分子海绵发挥作用。此外，肝癌衍生生长因子（）被证实为宫颈癌细胞中miR-760的直接靶基因。此外，miR-760敲低可逆转沉默对宫颈癌细胞的影响。在宫颈癌进展中具有显著的致癌活性；这种活性是通过海绵化miR-760并随后上调HDGF介导的。-miR-760-HDGF轴可能为宫颈癌的新治疗策略提供有前景的靶点。
