Zhang Qian, Zheng Jindan, Liu Lili
Gynecology Department, The First Affiliated Hospital, Jinzhou Medical University, No.2 of the People Street, Guta District, Jinzhou, 121001 Liaoning China.
Cancer Cell Int. 2019 Nov 20;19:304. doi: 10.1186/s12935-019-1030-8. eCollection 2019.
Cervical cancer (CC) is the fourth leading cause of cancer-associated death in women worldwide. Recently, long noncoding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) has been demonstrated to involve in the initiation and progression of human cancers. However, to date, the clinical and functional significance of PCGEM1 expression in CC progression remains unknown.
qRT-PCR was performed to investigate PCGEM1 expression levels in CC tissues and cell lines. The effect of PCGEM1 on CC cells was assessed by gain- and loss-of-function assays. MS2-binding sequences-MS2-binding protein-based RIP assay (MS2-RIP), RNA pull-down and Luciferase reporter assays were performed to investigate the interaction between PCGEM1 and miR-182. The association between miR-182 and F-box and WD repeat domain containing 11 (FBXW11) was verified by luciferase reporter assay. The effect of PCGEM1 on the NF-κB and β-catenin/TCF signaling pathways was determined by luciferase reporter assay.
Our present study showed that PCGEM1 was significantly upregulated in CC tissues and cell lines. Overexpression of PCGEM1 was correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node, distant metastasis and poor prognosis in CC patients. Functionally, PCGEM1 promoted cell proliferation, cell cycle progression, migration and invasion, while suppressed cell apoptosis in CC cells. Further mechanistic investigation revealed that PCGEM1 associated with miR-182 and suppressed its expression. PCGEM1 could act as a competing endogenous (ceRNA) of oncogene F-box and WD repeat domain containing 11 (FBXW11) for miR-182 in CC cells. Additionally, PCGEM1 was capable to activate the NF-κB and β-catenin/TCF signaling pathways, which was reversed by inhibition of FBXW11.
In conclusion, our findings demonstrated that PCGEM1-miR-182-FBXW11 axis play an important role in CC progression, and indicated a promising therapeutic target for CC patients.
宫颈癌（CC）是全球女性癌症相关死亡的第四大主要原因。最近，长链非编码RNA（lncRNA）前列腺癌基因表达标志物1（PCGEM1）已被证明参与人类癌症的发生和发展。然而，迄今为止，PCGEM1表达在CC进展中的临床和功能意义仍不清楚。
采用qRT-PCR检测CC组织和细胞系中PCGEM1的表达水平。通过功能获得和功能缺失实验评估PCGEM1对CC细胞的影响。进行基于MS2结合序列-MS2结合蛋白的RIP实验（MS2-RIP）、RNA下拉实验和荧光素酶报告基因实验，以研究PCGEM1与miR-182之间的相互作用。通过荧光素酶报告基因实验验证miR-182与含F-box和WD重复结构域11（FBXW11）之间的关联。通过荧光素酶报告基因实验确定PCGEM1对NF-κB和β-连环蛋白/TCF信号通路的影响。
我们目前的研究表明，PCGEM1在CC组织和细胞系中显著上调。PCGEM1的过表达与CC患者的国际妇产科联盟（FIGO）晚期、淋巴结转移、远处转移及预后不良相关。在功能上，PCGEM1促进CC细胞的增殖、细胞周期进程、迁移和侵袭，同时抑制细胞凋亡。进一步的机制研究表明PCGEM1与miR-182相关并抑制其表达。在CC细胞中，PCGEM1可以作为致癌基因含F-box和WD重复结构域11（FBXW11）的竞争性内源RNA（ceRNA）与miR-182结合。此外，PCGEM1能够激活NF-κB和β-连环蛋白/TCF信号通路，而抑制FBXW11可逆转这种激活作用。
总之，我们的研究结果表明PCGEM1-miR-182-FBXW11轴在CC进展中起重要作用，并为CC患者指明了一个有前景的治疗靶点。
