Zhuang Xiao-Hong, Liu Ying, Li Jin-Ling
Department of Obstetrics and Gynecology, People's Hospital of Linyi Economic Development Area, Linyi, Shandong, China.
Department of Gynecology, The Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao, Shandong, China.
Biosci Rep. 2019 Aug 2;39(8). doi: 10.1042/BSR20190906. Print 2019 Aug 30.
Long noncoding RNA HOXB cluster antisense RNA 3 (HOXB-AS3) has been reported to be dysregulated in several tumors. The present study mainly aims at the investigation in how HOXB-AS3 works in epithelial ovarian cancer (EOC) and to elucidate the mechanism involved. Initially, 'GEPIA' was mined to examine the differential expression levels and prognostic value of HOXB-AS3 in EOC patients. The expression of HOXB-AS3 in EOC cell lines and patient specimens was examined with quantitative RT-PCR. Simultaneously, the correlation of HOXB-AS3 expression with a variety of clinicopathological factors and patient survival was analyzed. MTT, colony formation and flow cytometry assays were performed to analyze the cell viability of EOC cells. Wound healing and Transwell assays were carried out to determine EOC cells' capability of migrating and invading. The impact of HOXB-AS3 on EMT and Wnt/β-catenin signaling was explored with the approach of Western blot. We found that in both EOC cell lines and tissues, HOXB-AS3 expression was significantly up-regulated, and its high expression was an independent prognostic marker of poor outcome for EOC patients. loss-of-function assays revealed that HOXB-AS3 knockdown inhibited EOC cells proliferation, migration, invasion and EMT, and induced EOC cells' apoptosis. Furthermore, we validated that down-regulated HOXB-AS3 attenuated the activity of Wnt/β-catenin signaling to suppress the invasion, migration and proliferation of EOC cells. To sum up, the present study came up with the conclusion that HOXB-AS3 acts as an oncogenic gene in EOC progression through HOXB-AS3-Wnt/β-catenin signaling regulation, providing a novel insight into EOC tumorigenesis.
据报道，长链非编码RNA HOXB簇反义RNA 3（HOXB-AS3）在多种肿瘤中表达失调。本研究主要旨在探究HOXB-AS3在上皮性卵巢癌（EOC）中的作用机制。首先，利用“GEPIA”数据库检测HOXB-AS3在EOC患者中的差异表达水平及预后价值。采用定量RT-PCR检测HOXB-AS3在EOC细胞系和患者标本中的表达。同时，分析HOXB-AS3表达与多种临床病理因素及患者生存的相关性。通过MTT、集落形成和流式细胞术检测分析EOC细胞的活力。采用伤口愈合实验和Transwell实验检测EOC细胞的迁移和侵袭能力。通过蛋白质印迹法探讨HOXB-AS3对上皮-间质转化（EMT）和Wnt/β-连环蛋白信号通路的影响。我们发现，在EOC细胞系和组织中，HOXB-AS3表达均显著上调，其高表达是EOC患者预后不良的独立预后标志物。功能丧失实验表明，敲低HOXB-AS3可抑制EOC细胞的增殖、迁移、侵袭和EMT，并诱导EOC细胞凋亡。此外，我们证实下调HOXB-AS3可减弱Wnt/β-连环蛋白信号通路的活性，从而抑制EOC细胞的侵袭、迁移和增殖。综上所述，本研究得出结论，HOXB-AS3通过HOXB-AS3-Wnt/β-连环蛋白信号通路调控在EOC进展中发挥致癌基因的作用，为EOC的肿瘤发生提供了新的见解。
