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Abstract：
Homo sapiens chromosome 2 clone RP11-339H12 (AC010883.5) is a dysregulated long non-coding RNA (lncRNA) that has never been investigated in cervical cancer (CC). Thus, the potential function and molecular mechanism remain unclear. Our study explored the biological function of AC010883.5 to determine the underlying mechanisms in CC and provide potential therapeutic targets for improving the clinical treatment strategy. We used quantitative real-time polymerase chain reaction to measure mitochondrial RNA levels and western blot to measure the protein levels of target genes. Further, we used Cell Counting Kit-8 and 5-Bromo-2\'-deoxyuridine incorporation assays to evaluate cell proliferation in vitro. Cell apoptosis was analyzed by flow cytometry. Cell invasion was analyzed by wound healing and Transwell migration assays was ued to analyze cell migration. Finally, the biological function and mechanism of AC010883.5 in CC growth were evaluated by in vivo xenograft assay. AC010883.5 was enhanced in CC tissues and cell lines, and enhanced AC010883.5 expression accelerated CC cell proliferation, migration, and invasion and induced epithelial-mesenchymal transition in vitro and in vivo. AC010883.5 also activated the mitogen-activated protein kinase (MAPK) signaling pathway by promoting phosphorylation of extracellular signal-regulated kinase 1/2 (i.e., ERK1/2) and MAPK kinase 1/2 (i.e., MEK1/2). Blocking the MAPK signaling pathway could counteract the pro-proliferative, pro-migrative, and pro-invasive effects of AC010883.5 over-expression. We found that the lncRNA, AC010883.5, is an oncogenic molecule involved in CC tumor progression via dysregulation of the MAPK signaling pathway, implying that AC010883.5 could be a tumor progression and therapeutic response biomarker.
摘要：
智人2号染色体克隆RP11-339H12（AC010883.5）是一种失调的长非编码RNA（lncRNA），从未在宫颈癌（CC）中进行过研究。因此，潜在的功能和分子机制尚不清楚。我们的研究探索了AC010883.5的生物学功能，以确定CC的潜在机制，并为改善临床治疗策略提供潜在的治疗靶点。我们使用定量实时聚合酶链反应来测量线粒体RNA水平，并使用蛋白质印迹来测量靶基因的蛋白质水平。Further,我们使用细胞计数试剂盒-8和5-溴-2'-脱氧尿苷掺入测定法来评估体外细胞增殖。通过流式细胞术分析细胞凋亡。通过伤口愈合分析细胞侵袭,并使用Transwell迁移测定法分析细胞迁移。最后,通过体内异种移植实验评估AC010883.5在CC生长中的生物学功能和机制。AC010883.5在CC组织和细胞系中增强，和增强AC010883.5的表达加速CC细胞增殖，迁移,以及在体外和体内的侵袭和诱导的上皮-间质转化。AC010883.5还通过促进细胞外信号调节激酶1/2的磷酸化来激活丝裂原活化蛋白激酶（MAPK）信号通路（即ERK1/2）和MAPK激酶1/2（即MEK1/2)。阻断MAPK信号通路可以抵消促增殖,亲移民，AC010883.5过表达的促侵袭作用。我们发现lncRNA,AC010883.5是通过MAPK信号通路失调参与CC肿瘤进展的致癌分子，这意味着AC010883.5可能是肿瘤进展和治疗反应的生物标志物。
