Wang Xianghu, Gao Zhikui, Liao Juan, Shang Muhe, Li Xiajun, Yin Lihong, Pu Yuepu, Liu Ran
a Key Laboratory of Environmental Medicine Engineering, Ministry of Education , School of Public Health, Southeast University , Nanjing , China.
J Toxicol Environ Health A. 2016;79(9-10):407-18. doi: 10.1080/15287394.2016.1176617.
Esophageal squamous-cell carcinoma (ESCC) is one of the most common tumors worldwide. Recent studies suggested that long noncoding RNAs (lncRNAs) might play a key role in regulating cellular processes and cancer progression. One of the lncRNAs, urothelial carcinoma associated 1 (UCA1), is known to be dysregulated in several cancers, including bladder carcinoma, colorectal, melanoma, breast, gastric, and ESCC. However, contributions of UCA1 to ESCC remain largely undiscovered. In order to understand the role and mechanisms underlying UCA1 in ESCC, the association of UCA1 expression with risk of esophageal cancer development was determined in 106 esophageal cancer tissues of ESCC patients and adjacent normal tissues using real-time reverse-transcription polymerase chain reaction (PCR). The relative expression of UCA1 was significantly reduced in cancer versus adjacent normal tissues suggesting an enhanced risk of esophageal cancer. To investigate the biological functions of UCA1 in ESCC, it was of interest to examine whether overexpression of UCA1 might influence cell proliferation, apoptosis, cell cycle distribution, migration, and invasion in vitro using EC109 cells. Our results demonstrated that UCA1 decreased cell proliferation, migration, invasion, and cell cycle progression of EC109 cells. Further, mRNA microarray analysis of overexpressed UCA1 in EC109 cells revealed that abnormal expression of UCA1 also inhibited the Wnt signaling pathway. Gene levels of DKK1 were elevated while C-myc fell significantly in overexpressed UCA1 EC109 cells. Interestingly, Western blot demonstrated no significant differences in relative expression of CTNNB1 (β-catenin) but marked reduction in β-catenin (active form) levels in both total and nuclear proteins. These results suggest that UCA1 may inhibit ESCC growth by regulating the Wnt signaling pathway. In conclusion, UCA1 may be a novel biomarker involved in ESCC development that may provide a potential therapeutic target for ESCC.
食管鳞状细胞癌（ESCC）是全球最常见的肿瘤之一。最近的研究表明，长链非编码RNA（lncRNA）可能在调节细胞过程和癌症进展中起关键作用。其中一种lncRNA，即尿路上皮癌相关1（UCA1），已知在包括膀胱癌、结直肠癌、黑色素瘤、乳腺癌、胃癌和ESCC在内的多种癌症中表达失调。然而，UCA1对ESCC的作用在很大程度上仍未被发现。为了了解UCA1在ESCC中的作用和潜在机制，我们使用实时逆转录聚合酶链反应（PCR）检测了106例ESCC患者的食管癌组织及癌旁正常组织中UCA1的表达，并分析其与食管癌发生风险的关系。结果显示，与癌旁正常组织相比，癌组织中UCA1的相对表达显著降低，提示食管癌风险增加。为了研究UCA1在ESCC中的生物学功能，我们检测了UCA1过表达对EC109细胞体外增殖、凋亡、细胞周期分布、迁移和侵袭的影响。结果表明，UCA1可抑制EC109细胞的增殖、迁移、侵袭及细胞周期进程。此外，对过表达UCA1的EC109细胞进行mRNA微阵列分析发现，UCA1的异常表达还抑制了Wnt信号通路。在过表达UCA1的EC109细胞中，DKK1基因水平升高，而C-myc水平显著下降。有趣的是，蛋白质免疫印迹法显示，CTNNB1（β-连环蛋白）的相对表达无显著差异，但总蛋白和核蛋白中β-连环蛋白（活性形式）水平显著降低。这些结果表明，UCA1可能通过调节Wnt信号通路抑制ESCC的生长。总之，UCA1可能是参与ESCC发生发展的新型生物标志物，有望为ESCC提供潜在的治疗靶点。
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