Cui Xiao-Bin, Peng Hao, Li Ran-Ran, Mu Jian-Qin, Yang Lan, Li Na, Liu Chun-Xia, Hu Jian-Ming, Li Shu-Gang, Wei Yutao, Zhou Hong, Li Feng, Chen Yun-Zhao
Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, China.
Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Oncotarget. 2017 Sep 27;8(54):92454-92469. doi: 10.18632/oncotarget.21384. eCollection 2017 Nov 3.
Esophageal squamous cell carcinoma (ESCC) is one of the frequent malignant tumors with poor prognosis worldwide. Identifying the prognostic biomarkers and potential mechanisms of such tumors has attracted increasing interest in esophageal cancer biology. Our previous study showed that phospholipase C elipson 1 (PLCE1) expression is up-regulated and associated with disease progression in esophageal carcinoma. MicroRNAs (miRNAs) play vital roles in regulating its target gene expression. However, studies on miRNA-regulated PLCE1 expression and its cellular function are still very few. We found that miR-34a is significantly expressed lower in ESCC tissues. We further showed that PLCE1 is a direct functional target gene of miR-34a, and the functional roles of miR-34a in ESCC cell lines were also determined through gain- and loss-of-function analyses. Results revealed that miR-34a functions as a tumor suppressor by inhibiting the proliferation, migration, and EMT phenotype, as well as promoting apoptosis of ESCC cell lines. Moreover, PLCE1 is overexpressed in ESCC tumors and promotes tumorigenicity and vitro. PLCE1 expression is negatively correlated with miR-34a profiles in ESCC tissues. Our data suggest that miR-34a exerts its anti-cancer function by suppressing PLCE1. The newly identified miR-34a/PLCE1 axis partially illustrates the molecular mechanism of ESCC metastasis and represents a new candidate therapeutic target for ESCC treatment.
食管鳞状细胞癌(ESCC)是全球范围内常见的恶性肿瘤之一,预后较差。识别此类肿瘤的预后生物标志物和潜在机制已引起食管癌生物学领域越来越多的关注。我们之前的研究表明,磷脂酶Cε1(PLCE1)的表达上调,且与食管癌的疾病进展相关。微小RNA(miRNA)在调节其靶基因表达中发挥着至关重要的作用。然而,关于miRNA调节PLCE1表达及其细胞功能的研究仍然很少。我们发现miR-34a在ESCC组织中的表达显著降低。我们进一步表明,PLCE1是miR-34a的直接功能靶基因,并且通过功能获得和功能缺失分析确定了miR-34a在ESCC细胞系中的功能作用。结果显示,miR-34a通过抑制ESCC细胞系的增殖、迁移和EMT表型以及促进其凋亡而发挥肿瘤抑制作用。此外,PLCE1在ESCC肿瘤中过表达,并促进肿瘤发生和体外生长。在ESCC组织中,PLCE1的表达与miR-34a的表达水平呈负相关。我们的数据表明,miR-34a通过抑制PLCE1发挥其抗癌功能。新发现的miR-34a/PLCE1轴部分阐明了ESCC转移的分子机制,并代表了ESCC治疗的一个新的候选治疗靶点。