Tumor-Suppressive Function of miR-139-5p in Esophageal Squamous Cell Carcinoma
Tumor-Suppressive Function of miR-139-5p in Esophageal Squamous Cell Carcinoma
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miR-139-5p 在食管鳞状细胞癌中的抑癌功能
DOI：
10.1371/journal.pone.0077068
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发表时间：
2013-10-18
期刊：
影响因子：
3.7
通讯作者：
Kim, Sun Jung
中科院分区：
文献类型：
--
作者：
Liu, Ran;Yang, Miao;Kim, Sun Jung
最近的研究已经证明miR-139-5p在肿瘤发生中的可能功能。然而，miR-139-5p在癌症中的确切机制尚不清楚。在这项研究中，我们在106对食管鳞状细胞癌患者的食管癌和邻近非癌组织中评估了miR-139-5p表达与食管鳞状细胞癌（ESCC）的关系。通过评估细胞增殖和细胞周期状态、迁移活性和侵袭能力以及细胞凋亡来衡量miR-139-5p的抑瘤特性。采用荧光素酶报告基因法和Western blot分析确定miR-139-5p调控的靶基因。检测ESCC患者中miR-139-5p靶基因NR5A2的mRNA水平。结果显示，miR-139-5p水平降低与ESCC淋巴结转移相关。我们研究了MiR-139-5p通过靶向致癌基因NR5A2的3'UTR，诱导细胞周期阻滞在G0/G1期，并抑制食管癌细胞的侵袭能力。证实Cyclin E1和MMP9分别参与NR5A2诱导的细胞周期阻滞和侵袭性抑制。Pearson相关分析进一步证实miR-139-5p与NR5A2表达呈显著负相关。结果表明，miR-139-5p在人类ESCC中发挥生长和侵袭性抑制功能，这表明miR-139-5p是早期诊断和预后的潜在生物标志物，是ESCC的治疗靶点。
Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3′UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC.