Negative feedback of miR-29 family TET1 involves in hepatocellular cancer
Negative feedback of miR-29 family TET1 involves in hepatocellular cancer
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DOI：
10.1007/s12032-014-0291-2
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发表时间：
2014-12-01
期刊：
影响因子：
3.4
通讯作者：
Qian, HanGuang
中科院分区：
文献类型：
--
作者：
Lin, Li Li;Wang, Wei;Qian, HanGuang
原发性肝细胞癌（HCC）是最常见的肝癌形式，也是世界上最常见的恶性肿瘤之一。肿瘤抑制基因沉默通过DNA甲基化有助于癌症的形成。10 - 11易位（TET）家族的α -酮谷蛋白-速率依赖性双加氧酶催化5-甲基胞嘧啶依次氧化为5-羟甲基胞嘧啶、5-甲酰胞嘧啶和5-羧基胞嘧啶，最终导致DNA去甲基化。MicroRNAs是一类数量丰富的17-25个核苷酸的小非编码rna，被认为是许多不同生物过程的重要调节因子。在本研究中，我们发现TET1在大多数检查的HCC组织中表达明显降低。我们进一步研究了TET1在增殖、迁移和侵袭中的表达及其功能参与，确定TET1可能具有肿瘤抑制作用。研究证明MiR-29b通过靶向TET1抑制转移，表明miR-29的下调可能通过增强TET1表达参与HCC的癌变和进展。因此，我们阐明了miR-29-TET1下调反馈在HCC发展中的作用，并提出了HCC患者预后鉴定和癌症治疗应用的潜在靶点。
Primary hepatocellular carcinoma (HCC) is the most common form of liver cancer and is one of the most common malignancies worldwide. Tumor suppressor gene silencing through DNA methylation contributes to cancer formation. The ten-eleven translocations (TET) family of alpha-ketogluta-rate-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine to 5-hydroxymethyl- cytosine, 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. MicroRNAs are an abundant class of 17-25 nucleotides small noncoding RNAs, identified as important regulators of many diverse biological processes. In this study, we showed that TET1 expression was obviously reduced in the majority of examined HCC tissues. And we further investigated the expression and functional involvement of TET1 in proliferation, migration and invasion, and determined that TET1 may function as a tumor suppressor. MiR-29b was proved to inhibit metastasis through the targeting of TET1, indicating that downregulation of miR-29 may involve in HCC carcinogenesis and progression through potentiation of TET1 expression. Thus, we elucidated the roles of feedback of miR-29-TET1 downregulation in HCC development and suggested a potential target in identification of the prognosis and application of cancer therapy for HCC patients.