**Author details**

and the consequent loss of 5-hmC. Indeed, miR-21-5p has been confirmed to target Tet1 in colorectal cancer (CRC), serving as a biomarker for diagnostics and prognostics in CRC [98]. Similarly, miR-4284 directly targeting Tet1 mRNA downregulates TET1 levels of both mRNA and protein in human gastric cancer SGC-7901 cells, and thus serves as an oncogenic marker [99], suggesting that miR-4284 could provide a potential target for gastric cancer therapy.

Some miRNAs are reported to function as both a suppressor and a promoter in some cancers such as miR29b in breast cancer (BC) cells by regulation of BC cell proliferation, metastasis, and epithelial-mesenchymal transition (EMT). Significantly decreased expression of miR-29b in BC samples and cell lines suggests the role of TET1 as a BC suppressor. However, miR-29b overexpression promotes cell proliferation, colony formation, migration, and EMT, indicating that miR-29b functions as a BC promoter [103]. In vitro assay TET1 has been identified as one of the miR-29b targets, and it turns out that overexpression of miR29b leads to TET1 downregulation-mediated promotion of proliferation, colony formation, invasion, and EMT in GC cells such as MDA-MB-231 and MCF-7. Further study showed that the TET1-mediated suppression of the BC attributed to TET1 conferred disruption of ZEB2 expression by binding to the promoter of ZEB2. While the miR-29b/TET1/ZEB2 pathway offers understanding for the mechanism of miR-29b and TET1-mediated BC promotion, the suppression mechanism

In the past decades, particularly recent years, significant achievements have been made in epigenetic study particularly 5-mC and its derivatives such as 5-hmC, 5-fC, and 5-caC, in understanding the generation, dynamic alteration, machinery, distribution, and biological functions and connection between the modifications and the pathogenesis of diseases such as neurological disorders and cancers. However, a large number of unknown epigenetic events related to pathogenesis of many diseases particularly cancers remain to be elusive. Although the individual members of the methyltransferase complexes (writer) for cytosine modifications have been characterized, their coordination in conducting the methylation in response to tumorigenesis has not yet been comprehensively investigated. Similarly, the functional study on the TET proteins (the erasers for methylation) stays only at the conversion of 5-mC to 5-hmC, identification of the targeting miRNAs, and identification of serving as tumor suppressors or promoters by several known mechanisms. However, it is logical to speculate that as such huge protein molecules, TET proteins may have much more unidentified functions. Further study on the unknown functions will provide essential information for dissecting the cancer pathogenesis. First, only limited information is available for the physical interaction components of the TETs; identification of the TET interaction proteins may help us better understand how and where the TETs are recruited to function as demethylase to maintain the dynamic balance of 5-mC/5-hmC and the chromatin remodeling. Then, identification of other functions of TETs other than demethylase will be of importance. Given that the 5-hmC is not so much serving an intermediate of demethylation as the important dynamic 5-hmC

*3.2.4. Dual function of miRNA by interaction with Tet mRNA 3'UTRs*

for TET1 remains to be elusive in GC [104].

**4. Concluding remarks**

196 Chromatin and Epigenetics

Cuili Ma1 , Pengfei Ji2 , Nina Xie3 and Yujing Li4 \*

\*Address all correspondence to: yli29@emory.edu

1 Department of Internal Medicine, Qingdao Agricultural University Associated Hospital, Qingdao, Shandong, PR China

2 Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA

3 Department of Neurology of Xiangya Hospital, Central South University, Changsha, Hunan, China

4 Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA
