TET1 promotes 5hmC-dependent stemness, and inhibits a 5hmC-independent epithelial-mesenchymal transition, in cervical precancerous lesions

Su, Po Hsuan; Hsu, Yaw Wen; Huang, Rui; Chen, Lin Yu; Chao, Tai-Kuang; Liao, Chun-Ta; Chen, Chien-Wen; Wu, Ting-Jung; Mao, Shih Peng; Balch, Curt; Lai, Hung Cheng

doi:10.1016/j.canlet.2019.01.033

Cited by 34 publications

(25 citation statements)

References 46 publications

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“…Considering that 5mC and TET2 are both closely related to the regulation of DNA methylation, it might be reasonable to hypothesize that 5mC and TET2 also participate in the etiology of the existence or progression of precancerous lesion. In this study, we found that 5hmC and TET2 expressions were both negatively correlated with the histological classification, and here were several possible explanations to the results in our study: (a) 5hmC and TET2 might prevent the formation or repress the progression of breast precancerous lesion via modulating stemness or other related processes, which still need more in vivo and in vitro experiments to validate; (b) 5hmC and TET2 might also inhibit precancerous lesion development and progression via similar mechanism by which they suppress the cancer progression, for instance, repressing malignant behaviors of cancer cells by mediating multiple oncogenic signaling pathways . However, we did not find a statistically significant correlation between 5mC and histopathological classification, which may be due to the dual role of 5mC in cancer pathogenesis found in other cancers, or a relatively small sample size …”

Section: Discussionmentioning

confidence: 51%

“…These studies indicated that TET2 acts as a factor inhibiting tumorigenesis. As for the functions of 5mC, 5hmC, and TET2 in precancerous pathogenesis, it has been reported that TET1 advocates 5hmC‐dependent stemness of the cervical precancerous lesion in vitro . However, to our best knowledge, no direct effect of 5mC or TET2 on precancerous pathogenesis has been reported.…”

Section: Discussionmentioning

confidence: 89%

“…More importantly, there are reports illuminating that 5mC, 5hmC, and TET2 also participate in breast cancer etiology, including the regulation of tumor suppressor genes and DNA methylation . Since that 5mC and 5hmC have been reported in the modulation of precancerous pathogenesis, such as, 5hmC is involved in the stemness in cervical precancerous lesion and 5mC is one of the crucial regulators of DNA methylation dysregulation in colorectal precancerous lesion, and TET2 can catalyze 5mC to 5hmC, we speculated that 5mC, 5hmC, and TET2 may be correlated with the existence or progression of breast precancerous lesion …”

Section: Introductionmentioning

confidence: 96%

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Values of 5mC, 5hmC, and TET2 for identifying the presence and progression of breast precancerous lesion

Zhang

Jin

Zhang

et al. 2019

Clinical Laboratory Analysis

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: This study aimed to evaluate the correlations of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and ten-eleven translocation enzyme 2 (TET2) expressions in lesion tissue with histological classification of breast precancerous lesion. Methods:Eighty-three patients with breast ductal intraepithelial neoplasia (DIN), 20 patients with breast ductal carcinoma in situ with microinvasion (DCIS-MI), and 10 patients with invasive breast cancer were included. Histological classification of the DIN patients was classified as DIN1A, DIN1B, DIN1C, DIN2, and DIN3. 5mC, 5hmC, and TET2 expressions in lesion tissues from biopsy were assessed by immunohistochemistry (IHC) assay.Results: 5hmC and TET2 were negatively associated with histological classification as validated by both IHC score and IHC semi-quantification expression grades in total patients (all P < .05); however, no correlation of 5mC with histological classification was found (all P > .05). 5mC (P = .004) was negatively but 5hmC (P < .001) was positively correlated with TET2, while no association of 5mC with 5hmC was discovered in total patients (P = .078). In addition, 5mC was positively associated with ER expression in total patients (P = .040). In subgroups, 5mC was negatively correlated with 5hmC in DIN1C patients (P = .023) and invasive cancer patients (P = .044), and 5mC was negatively associated with TET2 in DIN1B patients (P = .004) as well as DCIS-MI patients (P = .003).Conclusion: 5hmC and TET2 have the potentials to serve as biomarkers that could assist in the identification of presence and progression of breast precancerous lesion. K E Y W O R D S5-methylcytosine, 5-hydroxymethylcytosine, biomarker, breast precancerous lesion, teneleven translocation enzyme 2 1 | INTRODUC TI ON Breast cancer, the most frequent cancer in women worldwide, attacks approximately 2 088 849 patients and results in roughly 626 679 related deaths in 2018. 1 Breast cancer is featured by the heterogeneous molecular subtypes, such as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) enriched type, and basal-like breast cancer, which is closely related to the therapeutic decision-making and prognosis in clinical setting. 2 In Asia, an elevation of breast cancer incidence could be seen as a R E FE R E N C E S How to cite this article: Zhang Z, Jin Y, Zhang W, et al. Values of 5mC, 5hmC, and TET2 for identifying the presence and progression of breast precancerous lesion. J Clin Lab Anal.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 96%

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Values of 5mC, 5hmC, and TET2 for identifying the presence and progression of breast precancerous lesion

Zhang

Jin

Zhang

et al. 2019

Clinical Laboratory Analysis

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“…Accumulating evidence has discovered that TET1 played important roles in the occurrence and development of neoplastic diseases [23,24]. It has reported that overexpression of TET1 could signi cantly inhibit cell growth, migration and invasion of colon cancer and cervical cancer [23,25,26].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic silencing of TET1 mediated hydroxymethylation of base excision repair pathway during lung carcinogenesis

Chen

et al. 2021

Environmental Pollution

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“…As another example, the circRNA UCK2 simultaneously inhibits invasion and enzalutamide resistance by upregulating TET1 in prostate cancer [167]. TET1 is an important regulator of both cancer stemness and the EMT [226]. The molecular mechanisms of drug resistance regulated by circRNAs exhibit crosstalk with each other, which also lead to complex crosstalk between various malignant phenotypes, such as drug resistance and metastasis.…”

Section: Future Potentialmentioning

confidence: 99%

CircRNAs in anticancer drug resistance: recent advances and future potential

Wang

Jiang

et al. 2020

Mol Cancer

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CircRNAs are a novel class of RNA molecules with a unique closed continuous loop structure. CircRNAs are abundant in eukaryotic cells, have unique stability and tissue specificity, and can play a biological regulatory role at various levels, such as transcriptional and posttranscriptional levels. Numerous studies have indicated that circRNAs serve a crucial purpose in cancer biology. CircRNAs regulate tumor behavioral phenotypes such as proliferation and migration through various molecular mechanisms, such as miRNA sponging, transcriptional regulation, and protein interaction. Recently, several reports have demonstrated that they are also deeply involved in resistance to anticancer drugs, from traditional chemotherapeutic drugs to targeted and immunotherapeutic drugs. This review is the first to summarize the latest research on circRNAs in anticancer drug resistance based on drug classification and to discuss their potential clinical applications.

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TET1 promotes 5hmC-dependent stemness, and inhibits a 5hmC-independent epithelial-mesenchymal transition, in cervical precancerous lesions

Cited by 34 publications

References 46 publications

Values of 5mC, 5hmC, and TET2 for identifying the presence and progression of breast precancerous lesion

Values of 5mC, 5hmC, and TET2 for identifying the presence and progression of breast precancerous lesion

Epigenetic silencing of TET1 mediated hydroxymethylation of base excision repair pathway during lung carcinogenesis

CircRNAs in anticancer drug resistance: recent advances and future potential

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