MiR-29b/TET1/ZEB2 signaling axis regulates metastatic properties and epithelial-mesenchymal transition in breast cancer cells

Wang, Hua; An, Xinglan; Yu, Hao; Zhang, Sheng; Tang, Bo; Zhang, Xueming; Li, Ziyi

doi:10.18632/oncotarget.22183

Cited by 43 publications

(36 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it has been found that TET1 bound to the promoter of ZEB2 and inhibited cancer cell proliferation, colony formation and invasion ( Fig. 7) [35].…”

Section: Discussionmentioning

confidence: 92%

Epigenetic reprogramming of primary pancreatic cancer cells counteracts their in vivo tumourigenicity

et al. 2019

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) arises through accumulation of multiple genetic alterations. However, cancer cells also acquire and depend on cancer-specific epigenetic changes. To conclusively demonstrate the crucial relevance of the epigenetic programme for the tumourigenicity of the cancer cells, we used cellular reprogramming technology to reverse these epigenetic changes. We reprogrammed human PDAC cultures using three different techniques-(1) lentivirally via induction of Yamanaka Factors (OSKM), (2) the pluripotency-associated gene OCT4 and the microRNA mir-302, or (3) using episomal vectors as a safer alternative without genomic integration. We found that induction with episomal vectors was the most efficient method to reprogram primary human PDAC cultures as well as primary human fibroblasts that served as positive controls. Successful reprogramming was evidenced by immunostaining, alkaline phosphatase staining, and realtime PCR. Intriguingly, reprogramming of primary human PDAC cultures drastically reduced their in vivo tumourigenicity, which appeared to be driven by the cells' enhanced differentiation and loss of stemness upon transplantation. Our study demonstrates that reprogrammed primary PDAC cultures are functionally distinct from parental PDAC cells resulting in drastically reduced tumourigenicity in vitro and in vivo. Thus, epigenetic alterations account at least in part for the tumourigenicity and aggressiveness of pancreatic cancer, supporting the notion that epigenetic modulators could be a suitable approach to improve the dismal outcome of patients with pancreatic cancer.

show abstract

“…Furthermore, it has been found that TET1 bound to the promoter of ZEB2 and inhibited cancer cell proliferation, colony formation and invasion ( Fig. 7) [35].…”

Section: Discussionmentioning

confidence: 92%

Epigenetic reprogramming of primary pancreatic cancer cells counteracts their in vivo tumourigenicity

et al. 2019

View full text Add to dashboard Cite

show abstract

“…41 In addition, He et al reported that ZEB2 could form functional protein complexes with CdGAP in a GAP-independent manner and then regulate E-cadherin expression, thereby promoting the proliferation and metastasis of BC cells. 42 Both miR-204/ZEB2 axis 43 and miR-29b/TET1/ZEB2 axis 44 were involved in EMT and malignant evolution of BC cells. Zou et al showed that FAT10 could bind to ZEB2 directly, reducing its ubiquitination and enhancing its protein stability in BC cells, which contributed to the progress of BC.…”

Section: Discussionmentioning

confidence: 99%

<p>Upregulation Of miR-153 Inhibits Triple-Negative Breast Cancer Progression By Targeting ZEB2-Mediated EMT And Contributes To Better Prognosis</p>

Shi

Fan

et al. 2019

OTT

View full text Add to dashboard Cite

Background: Triple-negative breast cancer (TNBC) is the most malignant type of breast cancer. MicroRNAs (miRs) and their corresponding molecular targets are associated with the occurrence and development of various human malignancies. However, the roles of the microRNA-153 (miR-153) and zinc finger E-box-binding homeobox 2 (ZEB2)-induced epithelial-mesenchymal transition (EMT) in TNBC and predictive effect of miR-153 on the prognosis of TNBC have not been fully elucidated. Materials and methods: Relative miR-153 expression level was examined by RT-qPCR assay in TNBC tissues of 60 patients and TNBC cell lines (SKBR3, BT-549 and MDA-MB-231). Cell proliferation ability, invasion ability and migration ability were measured by CCK8 assay, Transwell invasion assay and wound healing assay, respectively. Luciferase reporting experiment was used to confirm that there was a miR-153-binding site in ZEB2 3ʹ-UTR. The expression of ZEB2 in tissues and its relationship with miR-153 were analyzed with immunohistochemistry method. Relative ZEB2, E-cadherin, N-cadherin and Vimentin mRNA and protein expression levels were observed with RT-qPCR and Western blot, respectively. Based on risk factors, a prognostic model was established according to the Cox proportional risk model, and the prognostic risk factors of TNBC patients were predicted and analyzed. Results: The expression of miR-153 in TNBC tissues and cells was declined (all P<0.01), and upregulation of miR-153 inhibited proliferation, invasion and migration of TNBC cells (all P<0.01). In addition, miR-153 regulated ZEB2/EMT link in TNBC, and ZEB2 overexpression reversed the tumor-suppressive effect of miR-153 in TNBC. Moreover, miR-153 was an independent predictive factor that was associated with excellent prognosis in TNBC patients. Conclusion: miR-153 may inhibit TNBC proliferation, invasion and migration by regulating ZEB2/EMT link. Therefore, miR-153 is expected to be a molecular target and prognostic marker for TNBC.

show abstract

“…The MiR‐371 family can be used as the plasma biomarkers for monitoring undifferentiated and potentially malignant human pluripotent stem cells (Salvatori et al, ). Besides, some groups have reported that miR‐29b‐3p plays important roles in cell apoptosis, inflammation, and oxidative stress (Jing et al, ; H. Wang et al, ; Xing et al, ; Zhang et al, ). MiR‐29 can be used as a clinical marker of disease.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have revealed that miR‐29b plays important roles in a variety of diseases (Langsch et al, ; S. Zhou et al, ). This miRNA can prevent doxorubicin‐induced myocardial apoptosis by targeting BAX (Jing, Yang, Jiang, Chen, & Wang, ), inhibit high‐mobility group box 1/TLR4 signallling in liver fibrosis (Zhang et al, ), inhibit breast cancer via targeting the DNA modifying enzyme TET1 (H. Wang et al, ), and alleviate IgAN pathogenesis via targeting the cyclin‐dependent kinase 6 (Xing et al, ). However, there are no reports of the effects of miR‐29b‐3p on II/R injury.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

Dai

Zhang

Han

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

Background and Purpose The microRNA miR‐29b‐3p shows important roles in regulating apoptosis and inflammation. However, its effects on intestinal ischaemia/reperfusion (II/R) injury have not been reported. Here we have investigated the functions of miR‐29b‐3p on II/R injury on order to find drug targets to treat the injury. Experimental Approach Two models ‐ in vitro hypoxia/reoxygenation (H/R) of IEC‐6 cells; in vivo, II/R injury in C57BL/6 mice were used. Western blotting and dual‐luciferase reporter assays were used and mimic and siRNA transfection tests were applied to assess the effects of miR‐29b‐3p on II/R injury via targeting TNF receptor‐associated factor 3 (TRAF3). Key Results The H/R procedure decreased cell viability and promoted inflammation and apoptosis in IEC‐6 cells, and the II/R procedure also promoted intestinal inflammation and apoptosis in mice. Expression levels of miR‐29b‐3p were decreased in H/R‐induced cells and II/R‐induced intestinal tissues of mice compared with control group or sham group, which directly targeted TRAF3. Decreased miR‐29b‐3p level markedly increased TRAF3 expression via activating TGF‐α‐activated kinase 1 phosphorylation, increasing NF‐κB (p65) levels to promote inflammation, up‐regulating Bcl2‐associated X expression, and down‐regulating Bcl‐2 expression to trigger apoptosis. In addition, the miR‐29b‐3p mimetic and TRAF3 siRNA in IEC‐6 cells markedly suppressed apoptosis and inflammation to alleviate II/R injury via inhibiting TRAF3 signallimg. Conclusions and Implications The miR‐29b‐3p played a critical role in II/R injury, via targeting TRAF3, which should be considered as a significant drug target to treat the disease.

show abstract

MiR-29b/TET1/ZEB2 signaling axis regulates metastatic properties and epithelial-mesenchymal transition in breast cancer cells

Cited by 43 publications

References 56 publications

Epigenetic reprogramming of primary pancreatic cancer cells counteracts their in vivo tumourigenicity

Epigenetic reprogramming of primary pancreatic cancer cells counteracts their in vivo tumourigenicity

<p>Upregulation Of miR-153 Inhibits Triple-Negative Breast Cancer Progression By Targeting ZEB2-Mediated EMT And Contributes To Better Prognosis</p>

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

Contact Info

Product

Resources

About