<i>53<scp>BP</scp>1</i> suppresses epithelial–mesenchymal transition by downregulating <i><scp>ZEB</scp>1</i> through micro<scp>RNA</scp>‐200b/429 in breast cancer

Kong, Xiangnan; Ding, Xia; Li, Xiaoyan; Gao, Sumei; Yang, Qifeng

doi:10.1111/cas.12699

Cited by 28 publications

(15 citation statements)

References 38 publications

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“…The mammalian protein 53bp1 is activated in many cell types in response to genotoxic stress, including DSB formation (Anderson et al, 2001 ; Rappold et al, 2001 ; Manis et al, 2004 ; Lukas et al, 2011 ). Previously, various studies reported function of 53bp1 as a tumor suppressor gene in breast cancer (Kong et al, 2015 ). In breast precancerous lesions and cancer tissue 53bp1 immunohistochemical staining was mainly localized in the nuclei of cells (Li et al, 2012 ; Kong et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Detection of DNA Double Strand Breaks by γH2AX Does Not Result in 53bp1 Recruitment in Mouse Retinal Tissues

et al. 2018

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Gene editing is an attractive potential treatment of inherited retinopathies. However, it often relies on endogenous DNA repair. Retinal DNA repair is incompletely characterized in humans and animal models. We investigated recruitment of the double stranded break (DSB) repair complex of γH2AX and 53bp1 in both developing and mature mouse neuroretinas. We evaluated the immunofluorescent retinal expression of these proteins during development (P07-P30) in normal and retinal degeneration models, as well as in potassium bromate induced DSB repair in normal adult (3 months) retinal explants. The two murine retinopathy models used had different mutations in Pde6b: the severe rd1 and the milder rd10 models. Compared to normal adult retina, we found increased numbers of γH2AX positive foci in all retinal neurons of the developing retina in both model and control retinas, as well as in wild type untreated retinal explant cultures. In contrast, the 53bp1 staining of the retina differed both in amount and character between cell types at all ages and in all model systems. There was strong pan nuclear staining in ganglion, amacrine, and horizontal cells, and cone photoreceptors, which was attenuated. Rod photoreceptors did not stain unequivocally. In all samples, 53bp1 stained foci only rarely occurred. Co-localization of 53bp1 and γH2AX staining was a very rare event (< 1% of γH2AX foci in the ONL and < 3% in the INL), suggesting the potential for alternate DSB sensing and repair proteins in the murine retina. At a minimum, murine retinal DSB repair does not appear to follow canonical pathways, and our findings suggests further investigation is warranted.

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Section: Discussionmentioning

confidence: 99%

Detection of DNA Double Strand Breaks by γH2AX Does Not Result in 53bp1 Recruitment in Mouse Retinal Tissues

et al. 2018

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“…Researchers reported that miR-200b-3p regulates several different biological processes by targeting several different cancer-related genes. For instance, miR-200b-3p targeting of Sp1 transcription factor ( SP1 ) regulates cell proliferation and apoptosis [ 14 ], whereas targeting tumor protein p53 binding protein 1 ( 53BP1 ) and the Rho GDP disassociation inhibitor alpha (RHOGDI) pathway suppresses EMT [ 15 , 30 ]. MiR-200b-3p was also reported to play a role in BC lymph node metastasis [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, miR-429-5p was reported to suppress migration and invasion of BC cells via targeting of ZEB1 and CRKL [ 10 ] and to induce apoptosis via targeting of XIAP [ 11 ]. Researchers also reported that miR-429-5p and miR-200b-3p together inhibited EMT [ 30 ]. Our findings validated the roles of miR-200b-3p and miR-429-5p in suppressing TNBC cell migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells

Wang

Song

et al. 2017

Oncotarget

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Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells. Overexpression of miR-200b-3p and miR-429-5p significantly inhibited the proliferation, migration, and invasion of TNBC cells; suppressed the expression of markers for proliferation and metastasis in TNBC cells. We next demonstrated that LIM domain kinase 1 (LIMK1) is a direct target gene of miR-200b-3p and miR-429-5p. Inhibition of LIMK1 reduced the expression and phosphorylation of cofilin 1 (CFL1), which polymerizes and depolymerizes F-actin and G-actin to reorganize cellular actin cytoskeleton. In addition, transfection with mimics for miR-200b-3p and miR-429-5p arrested G2/M and G0/G1 cell cycles respectively, suppressed the expression of the cell cycle–related complexes, cyclin D1/CDK4/CDK6 and cyclin E1/CDK2, in TNBC cells. In conclusion, miR-200b-3p and miR-429-5p suppress proliferation, migration, and invasion in TNBC cells, via the LIMK1/CFL1 pathway. These results provide insight into how specific miRNAs regulate TNBC progression and suggest that the LIMK1/CFL1 pathway is a therapeutic target for treating TNBC.

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“…The death rate due to metastatic breast cancer is nearly the same as 50 years ago . In 2014, approximately 230 000 women in the United States were diagnosed and 40 000 died of invasive breast cancer . Triple‐negative breast cancer (TNBC) is a breast cancer with negative immunohistochemical of estrogen receptor (ER), progesterone receptor (PR), and proto‐oncogene Her‐2.…”

Section: Introductionmentioning

confidence: 99%

“…5 In 2014, approximately 230 000 women in the United States were diagnosed and 40 000 died of invasive breast cancer. 6 Triple-negative breast cancer (TNBC) is a breast cancer with negative immunohistochemical of estrogen receptor (ER), progesterone receptor (PR), and proto-oncogene Her-2. Because of its ER (−), PR (−), Her-2(−), endocrine drugs, such as tamoxifen, for ER (+) and PR (+) breast cancer treatment are ineffective.…”

mentioning

confidence: 99%

Fangjihuangqi Decoction inhibits MDA‐MB‐231 cell invasion in vitro and decreases tumor growth and metastasis in triple‐negative breast cancer xenografts tumor zebrafish model

2020

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Triple‐negative breast cancer (TNBC) is a basal‐like cancer which is considered to be more intrusive, have a poorer prognosis and chemoresistance. TNBC is characterized by the presence of epithelial to mesenchymal transition (EMT) that plays a major role in the progression of the cancer. In the present study, we first use a classic prescription of Chinese medicine Fangjihuangqi Decoction to treat TGFβ1‐induced MDA‐MB‐231 cells in vitro. Our data showed that TGFβ1‐induced MDA‐MB‐231 cell morphology change, promoted MDA‐MB 231 invasion, increased Vimentin expression, and decreased E‐cadherin expression. Further, Fangjihuangqi Decoction‐medicated serum (FHS) treated both MDA‐MB 231 cells and TGFβ1‐induced MDA‐MB‐231 cells. Results showed that Fangjihuangqi Decoction could inhibit cell proliferation, reduce cell invasion, increase E‐cadherin expression, and decrease EMT markers. Secondly, we established a xenograft tumor zebrafish model to assess Fangjihuangqi Decoction inhibition of cancer cell proliferation and invasion. Our results indicated that Fangjihuangqi Decoction could inhibit tumor growth, restrain the sprouts number of tumor neovascularization, and reduce the length of tumor neoplastic lymphatics by increasing E‐cadherin expression and decreasing EMT markers in TNBC xenograft tumor zebrafish model. Overall, our studies provide evidences that Fangjihuangqi Decoction could inhibit TNBC, reverse EMT, and contribute to antimetastasis by increasing E‐cadherin expression and decreasing EMT markers, which provide an experimental basis for clinical application of Fangjihuangqi Decoction on TNBC treatment.

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53BP1 suppresses epithelial–mesenchymal transition by downregulating ZEB1 through microRNA‐200b/429 in breast cancer

Cited by 28 publications

References 38 publications

Detection of DNA Double Strand Breaks by γH2AX Does Not Result in 53bp1 Recruitment in Mouse Retinal Tissues

Detection of DNA Double Strand Breaks by γH2AX Does Not Result in 53bp1 Recruitment in Mouse Retinal Tissues

The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells

Fangjihuangqi Decoction inhibits MDA‐MB‐231 cell invasion in vitro and decreases tumor growth and metastasis in triple‐negative breast cancer xenografts tumor zebrafish model

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