The Experts below are selected from a list of 244119 Experts worldwide ranked by ideXlab platform
Michael Borre - One of the best experts on this subject based on the ideXlab platform.
-
coordinated epigenetic repression of the mir 200 family and mir 205 in invasive bladder cancer
International Journal of Cancer, 2011Co-Authors: Erik D Wiklund, Jesper B. Bramsen, Toby Hulf, Lars Dyrskjøt, Ramshanker Ramanathan, Thomas B. Hansen, Sune B. Villadsen, Shan Gao, Marie Stampe Ostenfeld, Michael BorreAbstract:MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and Mir-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the transcriptional repressors of E-cadherin, ZEB1 and ZEB2. ZEB1 is also known to repress miR-200c-141 transcription in a negative feedback loop, but otherwise little is known about the transcriptional regulation of the miR-200 family and Mir-205. Recently, miR-200 silencing was also reported in cancer stem cells, implying that miR-200 deregulation is a key event in multiple levels of tumor biology. However, what prevents miR-200 expression remains largely unanswered. Here we report concerted transcriptional regulation of the miR-200 and Mir-205 loci in bladder tumors and bladder cell lines. Using a combination of miRNA expression arrays, qPCR assays and mass spectrometry DNA methylation analyses, we show that the miR-200 and Mir-205 loci are specifically silenced and gain promoter hypermethylation and repressive chromatin marks in muscle invasive bladder tumors and undifferentiated bladder cell lines. Moreover, we report that miR-200c expression is significantly correlated with early stage T1 bladder tumor progression, and propose miR-200 and Mir-205 silencing and DNA hypermethylation as possible prognostic markers in bladder cancer. In addition, we observe that the mesoderm transcription factor TWIST1 and miR-200 expression are inversely correlated in bladder tumor samples and cell lines. TWIST1 associates directly with the miR-200 and Mir-205 promoters, and may act as a repressor of miR-200 and Mir-205 expression.
-
Coordinated epigenetic repression of the miR‐200 family and miR‐205 in invasive bladder cancer
International journal of cancer, 2011Co-Authors: Erik D Wiklund, Jesper B. Bramsen, Toby Hulf, Lars Dyrskjøt, Ramshanker Ramanathan, Thomas B. Hansen, Sune B. Villadsen, Shan Gao, Marie Stampe Ostenfeld, Michael BorreAbstract:MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and Mir-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the transcriptional repressors of E-cadherin, ZEB1 and ZEB2. ZEB1 is also known to repress miR-200c-141 transcription in a negative feedback loop, but otherwise little is known about the transcriptional regulation of the miR-200 family and Mir-205. Recently, miR-200 silencing was also reported in cancer stem cells, implying that miR-200 deregulation is a key event in multiple levels of tumor biology. However, what prevents miR-200 expression remains largely unanswered. Here we report concerted transcriptional regulation of the miR-200 and Mir-205 loci in bladder tumors and bladder cell lines. Using a combination of miRNA expression arrays, qPCR assays and mass spectrometry DNA methylation analyses, we show that the miR-200 and Mir-205 loci are specifically silenced and gain promoter hypermethylation and repressive chromatin marks in muscle invasive bladder tumors and undifferentiated bladder cell lines. Moreover, we report that miR-200c expression is significantly correlated with early stage T1 bladder tumor progression, and propose miR-200 and Mir-205 silencing and DNA hypermethylation as possible prognostic markers in bladder cancer. In addition, we observe that the mesoderm transcription factor TWIST1 and miR-200 expression are inversely correlated in bladder tumor samples and cell lines. TWIST1 associates directly with the miR-200 and Mir-205 promoters, and may act as a repressor of miR-200 and Mir-205 expression.
Erik D Wiklund - One of the best experts on this subject based on the ideXlab platform.
-
epigenetic induced repression of microrna 205 is associated with med1 activation and a poorer prognosis in localized prostate cancer
Oncogene, 2013Co-Authors: Toby Hulf, Erik D Wiklund, Tennille Sibbritt, Kate I Patterson, Jenny Z Song, Clare Stirzaker, Shalima S Nair, Lisa G HorvathAbstract:Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (Mir-205) transcription is commonly repressed and the Mir-205 locus is hypermethylated. LOC642587, the Mir-205 host gene of unknown function, is also concordantly inactivated. We show that Mir-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of Mir-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the Mir-205 locus was strongly related with a decrease in Mir-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant Mir-205 DNA methylation in tumors compared with normal, and Mir-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that Mir-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.
-
coordinated epigenetic repression of the mir 200 family and mir 205 in invasive bladder cancer
International Journal of Cancer, 2011Co-Authors: Erik D Wiklund, Jesper B. Bramsen, Toby Hulf, Lars Dyrskjøt, Ramshanker Ramanathan, Thomas B. Hansen, Sune B. Villadsen, Shan Gao, Marie Stampe Ostenfeld, Michael BorreAbstract:MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and Mir-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the transcriptional repressors of E-cadherin, ZEB1 and ZEB2. ZEB1 is also known to repress miR-200c-141 transcription in a negative feedback loop, but otherwise little is known about the transcriptional regulation of the miR-200 family and Mir-205. Recently, miR-200 silencing was also reported in cancer stem cells, implying that miR-200 deregulation is a key event in multiple levels of tumor biology. However, what prevents miR-200 expression remains largely unanswered. Here we report concerted transcriptional regulation of the miR-200 and Mir-205 loci in bladder tumors and bladder cell lines. Using a combination of miRNA expression arrays, qPCR assays and mass spectrometry DNA methylation analyses, we show that the miR-200 and Mir-205 loci are specifically silenced and gain promoter hypermethylation and repressive chromatin marks in muscle invasive bladder tumors and undifferentiated bladder cell lines. Moreover, we report that miR-200c expression is significantly correlated with early stage T1 bladder tumor progression, and propose miR-200 and Mir-205 silencing and DNA hypermethylation as possible prognostic markers in bladder cancer. In addition, we observe that the mesoderm transcription factor TWIST1 and miR-200 expression are inversely correlated in bladder tumor samples and cell lines. TWIST1 associates directly with the miR-200 and Mir-205 promoters, and may act as a repressor of miR-200 and Mir-205 expression.
-
Coordinated epigenetic repression of the miR‐200 family and miR‐205 in invasive bladder cancer
International journal of cancer, 2011Co-Authors: Erik D Wiklund, Jesper B. Bramsen, Toby Hulf, Lars Dyrskjøt, Ramshanker Ramanathan, Thomas B. Hansen, Sune B. Villadsen, Shan Gao, Marie Stampe Ostenfeld, Michael BorreAbstract:MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and Mir-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the transcriptional repressors of E-cadherin, ZEB1 and ZEB2. ZEB1 is also known to repress miR-200c-141 transcription in a negative feedback loop, but otherwise little is known about the transcriptional regulation of the miR-200 family and Mir-205. Recently, miR-200 silencing was also reported in cancer stem cells, implying that miR-200 deregulation is a key event in multiple levels of tumor biology. However, what prevents miR-200 expression remains largely unanswered. Here we report concerted transcriptional regulation of the miR-200 and Mir-205 loci in bladder tumors and bladder cell lines. Using a combination of miRNA expression arrays, qPCR assays and mass spectrometry DNA methylation analyses, we show that the miR-200 and Mir-205 loci are specifically silenced and gain promoter hypermethylation and repressive chromatin marks in muscle invasive bladder tumors and undifferentiated bladder cell lines. Moreover, we report that miR-200c expression is significantly correlated with early stage T1 bladder tumor progression, and propose miR-200 and Mir-205 silencing and DNA hypermethylation as possible prognostic markers in bladder cancer. In addition, we observe that the mesoderm transcription factor TWIST1 and miR-200 expression are inversely correlated in bladder tumor samples and cell lines. TWIST1 associates directly with the miR-200 and Mir-205 promoters, and may act as a repressor of miR-200 and Mir-205 expression.
Toby Hulf - One of the best experts on this subject based on the ideXlab platform.
-
epigenetic induced repression of microrna 205 is associated with med1 activation and a poorer prognosis in localized prostate cancer
Oncogene, 2013Co-Authors: Toby Hulf, Erik D Wiklund, Tennille Sibbritt, Kate I Patterson, Jenny Z Song, Clare Stirzaker, Shalima S Nair, Lisa G HorvathAbstract:Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (Mir-205) transcription is commonly repressed and the Mir-205 locus is hypermethylated. LOC642587, the Mir-205 host gene of unknown function, is also concordantly inactivated. We show that Mir-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of Mir-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the Mir-205 locus was strongly related with a decrease in Mir-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant Mir-205 DNA methylation in tumors compared with normal, and Mir-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that Mir-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.
-
coordinated epigenetic repression of the mir 200 family and mir 205 in invasive bladder cancer
International Journal of Cancer, 2011Co-Authors: Erik D Wiklund, Jesper B. Bramsen, Toby Hulf, Lars Dyrskjøt, Ramshanker Ramanathan, Thomas B. Hansen, Sune B. Villadsen, Shan Gao, Marie Stampe Ostenfeld, Michael BorreAbstract:MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and Mir-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the transcriptional repressors of E-cadherin, ZEB1 and ZEB2. ZEB1 is also known to repress miR-200c-141 transcription in a negative feedback loop, but otherwise little is known about the transcriptional regulation of the miR-200 family and Mir-205. Recently, miR-200 silencing was also reported in cancer stem cells, implying that miR-200 deregulation is a key event in multiple levels of tumor biology. However, what prevents miR-200 expression remains largely unanswered. Here we report concerted transcriptional regulation of the miR-200 and Mir-205 loci in bladder tumors and bladder cell lines. Using a combination of miRNA expression arrays, qPCR assays and mass spectrometry DNA methylation analyses, we show that the miR-200 and Mir-205 loci are specifically silenced and gain promoter hypermethylation and repressive chromatin marks in muscle invasive bladder tumors and undifferentiated bladder cell lines. Moreover, we report that miR-200c expression is significantly correlated with early stage T1 bladder tumor progression, and propose miR-200 and Mir-205 silencing and DNA hypermethylation as possible prognostic markers in bladder cancer. In addition, we observe that the mesoderm transcription factor TWIST1 and miR-200 expression are inversely correlated in bladder tumor samples and cell lines. TWIST1 associates directly with the miR-200 and Mir-205 promoters, and may act as a repressor of miR-200 and Mir-205 expression.
-
Coordinated epigenetic repression of the miR‐200 family and miR‐205 in invasive bladder cancer
International journal of cancer, 2011Co-Authors: Erik D Wiklund, Jesper B. Bramsen, Toby Hulf, Lars Dyrskjøt, Ramshanker Ramanathan, Thomas B. Hansen, Sune B. Villadsen, Shan Gao, Marie Stampe Ostenfeld, Michael BorreAbstract:MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and Mir-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the transcriptional repressors of E-cadherin, ZEB1 and ZEB2. ZEB1 is also known to repress miR-200c-141 transcription in a negative feedback loop, but otherwise little is known about the transcriptional regulation of the miR-200 family and Mir-205. Recently, miR-200 silencing was also reported in cancer stem cells, implying that miR-200 deregulation is a key event in multiple levels of tumor biology. However, what prevents miR-200 expression remains largely unanswered. Here we report concerted transcriptional regulation of the miR-200 and Mir-205 loci in bladder tumors and bladder cell lines. Using a combination of miRNA expression arrays, qPCR assays and mass spectrometry DNA methylation analyses, we show that the miR-200 and Mir-205 loci are specifically silenced and gain promoter hypermethylation and repressive chromatin marks in muscle invasive bladder tumors and undifferentiated bladder cell lines. Moreover, we report that miR-200c expression is significantly correlated with early stage T1 bladder tumor progression, and propose miR-200 and Mir-205 silencing and DNA hypermethylation as possible prognostic markers in bladder cancer. In addition, we observe that the mesoderm transcription factor TWIST1 and miR-200 expression are inversely correlated in bladder tumor samples and cell lines. TWIST1 associates directly with the miR-200 and Mir-205 promoters, and may act as a repressor of miR-200 and Mir-205 expression.
Wei Zhang - One of the best experts on this subject based on the ideXlab platform.
-
Relative expressions of Mir-205-5p, Mir-205-3p, and miR-21 in tissues and serum of non-small cell lung cancer patients.
Molecular and cellular biochemistry, 2013Co-Authors: Min Jiang, Peng Zhang, Zuke Xiao, Ting Zhong, Fang Huang, Haibin Kuang, Wei ZhangAbstract:Objective was to assess and compare the relative expressions of Mir-205-5p, Mir-205-3p, and miR-21-3p in tissues and serum among non-small cell lung carcinoma (NSCLC) patients, benign pulmonary conditions patients, and healthy volunteers. Serum samples were obtained between October 2011 and September 2012 from 20 NSCLC patients undergoing surgical treatment, 20 patients diagnosed with a benign lung disease (pulmonary tuberculosis, pneumonia, chronic obstructive pulmonary disease, or interstitial pneumonia) (lesion group), and 20 healthy volunteers (control group). NSCLC patients provided cancer tissues and cancer-adjacent normal tissues during surgery (paired specimens). Quantitative RT-PCR was used to assess Mir-205-5p, Mir-205-3p, and miR-21-3p expressions in serum and tissue samples. The relative expressions of Mir-205-5p and Mir-205-3p were significantly higher in NSCLC tissues compared with cancer-adjacent paired specimens (both P < 0.001). In the serum, significantly higher Mir-205-5p, Mir-205-3p, and miR-21-3p relative expressions were observed in the NSCLC group compared with the two other groups (all P < 0.001). The relative expressions of Mir-205-5p and miR-21-3p in NSCLC tissues and serum were significantly correlated (r = 0.553, P = 0.011; and r = -0.541, P = 0.014, respectively), while no significant correlation was observed for Mir-205-3P (P = 0.120). Expressions of Mir-205-5p and Mir-205-3P in squamous cell carcinoma specimens were significantly higher than in lung adenocarcinoma specimens (both P = 0.001). Similarly, higher serum Mir-205-5p and Mir-205-3p levels were observed in squamous cell carcinoma patients (P = 0.033 and P = 0.002, respectively). In this preliminary and novel study, Mir-205-5p was more useful as a marker for NSCLC than Mir-205-3p or miR-21, indicating a potential for future applications in NSCLC diagnosis and prognosis.
Chengfeng Yang - One of the best experts on this subject based on the ideXlab platform.
-
Mir-205 Dysregulations in Breast Cancer: The Complexity and Opportunities.
Non-coding RNA, 2019Co-Authors: Yajuan Xiao, Brock Humphries, Chengfeng Yang, Zhishan WangAbstract:MicroRNAs (miRNAs) are endogenous non-coding small RNAs that downregulate target gene expression by imperfect base-pairing with the 3′ untranslated regions (3′UTRs) of target gene mRNAs. MiRNAs play important roles in regulating cancer cell proliferation, stemness maintenance, tumorigenesis, cancer metastasis, and cancer therapeutic resistance. While studies have shown that dysregulation of miRNA-205-5p (Mir-205) expression is controversial in different types of human cancers, it is generally observed that Mir-205-5p expression level is downregulated in breast cancer and that Mir-205-5p exhibits a tumor suppressive function in breast cancer. This review focuses on the role of Mir-205-5p dysregulation in different subtypes of breast cancer, with discussions on the effects of Mir-205-5p on breast cancer cell proliferation, epithelial–mesenchymal transition (EMT), metastasis, stemness and therapy-resistance, as well as genetic and epigenetic mechanisms that regulate Mir-205-5p expression in breast cancer. In addition, the potential diagnostic and therapeutic value of Mir-205-5p in breast cancer is also discussed. A comprehensive list of validated Mir-205-5p direct targets is presented. It is concluded that Mir-205-5p is an important tumor suppressive miRNA capable of inhibiting the growth and metastasis of human breast cancer, especially triple negative breast cancer. Mir-205-5p might be both a potential diagnostic biomarker and a therapeutic target for metastatic breast cancer.
-
Abstract 26: Mir-205 targets integrin-α5 and inhibits triple-negative breast cancer metastasis
Tumor Biology, 2018Co-Authors: Yajuan Xiao, Zhishan Wang, Hua Tao, Rongcheng Luo, Chengfeng YangAbstract:Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, lacking effective target therapy compared to ER/PR+ or HER2+ breast cancer. Micro-RNAs are small non-coding RNAs playing a significant role in cancer stemness maintenance, tumor growth, and metastasis. Studies showed that Mir-205 plays an important role in regulating EMT, cell proliferation and migration, tumor growth and metastasis, and drug-resistance of cancers, such as lung, renal, prostate and breast cancer. However, whether Mir-205 plays a role in TNBC tumor growth and metastasis remains to be determined. We found that higher Mir-205 expression level was strongly correlated with breast cancer patient better overall survival. The expression level of Mir-205 was prominently downregulated in basal mesenchymal-like highly migratory and invasive TNBC cell lines, compared to basal epithelial-like TNBC and other breast cancer cell lines. Bioinformatics analysis identified that integrin- α5 (ITGA5) is a potential target of Mir-205. Western blot analysis revealed that the expression level of integrin-α5 is significantly higher in basal mesenchymal-like TNBC cell lines than other breast cancer cell lines. Two Mir-205 overexpression cell lines were established by transfecting TNBC LM2 and SUM-159 cell lines with Mir-205 precursor expressing lentivirus. The expression level of ITGA5 was downregulated in Mir-205 overexpressing LM2 and SUM-159 cells. Wound healing assay and transwell cell migration assay revealed that Mir-205 overexpression reduced migration of TNBC cells, although no difference of cell proliferation was observed between Mir-205 overexpression and vectors control cells as determined by the MTT assay. The cancer stem cell-like property of TNBC cells was inhibited by Mir-205 overexpression as demonstrated by the mammary sphere formation assay. In in vivo experiments, mammary tumor growth and lung metastasis were inhibited by Mir-205 overexpression using mammary fat pad xenograft tumor models. When ITGA5 was re-expressed in Mir-205 overexpression cell lines, the migratory ability of TNBCs was rescued. The metastatic capability of TNBC mammary xenograft tumors was also restored. Further mechanistic studies proved that Mir-205 can reduce the formation of lamellipodium, a hallmark of Rac1/cdc42 activation and cell migration, by targeting ITGA5. Rac1/cdc42 pull-down assay showed that Mir-205 inhibited Rac1/cdc42 activation, while ITGA5 overexpression restored the activation of Rac1/cdc42. For uncovering the upstream regulator of Rac1/cdc42, several Rac inhibitors were scanned and it was found that inhibition of vav2 by EHop-016 reduced the downstream effects from ITGA5 signaling. CoIP revealed that Src/Vav2 pathway was activated by ITGA5. In conclusion, Mir-205 suppresses TNBC cell migration and tumor metastasis by targeting ITGA5 and inhibits Src/vav-2/Rac1/cdc42 pathway. Citation Format: Yajuan Xiao, Zhishan Wang, Yunfei Li, Jianjun Wu, Hua Tao, Aimin Li, Rongcheng Luo, Chengfeng Yang. Mir-205 targets integrin-α5 and inhibits triple-negative breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 26.