Role of miR‐203 in estrogen receptor‐mediated signaling in the rat uterus and endometrial carcinoma

Zierau, Oliver; Helle, Janina; Schadyew, Sabina; Morgenroth, Yanni; Bentler, Martin; Hennig, Alexander; Chittur, Sridar V.; Tenniswood, Martin; Kretzschmar, Georg

doi:10.1002/jcb.26675

Cited by 25 publications

(16 citation statements)

References 44 publications

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“…Thereby, the protective effect of rs1536309 might be more easily observed in older patients. In a recent study, the upregulated miR-146b-5p was found correlated with E2 expression (20). Thus, the influence of this SNP site might be attenuated in female due to the higher level of miR-146b-5p.…”

Section: Discussionmentioning

confidence: 90%

A Genetic Variant Located in miR-146b Promoter Region Is Associated with Prognosis of Gastric Cancer

Wang

et al. 2018

Cancer Epidemiology, Biomarkers &Amp; Prevention

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SNPs in the promoter region of miRNAs have been reported to be associated with cancer prognosis. Our previous study found that miR-146b had a strong correlation with the stage classification of gastric cancer and contributed to tumor progression. The current study was aimed at investigating whether an SNP located in the promoter region of could affect the survival rate of gastric cancer. Using bioinformatics tools, we identified one SNP (rs1536309) that is located in the promoter. We genotyped this SNP site to assess its association with gastric cancer prognosis in 940 cases. We found that the dominant model of rs1536309 was associated with a higher survival rate of gastric cancer. The association remained significant in the subgroup analysis by age (≤60), sex (male), tumor size (≤5 cm), histologic type (diffuse), lymph node metastasis (N0), distant metastasis (M0), and TNM stage (I/II). Our results suggested that the rs1536309 polymorphism may be a potential biomarker for the prognosis of gastric cancer. This is the first evidence showing that patients carrying the rs1536309 CC/CT genotypes exhibited better survival than those carrying the TT genotype, suggesting the protective effect of the C allele in the prognosis of gastric cancer..

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Section: Discussionmentioning

confidence: 90%

A Genetic Variant Located in miR-146b Promoter Region Is Associated with Prognosis of Gastric Cancer

Wang

et al. 2018

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The two networks closely communicating each other by sharing a few common genes. For example, NFAT5 is regulated by an estrogen-induced microRNA [37] and the regulation is mediated via PI3K/AKT-signaling pathways [38]. In addition, A100A9, a calcium-binding protein that is highly expressed in malignant breast cancer, induces a decrease of ERα in MCF-7 cell [35], and inhibits PI3K/AKT pathway in pancreatic adenocarcinoma cells [39].…”

Section: Discussionmentioning

confidence: 99%

ELOVL2: a novel tumor suppressor attenuating tamoxifen resistance in breast cancer

Jeong

Ham

Kim

et al. 2020

Preprint

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Background To comprehensively understand the molecular mechanism of tamoxifen resistance (TamR) acquisition by epigenetically regulated genes, it is essential to identify pivotal genes by genome-wide methylation analysis and verify their function in xenograft animal model and cancer patients. Methods The MCF-7/TamR breast cancer cell line was developed and a genome-wide methylation array was performed. The methylation and expression of ELOVL2 was validated in cultured cells, xenografted tumor tissue, and breast cancer patients by methylation-specific PCR, qRT-PCR, Western blot analysis, and immunohistochemistry. Deregulation of ELOVL2 and THEM4 was achieved using siRNA or generating stable transfectants. Tam sensitivity, cell growth, and apoptosis were monitored by colorimetric and colony formation assay and flow cytometric analysis. Pathway analysis was performed to generate networks for the differentially methylated genes in the MCF-7/TamR cells and for the differentially expressed genes in the ELOVL2-overexpressing cells. Results Genome-wide methylation analysis in the MCF-7/TamR cells identified elongation of very-long chain fatty acid protein 2 (ELOVL2) to be significantly hypermethylated and downregulated, which was further verified in the tumor tissues from TamR breast cancer patients (n = 28) compared with those from Tam-sensitive (TamS) patients (n = 33) (P < 0.001). Immunohistochemical analysis of tissues from cancer patients showed lower expression of ELOVL2 in the TamR than TamS tissues. Growth of the MCF-7/TamR cells overexpressing ELOVL2 was retarded in cell culture and also in xenograft tumor tissue. Strikingly, ELOVL2 attenuated resistance to Tam up to 70% judged by the colorimetric and colony formation assay and xenograft mouse model. ELOVL2 contributed to the recovery of Tam sensitivity by regulating a group of genes in the AKT and ERα signaling pathways, e.g., THEM4, which plays crucial roles in drug resistance. Conclusions ELOVL2 was hypermethylated and downregulated in TamR breast cancer patients compared with TamS patients. ELOVL2 is responsible for the recovery of Tam sensitivity. AKT- and ERα-hubbed networks are pivotal in ELOVL2 signaling, where THEM4 contributes to the relaying ELOVL2 signaling. This study implies that deregulation of a gene in fatty acid metabolism can lead to drug resistance, giving insight into the development of a new therapeutic strategy for drug-resistant breast cancer.

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“…Pathological changes in these genes can cause anomalistic transduction of signal pathways such as AKT‐/‐PI3K, NF‐κB, MARK, and Wnt‐/‐β‐catenin, or abnormal expression of P53 and P16 proteins, leading to uncontrolled cell proliferation and tumorigenesis. Given its extensive study in tumors and obvious therapeutic effect, the CRISPR‐Cas9 technology has been used in related research and treatment of endometrial cancer (summarized in Table ).…”

Section: Endometrial Cancer and Crispr‐cas9mentioning

confidence: 99%

“…SDPR gene depletion by CRISPR‐Cas9 in HEC‐1B and HEC‐108 cells can suppress tumor cell migration, invasion and EMT by inhibiting the ILK‐/‐ALDH1 pathway . Knockout of MIR‐203 in RUCA‐1 cells caused tumor cells to stagnate in the G2 phase of the cell cycle and cell viability also decreased . In short, because endometrial cancer is a multigene regulatory disease, many specific mechanisms are still unclear.…”

Section: Endometrial Cancer and Crispr‐cas9mentioning

confidence: 99%

Applications of CRISPR‐Cas9 in gynecological cancer research

et al. 2020

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Gynecological cancers pose a significant threat to women's health worldwide, with cervical cancer, ovarian cancer, and endometrial cancer having high incidences.Current gynecological cancer treatment methods mainly include surgery, chemotherapy, radiotherapy, and chemoradiotherapy. The CRISPR-Cas9 gene editing technology as a new therapeutic method has shown tremendous effect in the treatment of other cancers, promoting research on its potential therapeutic effect in gynecological cancer. In this article, we reviewed the current research status of CRISPR-Cas9 technology in gynecological cancer, focusing on the importance of studying the mechanism of CRISPR-Cas9 in gynecological cancer treatment, thereby laying a foundation for further research on its clinical application. K E Y W O R D S cancer treatment, CRISPR-Cas9, gene editing, gynecological cancers 1 | INTRODUCTIONThe CRISPR sequence, a cluster of regularly spaced short palindromic repeats, is a special ordered repeating sequence found in the genome of Escherichia coli. The CRISPR-Cas9 system constitutes the acquired immune system of E. coli. 1 In 2012, scientists discovered that the CRISPR-Cas9 system can produce mature CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA), which form a composite structure and have a directional guidance function to guide Cas9 to specific DNA sequences, resulting in DNA double-strand breaks. 2 By 2013, scientists had successfully edited the genome of eukaryotic cells using the CRISPR-Cas9 system. [3][4][5] Since then, the CRISPR-Cas9 gene editing technology has dramatically impacted the field of life sciences and has become one of the most significant research areas at present. The working principle of the CRISPR-Cas9 system is to artificially design two kinds of RNA: crRNA and tracrRNA, and then transform them into a single guide RNA (sgRNA), thereby guiding Cas9 to cut DNA in a targeted manner, following which cells are able to delete the target DNA through homologous and non-homologous DNA damage repair mechanisms. 6 Compared with traditional gene editing tools, such as ZFN and TALEN, the CRISPR-Cas9 technology has the advantages of simple design, ability to target any DNA sequence in the cell and to target multiple targets simultaneously, higher cutting efficiency, and lower cost. 7 At present, the CRISPR-Cas9 gene editing technology has contributed to great advancements in the clinical treatment of diseases. Major breakthroughs have been achieved in treating hereditary diseases using this technology. [8][9][10] It was used to knock out the beta-globin gene, the pathogenic gene of β-hemoglobinopathy, and it also employed rAAV6, as a donor template, to effectively correct the disease-causing mutation of SCD through homologous recombination. 10 In addition, The CRISPR-Cas9 gene editing technology has been widely used treatment-related researches and in the establishment of disease model of many cancers, including pancreatic, lung, gastric, colon, kidney, liver, head and neck, and skin cancers. [11][12][13][14][15][16][...

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Role of miR‐203 in estrogen receptor‐mediated signaling in the rat uterus and endometrial carcinoma

Cited by 25 publications

References 44 publications

A Genetic Variant Located in miR-146b Promoter Region Is Associated with Prognosis of Gastric Cancer

A Genetic Variant Located in miR-146b Promoter Region Is Associated with Prognosis of Gastric Cancer

ELOVL2: a novel tumor suppressor attenuating tamoxifen resistance in breast cancer

Applications of CRISPR‐Cas9 in gynecological cancer research

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