Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MicroRNA-30c (miR-30c) has been reported to be a tumour suppressor in endometrial cancer (EC). We demonstrate that miR-30c is down-regulated in EC tissue and is highly expressed in estrogen receptor (ER)-negative HEC-1-B cells. MiR-30c directly inhibits MTA-1 expression and functions as a tumour suppressor via the miR-30c-MTA-1 signalling pathway. Furthermore, miR-30c is decreased upon E2 treatment in both ER-positive Ishikawa and ER-negative HEC-1-B cells. Taken together, our results suggest that miR-30c is an important deregulated miRNA in EC and might serve as a potential biomarker and novel therapeutic target for EC.
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PMID:Estrogen regulates the tumour suppressor MiRNA-30c and its target gene, MTA-1, in endometrial cancer. 2459 16

Recent studies have identified FAT tumour suppressor homologue 4 (FAT4), an essential component of adherents junctions, involved in several cancers. However, its role in endometrial cancer (EC) remains unclear. In this study, we first analyzed the association between FAT4 expression and tumour stage, tumour type, and patient prognosis in 552 tumour samples and 35 non-tumour samples from The Cancer Genome Atlas (TCGA) database. The association of decreased FAT4 expression with advanced signature (lymph node metastasis, lymphovascular invasion and muscular infiltration) in EC patients was also confirmed by our own dataset. Stable FAT4 Knockdown promoted EC cell lines proliferation and invasion. FAT4 overexpression inhibited the parental cell phenotype. FAT4 silencing resulted in decreased phosphorylation of the LATS1/2 and YAP while increased YAP nuclear translocation which was associated with the promotion of proliferation and invasion. PCR array analysis of the negative control and shFAT4 HEC-1B cell lines revealed that the deubiquitinating enzyme USP51 was a FAT4 interacting target gene. Ablating USP51 by shRNA decreased cellular FAT4 protein level while overexpression of USP51 increased FAT4 protein level. Coimmunoprecipitation confirmed the direct binding of FAT4 and USP51 which was essential for FAT4's function in EC. The growth inhibitory effect of FAT4 was also attenuated by USP51 down-regulation. In conclusion, suppression of FAT4 by inactivation of deubiquitinating enzyme USP51 promoted proliferation and invasion of EC cells via inhibiting Hippo pathway.
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PMID:FAT4-USP51 complex regulates the proliferation and invasion of endometrial cancer via Hippo pathway. 3121 54

Endometrial cancer (EC) is a common gynecological malignancy with relatively favourable prognosis, although alternative diagnostic and therapeutic options remain to be explored for advanced disease. Recent studies enabled to apply microRNAs (miRs) to clinical cancer management as promising diagnostic and therapeutic biomarkers. We here aimed to identify proliferation-associated miRNAs and characterize their functions in EC cells. Our small RNA-sequencing analysis showed that miR-191 is abundantly expressed in HEC-1A and Ishikawa EC cells along with the high expression of miR-182, which was previously characterized as an EC proliferation-related miRNA in EC. We showed that miR-191 was upregulated in EC tissues than in adjacent normal tissues and its knockdown repressed EC cell proliferation. In silico miRNA target screening identified that ten-eleven translocation 1 (TET1) is one of the putative miR-191 targets. TET1 expression could be downregulated by miR-191 through the mRNA-miRNA interaction in the 3'-untranslated region of TET1. In line with TET1 functions as a methylcytosine dioxygenase, which removes genome-wide DNA methylation marks, decreased TET1 expression resulted in hypermethylation in the promotor region of tumour suppressor adenomatous polyposis coli. Taken together, miR-191 could function as an oncogenic miRNA in EC and serve as a prospective diagnostic and therapeutic target for advanced disease.
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PMID:MicroRNA-191 regulates endometrial cancer cell growth via TET1-mediated epigenetic modulation of APC. 3200 27