&lt;p&gt;The SP1-Induced Long Noncoding RNA, LINC00339, Promotes Tumorigenesis in Colorectal Cancer via the miR-378a-3p/MED19 Axis&lt;/p&gt;

Ye, Hua; Li, Wende; Wu, Kefeng; Liu, Yi; Lv, Yingnian; Zhu, Ye; Luo, Hui; Liao, Chen Zi

doi:10.2147/ott.s277254

Cited by 21 publications

(25 citation statements)

References 31 publications

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“…The association on chromosome 1 appears to be novel in the context of cervical pathology, although the region is a known risk locus for other gynecological problems, such as endometriosis, uterine fibroids, and ovarian cancer. Our results support LINC00339 and CDC42/CDC42-AS1 as the most likely candidate genes in this locus, which is in line with evidence from other cancers (32)(33)(34)(35). In fact, previous studies have shown that knocking down LINC00339 expression leads to increased CDC42 expression (48), which is supported by data from eQTLsvariants associated with increased expression of LINC00339 have an opposite effect on CDC42 expression (49).…”

Section: Discussionsupporting

confidence: 90%

“…CDC42-AS1 and LINC00339 were also mapped by colocalisation signal in relevant tissue (Figure 1 , Supplementary Figure 3). LINC00339 has a known role in promoting the proliferation of several cancers (32)(33)(34), while there is also evidence to link CDC42 expression with cervical cancer invasion and migration (35). The region has been previously associated with uterine fibroids, endometriosis, endometrial cancer (36), epithelial ovarian cancer, gestational age, and bone mineral density (Supplementary Table 7).…”

Section: Gwas Meta-analysis For Cervical Cancermentioning

confidence: 99%

“…Of the other credible set variants, rs3768579 and rs3754496 are located in transcription start site (TSS) flanking regions of LINC00339 and CDC42 in HeLa cells, while rs72665317 and rs10917128 overlap with enhancer marks (Supplementary Table 6, Supplementary Figure 6). LINC00339 has a known role in promoting the proliferation of several cancers [33][34][35] , while there is also evidence to link CDC42 expression with cervical cancer invasion and migration 36 . The region has been previously associated with uterine fibroids, endometriosis, endometrial cancer 37 , epithelial ovarian cancer, gestational age, and bone mineral density (Supplementary Table 7).…”

Section: Gwas Meta-analyses For Cervical Ectropion Cervicitis and Dys...mentioning

confidence: 99%

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GWAS meta-analysis and gene expression data link reproductive tract development, immune response and cellular proliferation/apoptosis with cervical cancer and clarify overlap with other cervical phenotypes

Koel

Võsa

Lepamets

et al. 2021

Preprint

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Background The uterine cervix has an important role in female reproductive health, but not much is known about the genetic determinants of cervical biology and pathology. Genome-wide association studies (GWAS) with increasing sample sizes have reported a few genetic associations for cervical cancer. However, GWAS is only the first step in mapping the genetic susceptibility and thus, the underlying biology in cervical cancer and other cervical phenotypes is still not entirely understood. Here, we use data from large biobanks to characterise the genetics of cervical phenotypes (including cervical cancer) and leverage latest computational methods and gene expression data to refine the association signals for cervical cancer. Methods Using Estonian Biobank and FinnGen data, we characterise the genetic signals associated with cervical ectropion (10,162 cases/151,347 controls), cervicitis (19,285/185,708) and cervical dysplasia (14,694/150,563). We present the results from the largest trans-ethnic GWAS meta-analysis of cervical cancer, including up to 9,229 cases and 490,304 controls from Estonian Biobank, the FinnGen study, the UK Biobank and Biobank Japan. We combine GWAS results with gene expression data and chromatin regulatory annotations in HeLa cervical carcinoma cells to propose the most likely candidate genes and causal variants for every locus associated with cervical cancer. We further dissect the HLA association with cervical pathology using imputed data on alleles and amino acid polymorphisms. Results We report a single associated locus on 2q13 for both cervical ectropion (rs3748916, p=5.1 x 10-16) and cervicitis (rs1049137, p=3.9 x 10-10), and five signals for cervical dysplasia - 6p21.32 (rs1053726, p=9.1 x 10-9; rs36214159, 1.6 x 10-22), 2q24.1 (rs12611652, p=3.2 x 10-9) near DAPL1, 2q13 ns1049137, p=6.4 x 10-9) near PAX8, and 5p15.33 (rs6866294, p=2.1 x 10-9), downstream of CLPTM1L. We identify five loci associated with cervical cancer in the trans-ethnic meta-analysis: 1p36.12 (rs2268177, p= 3.1 x 10-8), 2q13 (rs4849177, p=9.4 x 10-15), 5p15.33 (rs27069, p=1.3 x 10-14), 17q12 (rs12603332, p=1.2 x 10-9), and 6p21.32 (rs35508382, p=1.0 x 10-39). Joint analysis of dysplasia and cancer datasets revealed an association on chromosome 19 (rs425787, p=3.5 x 10-8), near CD70. Conclusions Our results map PAX8/PAX8-AS1, LINC00339, CDC42, CLPTM1L, HLA-DRB1, HLA-B, and GSDMB as the most likely candidate genes for cervical cancer, which provides novel insight into cervical cancer pathogenesis and supports the role of genes involved in reproductive tract development, immune response and cellular proliferation/apoptosis. We further show that PAX8/PAX8-AS1 has a central role in cervical biology and pathology, as it was associated with all analysed phenotypes. The detailed characterisation of association signals, together with mapping of causal variants and genes offers valuable leads for further functional studies.

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Section: Discussionsupporting

confidence: 90%

Section: Gwas Meta-analysis For Cervical Cancermentioning

confidence: 99%

Section: Gwas Meta-analyses For Cervical Ectropion Cervicitis and Dys...mentioning

confidence: 99%

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GWAS meta-analysis and gene expression data link reproductive tract development, immune response and cellular proliferation/apoptosis with cervical cancer and clarify overlap with other cervical phenotypes

Koel

Võsa

Lepamets

et al. 2021

Preprint

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“…HOXB2 is related to the invasion and proliferation of glioma cells in vitro, and has a certain effect on the invasion of glioma cells (5). We examined the regulatory role of the SP1/LINC00339/miR-378a-3p/ MED19 axis in colorectal cancer, and provided new insights into the molecular mechanism of colorectal cancer (6). An in vivo clustered regularly interspaced short palindromic repeats (CRISPR) screening showed that protein tyrosine phosphatase, non-receptor type 2 (PTPN2) deletion in tumor cells enhances the effect of immunotherapy by enhancing the antigen presentation and growth inhibition mediated by interferon-γ.…”

Section: Introductionmentioning

confidence: 99%

Identification of potential biomarkers in ovarian carcinoma and an evaluation of their prognostic value

Cai¹,

Qiu²,

Wang³

et al. 2021

Ann Transl Med

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Background: Ovarian cancer is one of the most common malignant tumors in female genital organs, and its incidence rate is high. However, the pathogenesis and prognostic markers of ovarian cancer are unclear.This study sought to screen potential markers of ovarian cancer and to explore their prognostic value.Methods: The Cancer Genome Atlas, Gene Expression Omnibus, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used in this study. The least absolute shrinkage and selection operator (LASSO), multivariate Cox regression and stepwise regression analysis were chosen to screen genes and construct risk model. Gene Set Enrichment Analysis (GSEA) and an immune-infiltration analysis were performed.Results: One hundred thirty two co-expressed genes were found. They involved in metabolism, protein phosphorylation, mitochondria, and immune signaling pathways. Twelve genes significantly related to the survival of ovarian cancer were identified. Eight risk genes (i.e., CACNB1, FAM120B, HOXB2, MED19, PTPN2, SMU1, WAC.AS1, and BCL2L11) were further screened and used to construct the risk model. The risk status might be an independent prognostic factor of ovarian cancer, and most of the biological functions of genes expressed in high-risk ovarian cancer were related to synapse, adhesion, and immune-related functions. The clusters of CD4+ T cells and M2 macrophages were high in high-risk status samples.Conclusions: In ovarian cancer, the abnormal expression of 8 genes, including CACNB1, FAM120B, HOXB2, MED19, PTPN2, SMU1, WAC.AS1, and BCL2L11, is closely related to ovarian cancer progression, and these genes can serve as independent prognosis markers of ovarian cancer.

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“…17 For prostate cancer cells, the downregulation of MED19 inhibited the proliferation, migration, and invasion cancer cells, as well as the expression of EMT-related genes, such as P27, E-cadherin, N-cadherin, Vimentin, Snail1 , and Snail2. 28 Recent studies have found that MED19 promotes the EMT process by activating the activity of WNT/β-catenin signaling pathway, thus inhibiting the proliferation and migration of colorectal cancer cells, 29 which is of great significance in exploring the influence of MED19 on tumorigenesis and metastasis.…”

Section: Effect Of Med19 On Invasion and Migration Of Tumor Cellmentioning

confidence: 99%

The role of mediator complex subunit 19 in human diseases

Zhang

Qin

Yan

et al. 2021

Exp Biol Med (Maywood)

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Mediator is an evolutionarily conserved multi-protein complex that mediates the interaction between different proteins as a basic linker in the transcription mechanism of eukaryotes. It interacts with RNA polymerase II and participates in the process of gene expression. Mediator complex subunit 19 or regulation by oxygen 3, or lung cancer metastasis-related protein 1 is located at the head of the mediator complex; it is a multi-protein co-activator that induces the transcription of RNA polymerase II by DNA transcription factors. It is a tumor-related gene that plays an important role in transcriptional regulation, cell proliferation, and apoptosis and is closely related to the occurrence and development of the cancers of the lung, bladder, skin, etc. Here, we used the structure of mediator complex subunit 19 to review its role in tumor progression, fat metabolism, drug therapy, as well as the novel coronavirus, which has attracted much attention at present, suggesting that mediator complex subunit 19 has broad application in the occurrence and development of clinical diseases. As a tumor-related gene, the role and mechanism of mediator complex subunit 19 in the regulation of tumor growth could be of great significance for the diagnosis, prognosis, and treatment of mediator complex subunit 19 -related tumors.

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<p>The SP1-Induced Long Noncoding RNA, LINC00339, Promotes Tumorigenesis in Colorectal Cancer via the miR-378a-3p/MED19 Axis</p>

Cited by 21 publications

References 31 publications

GWAS meta-analysis and gene expression data link reproductive tract development, immune response and cellular proliferation/apoptosis with cervical cancer and clarify overlap with other cervical phenotypes

GWAS meta-analysis and gene expression data link reproductive tract development, immune response and cellular proliferation/apoptosis with cervical cancer and clarify overlap with other cervical phenotypes

Identification of potential biomarkers in ovarian carcinoma and an evaluation of their prognostic value

The role of mediator complex subunit 19 in human diseases

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