MAGI2‐AS3 rs7783388 polymorphism contributes to colorectal cancer risk through altering the binding affinity of the transcription factor GR to the MAGI2‐AS3 promoter

Yang, Xi; Wu, Shenshen; Li, Xiaobo; Yin, Ying; Chen, Rui

doi:10.1002/jcla.23431

Cited by 15 publications

(7 citation statements)

References 43 publications

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“…Long non‐coding RNAs (lncRNAs) are an important class of ncRNAs that have a huge impact on the cancer progress. These RNAs are transcribed by RNA polymerase II, with a length of 200 nt or more, from different regions of the genome, including intronic and intergenic sites 5,6 . Considering this point, it has been inferred that lncRNA transcription usually does not depend on the presence of the open reading frames and it has been estimated that the human genome contains more than 15 000 lncRNAs‐related genes that could produce over 23 000 functional lncRNAs 7 .…”

Section: Introductionmentioning

confidence: 99%

Identification of a stool long non‐coding RNAs panel as a potential biomarker for early detection of colorectal cancer

Gharib

Nazemalhosseini‐Mojarad

Baghdar

et al. 2020

Clinical Laboratory Analysis

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Background The feces of colorectal cancer (CRC) patients contain tumor colonocytes, which constantly shed into the lumen area. Therefore, stool evaluation can be considered as a rapid and low‐risk way to directly determine the colon and rectum status. As long non‐coding RNAs (lncRNAs) alterations are important in cancer cells fate regulation, we aimed to assess the level of a panel of cancer‐related lncRNAs in fecal colonocytes. Methods The population study consisted of 150 subjects, including a training set, a validation set, and a group of 30 colon polyps. The expression levels of lncRNAs were evaluated by quantitative real‐time PCR (qRT‐PCR). The NPInetr and EnrichR tools were used to identify the interactions and functions of lncRNAs. Results A total of 10 significantly dysregulated lncRNAs, including CCAT1, CCAT2, H19, HOTAIR, HULC, MALAT1, PCAT1, MEG3, PTENP1, and TUSC7, were chosen for designing a predictive panel. The diagnostic performance of the panel in distinguishing CRCs from the healthy group was AUC: 0.8554 in the training set and 0.8465 in the validation set. The AUC for early CRCs (I‐II TNM stages) was 0.8554 in the training set and 0.8465 in the validation set, and for advanced CRCs (III‐IV TNM stages) were 0.9281 in the training set and 0.9236 in the validation set. The corresponding AUC for CRCs vs polyps were 0.9228 (I‐IV TNM stages), 0.9042 (I‐II TNM stages), and 0.9362 (III‐IV TNM stages). Conclusions These data represented the application of analysis of fecal colonocytes lncRNAs in early detection of CRC.

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Section: Introductionmentioning

confidence: 99%

Identification of a stool long non‐coding RNAs panel as a potential biomarker for early detection of colorectal cancer

Gharib

Nazemalhosseini‐Mojarad

Baghdar

et al. 2020

Clinical Laboratory Analysis

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“…All these studies report the downregulation of MAGI2-AS3 during carcinogenesis and support a role of this lncRNA as a tumor suppressor in adrenal, brain, breast, bladder, liver, lung, colorectal, prostate, pancreatic, ovarian, and renal cancers [ 208 , 209 , 210 , 213 , 214 , 217 , 220 , 222 , 223 , 230 , 232 , 234 , 235 , 236 , 237 , 238 , 239 ].…”

Section: Magi Cernas In Carcinogenesismentioning

confidence: 80%

“…A polymorphism in MAGI2-AS3 (rs7783388 GG genotype) seems to enhance colorectal cancer risk as a result of decreased binding affinity of glucocorticoid receptor to the MAGI2-AS3 promoter, leading to lower MAGI2-AS3 accumulation [ 236 ]. In this connection, functional experiments showed that MAGI2-AS3 overexpression suppressed proliferation (cell cycle arrest at G0/G1 phase), decreased migration and invasiveness, and promoted apoptosis of the human colon cancer SW480 and SW620 cell lines [ 236 ]. In this cancer, a MAGI2-AS3 LncRNA-miRNA-mRNA network of differentially expressed genes has been recently proposed [ 237 ].…”

Section: Magi Cernas In Carcinogenesismentioning

confidence: 99%

A New Story of the Three Magi: Scaffolding Proteins and lncRNA Suppressors of Cancer

Kotelevets

Chastre

2021

Cancers

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Scaffolding molecules exert a critical role in orchestrating cellular response through the spatiotemporal assembly of effector proteins as signalosomes. By increasing the efficiency and selectivity of intracellular signaling, these molecules can exert (anti/pro)oncogenic activities. As an archetype of scaffolding proteins with tumor suppressor property, the present review focuses on MAGI1, 2, and 3 (membrane-associated guanylate kinase inverted), a subgroup of the MAGUK protein family, that mediate networks involving receptors, junctional complexes, signaling molecules, and the cytoskeleton. MAGI1, 2, and 3 are comprised of 6 PDZ domains, 2 WW domains, and 1 GUK domain. These 9 protein binding modules allow selective interactions with a wide range of effectors, including the PTEN tumor suppressor, the β-catenin and YAP1 proto-oncogenes, and the regulation of the PI3K/AKT, the Wnt, and the Hippo signaling pathways. The frequent downmodulation of MAGIs in various human malignancies makes these scaffolding molecules and their ligands putative therapeutic targets. Interestingly, MAGI1 and MAGI2 genetic loci generate a series of long non-coding RNAs that act as a tumor promoter or suppressor in a tissue-dependent manner, by selectively sponging some miRNAs or by regulating epigenetic processes. Here, we discuss the different paths followed by the three MAGIs to control carcinogenesis.

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“…Additional suggestive signals were located in the MAGI2 gene and downstream of the IL15 gene. The SNP rs34931968 detected in our cohort is located in the MAGI2 gene, upstream of a lncRNA that is next to MAGI2 (called MAGI2-AS3 ), a lncRNA that has been involved in CRC [ 54 , 55 , 56 ]. In addition, the SNP rs34931968 is in linkage disequilibrium with an SNP (rs7783388) involved in CRC throughout changes in MAGI2-AS3 expression [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…The SNP rs34931968 detected in our cohort is located in the MAGI2 gene, upstream of a lncRNA that is next to MAGI2 (called MAGI2-AS3 ), a lncRNA that has been involved in CRC [ 54 , 55 , 56 ]. In addition, the SNP rs34931968 is in linkage disequilibrium with an SNP (rs7783388) involved in CRC throughout changes in MAGI2-AS3 expression [ 56 ]. In the case of IL15 , its expression has been associated with the outcome of CRC [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Performance of the Use of Genetic Information to Assess the Risk of Colorectal Cancer in the Basque Population

Garcia-Etxebarria

Etxart

Barrero

et al. 2022

Cancers

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Although the genetic contribution to colorectal cancer (CRC) has been studied in various populations, studies on the applicability of available genetic information in the Basque population are scarce. In total, 835 CRC cases and 940 controls from the Basque population were genotyped and genome-wide association studies were carried out. Mendelian Randomization analyses were used to discover the effect of modifiable risk factors and microbiota on CRC. In total, 25 polygenic risk score models were evaluated to assess their performance in CRC risk calculation. Moreover, 492 inflammatory bowel disease cases were used to assess whether that genetic information would not confuse both conditions. Five suggestive (p < 5 × 10−6) loci were associated with CRC risk, where genes previously associated with CRC were located (e.g., ABCA12, ATIC or ERBB4). Moreover, the analyses of CRC locations detected additional genes consistent with the biology of CRC. The possible contribution of cholesterol, BMI, Firmicutes and Cyanobacteria to CRC risk was detected by Mendelian Randomization. Finally, although polygenic risk score models showed variable performance, the best model performed correctly regardless of the location and did not misclassify inflammatory bowel disease cases. Our results are consistent with CRC biology and genetic risk models and could be applied to assess CRC risk in the Basque population.

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MAGI2‐AS3 rs7783388 polymorphism contributes to colorectal cancer risk through altering the binding affinity of the transcription factor GR to the MAGI2‐AS3 promoter

Cited by 15 publications

References 43 publications

Identification of a stool long non‐coding RNAs panel as a potential biomarker for early detection of colorectal cancer

Identification of a stool long non‐coding RNAs panel as a potential biomarker for early detection of colorectal cancer

A New Story of the Three Magi: Scaffolding Proteins and lncRNA Suppressors of Cancer

Performance of the Use of Genetic Information to Assess the Risk of Colorectal Cancer in the Basque Population

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