Dataset Information

Post-transcriptional Gene Regulation in Colitis Associated Cancer.

ABSTRACT: Colitis-associated cancer (CAC) has been linked to microRNA (miRNA) aberrant expression elicited by inflammation. In this study, we used the AOM/DSS-induced CAC mice model to explore the ectopic expression of miRNAs in the precancerous stage of CAC. As a result, we found that miR-31-5p, miR-223-3p, and let-7f-5p were dysregulated during the development of intestinal dysplasia. Subsequently, we first identified the role of these three miRNAs in CAC. Adenomatous polyposis coli (APC) was revealed as a new target of miR-223-3p, and solute carrier family 9- subfamily A-member 9 (SLC9A9) and APC membrane recruitment protein 3 (AMER3) were suggested as two new targets for let-7f-5p. For miR-31-5p, we proved that it can target LATS2 mRNA so as to modulate Hippo pathway in Caco2 cells. Second, to examine if targeting these three miRNAs would lead to CAC prevention, pedunculoside, a natural triterpene glycoside capable of rescuing the down-regulation of LATS2 and APC caused by either miR-31-5p or miR-223-3p overexpression, respectively, was used in the in vivo AOM/DSS-induced CAC model. The results showed that pedunculoside (25 mg/kg) substantially mitigated the damage to mice intestine caused by DSS/AOM. These results suggested that miRNAs-elicited post-transcriptional regulation is involved in the pathogenesis of CAC, and CAC can be prevented through targeting key miRNAs that are ectopically expressed in CAC.

SUBMITTER: Chen G

PROVIDER: S-EPMC6593052 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Post-transcriptional Gene Regulation in Colitis Associated Cancer.

Chen Gang G Feng Yuan Y Li Xuezheng X Jiang Zhe Z Bei Bei B Zhang Lin L Han Yueqing Y Li Yanwu Y Li Ning N

Frontiers in genetics 20190619

Colitis-associated cancer (CAC) has been linked to microRNA (miRNA) aberrant expression elicited by inflammation. In this study, we used the AOM/DSS-induced CAC mice model to explore the ectopic expression of miRNAs in the precancerous stage of CAC. As a result, we found that miR-31-5p, miR-223-3p, and let-7f-5p were dysregulated during the development of intestinal dysplasia. Subsequently, we first identified the role of these three miRNAs in CAC. Adenomatous polyposis coli (APC) was revealed a ...[more]

PMID: 31275360

Similar Datasets

Project description:BackgroundRheumatoid arthritis (RA) is an autoimmune disease characterised by systemic inflammation of joints. The observed complexity of RA pathogenesis and studies that have been carried out so far indicate that RA pathogenesis is regulated at multiple levels. Given the role of RNA editing in autoimmune disease, we hypothesised that RNA editing could contribute to RA pathogenesis by regulating gene expression through post-transcriptional mechanisms.MethodsWe identified RNA editing events in synovial tissues from early and established RA compared with normal subjects from an available transcriptome data set using REDItools. To investigate the potential effect of these RNA editing events on gene expression, we carried out an analysis of differential exon usage in the vicinity of the differentially edited sites using DEXSeq. We then used STRING to identify putative interactions between differentially edited genes identified from REDItools analysis. We also investigated the possible effects of these RNA editing events on miRNA-target mRNA interactions as predicted by miRanda.ResultsOur analysis revealed that there is extensive RNA editing in RA, with 304 and 273 differentially edited events in early RA and established RA, respectively. Of these, 25 sites were within 11 genes in early RA, and 34 sites were within 7 genes in established RA. DEXSeq analysis revealed that RNA editing correlated with differential exon usage in 4 differentially edited genes that have previously also been associated with RA in some measure: ATM, ZEB1, ANXA4, and TIMP3. DEXSeq analysis also revealed enrichment of some non-functional isoforms of these genes, perhaps at the expense of their full-length counterparts. Network analysis using STRING showed that several edited genes were part of the p53 protein-protein interaction network. We also identified several putative miRNA binding sites in the differentially edited genes that were lost upon editing.ConclusionsOur results suggested that the expression of genes involved in DNA repair and cell cycle, including ATM and ZEB1 which are well-known functional regulators of the DNA damage response pathway, could be regulated by RNA editing in RA synovia. This may contribute to an impaired DNA damage response in synovial tissues.

Project description:?-Synuclein is a member of the synucleins family of small proteins, which consists of three members:?, ?- and ?-synuclein. ?-Synuclein is abnormally expressed in a high percentage of advanced and metastatic tumors, but not in normal or benign tissues. Furthermore, ?-synuclein expression is strongly correlated with disease progression, and can stimulate proliferation, induce invasion and metastasis of cancer cells. ?-Synuclein transcription is regulated basically through the binding of AP-1 to specific sequences in intron 1. Here we show that ?-synuclein expression may be also regulated by micro RNAs (miRs) on post-transcriptional level. According to prediction by several methods, the 3'-untranslated region (UTR) of ?-synuclein gene contains targets for miRs. Insertion of ?-synuclein 3'-UTR downstream of the reporter luciferase (LUC) gene causes a 51% reduction of LUC activity after transfection into SKBR3 and Y79 cells, confirming the presence of efficient targets for miRs in this fragment. Expression of miR-4437 and miR-4674 for which putative targets in 3'-UTR were predicted caused a 61.2% and 60.1% reduction of endogenous ?-synuclein expression confirming their role in gene expression regulation. On the other hand, in cells overexpressing ?-synuclein no significant effect of miRs on ?-synuclein expression was found suggesting that miRs exert their regulatory effect only at low or moderate, but not at high level of ?-synuclein expression. Elevated level of ?-synuclein differentially changes the level of several miRs expression, upregulating the level of some miRs and downregulating the level of others. Three miRs upregulated as a result of ?-synuclein overexpression, i.e., miR-885-3p, miR-138 and miR-497 have putative targets in 3'-UTR of the ?-synuclein gene. Some of miRs differentially regulated by ?-synuclein may modulate signaling pathways and cancer related gene expression. This study demonstrates that miRs might provide cell-specific regulation of ?-synuclein expression and set the stage to further evaluate their role in pathophysiological processes.

Dataset Information

Post-transcriptional Gene Regulation in Colitis Associated Cancer.

Publications

Post-transcriptional Gene Regulation in Colitis Associated Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets