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Role of differentially expressed microRNA-139-5p in the regulation of phenotypic internal anal sphincter smooth muscle tone

ABSTRACT: The present study focused on establishing the role of microRNA-139-5p (miRNA-139-5p) in the phenotypic expression of basal tone in rat internal anal sphincter (IAS) vs. lack of tone in truly phasic smooth muscle of anococcygeus (ASM), via RhoA-associated kinase (RhoA/ROCK2).

ORGANISM(S): synthetic construct Rattus norvegicus

PROVIDER: GSE90981 | GEO | 2017/06/12

SECONDARY ACCESSION(S): PRJNA356547

REPOSITORIES: GEO

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Title: Aging-associated changes in microRNA expression profile of internal anal sphincter smooth muscle: Role of microRNA-133a

Project description:A comprehensive –omic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of IAS smooth muscle contractile phenotype and basal tone. MicroRNA profiling, genome wide expression, validation and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a and rno-miR-206 were found to be up-regulated in aging IAS. qRT-PCR confirmed the up-regulated expression of these miRNAs and down regulation of multiple, predicted targets (Eln, Col3a1, Col1a1, Zeb2, Myocd, SRF, Smad1, Smad2, RhoA/ROCK2, Fn1, Sm22-v2, Klf4, and Acta2) involved in regulation of SM contractility. Subsequent studies demonstrated an aging-associated increase in the expression of miR-133a, corresponding decreases in RhoA, ROCK2, MYOCD, SRF and SM22α protein expression, RhoA-signaling, and a decrease in basal and agonist (U-46619 (thromboxane A2 analog))-induced increase in the IAS tone. Moreover, in vitro transfection of miR-133a caused a dose-dependent increase of IAS tone in strips, which was reversed by anti-miR-133a. Lastly, in vivo perianal injection of anti-miR-133a reversed the loss of IAS tone associated with age. This work establishes the important regulatory effect of miRNA-133a on basal and agonist-stimulated IAS tone. Moreover, reversal of age-associated loss of tone via anti-miR delivery strongly implicates miR dysregulation as a causal factor in the aging-associated decrease in IAS tone, and suggests miR-133a is feasible therapeutic target in aging-associated rectoanal incontinence.

2016-10-28 | GSE79350 | GEO

Rattus norvegicus

Project description:Role of differentially expressed microRNA-139-5p in the regulation of phenotypic internal anal sphincter smooth muscle tone

| PRJNA356547 | ENA

miR-139-5p induced gene expression alteration in glioma cells

Project description:To evaluate gene expression alteration following miR-139-5p transfection in glioma cells. We find a significant downregulation of two transcriptional factors, E2F3 and HoxA9. Total RNA were extracted from U87, LN229 and U251 glioma cells transfected with miR-139-5p or miRNA negative control.

2013-03-01 | E-GEOD-44728 | biostudies-arrayexpress

The miRNA miR-139-5p is a regulator of metastatic pathways in breast cancer.

Project description:Whole transcriptome Identification of direct targets of miR-139-5p using biotinylated pull-downs found that this miRNA has roles in breast cancer invasion and migration. MCF7 cells were transfected with biotinylated miR-139-5p. The miRNAs and target mRNA were pulled down with streptavidin and compared to the input control.

2013-12-01 | E-GEOD-40411 | biostudies-arrayexpress

Expression analysis of miR-139-5p mimic-treated EC109 cells

Project description:Investigation of whole genome gene expression level changes in miR-139-5p mimic-treated EC109 cells, compared to the scrambled negative controls. A four chip study using total RNA recovered from two separate cultures of miR-139-5p mimic-transfected EC109 cells and two separate cultures of scrambled negative control-transfected EC109 cells. Each chip measures the expression level of 44,049 genes from human esophageal cancer cell EC109 with three 60-mer probe pairs per gene.

2012-11-27 | E-GEOD-42486 | biostudies-arrayexpress

Hsa-miR-139-5p expression regulates the abundance of proteins related to poor survival cancer in CAL-62 thyroid cancer cell line

Project description:We studied the impact of hsa-miR-139-5p on the protein output by means of an iTRAQ-based approach. First, we established two CAL-62 isogenic cell lines expressing either the mature hsa-miR-139-5p or a non-targeting control upon a doxycycline inducible promoter (PTRE3G-tGFP, Dharmacon). Total proteins of P-tGFP-hsa-miR139-5p untreated or treated with doxycycline (1ug/ml) for 96 and 120 hours were isolated and labeled with iTRAQ® reagent 8-plex. Two independent experiments were performed.

2019-08-13 | PXD011901 | Pride

Expression analysis of miR-139-5p mimic-treated EC109 cells

Project description:Investigation of whole genome gene expression level changes in miR-139-5p mimic-treated EC109 cells, compared to the scrambled negative controls.

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mRNA profiling of MCF7 cells transfected with a miR-139-5p mimic

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Project description:To evaluate gene expression alteration following miR-139-5p transfection in glioma cells. We find a significant downregulation of two transcriptional factors, E2F3 and HoxA9.

2013-03-01 | GSE44728 | GEO

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Project description:Whole transcriptome Identification of direct targets of miR-139-5p using biotinylated pull-downs found that this miRNA has roles in breast cancer invasion and migration.

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