Dataset Information

MicroRNA-142-3p Promotes Cellular Invasion of Colorectal Cancer Cells by Activation of RAC1.

ABSTRACT:

Background

Colorectal cancer has been proved more difficult to treat owing to potently malignant metastasis. The present study was aimed to explore the functional role of miR-142-3p in cell migration and invasion of colorectal cancer cells, as well as its underlying mechanism.

Materials and methods

Expressions of miR-142-3p were analyzed in colorectal cancer tissues and cell lines. Ras-related C3 botulinum toxin substrate 1 (RAC1) was predicted as a target of miR-142-3p using software and network resources. SW480 cells were transfected with miR-142-3p expression plasmid and miR-142-3p silencer plasmid, and the expression of RAC1 and the cellular invasion were measured.

Results

In colorectal cancer cells transfected with miR-142-3p expression plasmid, RAC1 was specifically upregulated and invasiveness of cells was downregulated. Moreover, RAC1 was significantly associated with tumor stage ( P = .029) and tumor metastasis ( P = .012).

Conclusion

miR-142-3p promotes cellular invasion in colorectal cancer cells by activating RAC1. Thereby, miR-142-3p is a potential candidate for molecular targeted therapy of colorectal cancer.

SUBMITTER: Gao X

PROVIDER: S-EPMC6069031 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

MicroRNA-142-3p Promotes Cellular Invasion of Colorectal Cancer Cells by Activation of RAC1.

Gao Xiang X Xu Wenhuan W Lu Tingxun T Zhou Jialiang J Ge Xiaosong X Hua Dong D

Technology in cancer research & treatment 20180101

<h4>Background</h4>Colorectal cancer has been proved more difficult to treat owing to potently malignant metastasis. The present study was aimed to explore the functional role of miR-142-3p in cell migration and invasion of colorectal cancer cells, as well as its underlying mechanism.<h4>Materials and methods</h4>Expressions of miR-142-3p were analyzed in colorectal cancer tissues and cell lines. Ras-related C3 botulinum toxin substrate 1 (RAC1) was predicted as a target of miR-142-3p using soft ...[more]

PMID: 30064309

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Project description:Aberrant expression of microRNAs (miRNAs/miRs) is associated with the initiation and progression of colorectal cancer (CRC), but how they regulate colorectal tumorigenesis is still unknown. The present study was designed to investigate the expression profile of miRNAs in human CRC tissues, and to reveal the molecular mechanism of miRNA‑142‑3p in suppressing colon cancer cell proliferation. The expression of miRNA was examined using an Exiqon miRNA array. Bioinformatics was used to predict the target genes of differentially expressed miRNAs and to analyze their biological function in CRC. The effect of miR‑142‑3p in colon cancer cells was evaluated in vitro using cell proliferation, colony formation and Transwell assays. Dual‑luciferase reporter gene assays were performed to investigate the association between miR‑142‑3p and Rac family small GTPase 1 (RAC1). The effect of miR‑142‑3p regulation on colon cancer proliferation was assessed through western blotting and quantitative polymerase chain reaction analysis. Compared with their expression in adjacent non‑cancer mucosal tissues, 76 miRNAs were upregulated and 102 miRNAs were downregulated in CRC. One of the most significantly and differentially regulated miRNAs was miR‑142‑3p, which was downregulated in 81.0% (51/63) of primary CRC tissues. After transfection of miR‑142‑3p mimics into colon cancer cells, proliferation and colony formation were decreased, and migration and invasion were markedly suppressed. RAC1 was a possible target of miR‑142‑3p, which was confirmed by dual‑luciferase reporter assay. Transfection of miR‑142‑3p mimics decreased the levels of RAC1 and suppressed epithelial‑to‑mesenchymal transition in colon cancer cells. The phosphorylation of extraceullar signal‑regulated kinase (ERK) was decreased significantly by the inhibition of RAC1 or transfection of miR‑142‑3p mimics in colon cancer cells. In conclusion, aberrant miRNAs are implicated in CRC. Decreased expression of miR‑142‑3p may be associated with CRC tumorigenesis via Rac1‑ERK signaling.

Project description:Purpose: Uveal melanoma (UM) is the most frequent metastatic ocular tumor in adults. Therapeutic intervention remains ineffective since none of the novel procedures used to treat this disease increased survival rates. To deal with this limitation, additional studies are required to clarify its pathogenesis. The current study focused on describing how epigenetic modulation by miR-142-3p affects changes in some cellular functions underlying UM pathogenesis. Methods and results: Microarray analysis identified 374 miRNAs which were differentially expressed between UM cells and uveal melanocytes. miR-142-3p was one of the 10 most downregulated miRNAs. Quantitative RT-PCR analysis confirmed that miR-142-3p expression levels were significantly decreased in both UM cell lines and clinical specimens. The results of the MTS, clone formation, scratch wound, transwell assays, and in vivo biofluorescence imaging showed that miR-142-3p overexpression significantly inhibited cell proliferation, migration, and invasiveness. Nevertheless, miR-142-3p did not affect cell apoptotic activity or sensitivity to doxorubicin. Cell cycle and EdU analysis showed that miR-142-3p overexpression induced G1/G2 cell cycle arrest and reduced DNA synthesis in UM cells. Microarray analysis showed that miR-142-3p mainly regulates the TGFβ signaling pathway, and those in which MAPK and PI3K-Akt are constituents. Functional interactions between miR-142-3p and CDC25C, TGFβR1, GNAQ, WASL, and RAC1 target genes were confirmed based on the results of the luciferase reporter assay and Western blot analysis. CDC25C or RAC1 downregulation is in agreement with cell cycle arrest and DNA synthesis disorder induction, while downregulation of TGFβR1, GNAQ, WASL, or RAC1 accounts for declines in cell migration. Conclusion: miR-143-3p is a potential therapeutic target to treat UM since overriding its declines in expression that occur in this disease reversed the pathogenesis of this disease. Such insight reveals novel biomarker for decreasing UM vitality and for improved tracking of tumor progression.

Project description:The D1 dopamine receptor subtype is expressed in the brain, kidney and lymphocytes. D1 receptor function has been extensively studied and the receptor has been shown to modulate a wide range of physiological functions and behaviors. The expression of D1 receptor is known to change during development, disease states and chronic treatment; however, the molecular mechanisms that mediate the changes in D1 receptor expression under these circumstances are not well understood. While previous studies have identified extracellular factors and signaling mechanisms regulating the transcription of D1 receptor gene, very little is known about other regulatory mechanisms that modulate the expression of the D1 receptor gene. Here we report that the D1 receptor is post-transcriptionally regulated during postnatal mouse brain development and in the mouse CAD catecholaminergic neuronal cell line. We demonstrate that this post-transcriptional regulation is mediated by a molecular mechanism involving noncoding RNA. We show that the 1277 bp 3'untranslated region of D1 receptor mRNA is necessary and sufficient for mediating the post-transcriptional regulation. Using deletion and site-directed mutagenesis approaches, we show that the D1 receptor post-transcriptional regulation is specifically mediated by microRNA miR-142-3p interacting with a single consensus binding site in the 1277 bp 3'untranslated region of D1 receptor mRNA. Inhibiting endogenous miR-142-3p in CAD cells increased endogenous D1 receptor protein expression levels. The increase in D1 receptor protein levels was biologically significant as it resulted in enhanced D1 receptor-mediated signaling, determined by measuring the activation of both, adenylate cyclase and, the dopamine- and cAMP-regulated phosphoprotein, DARPP-32. We also show that there is an inverse correlation between miR-142-3p levels and D1 receptor protein expression in the mouse brain during postnatal development. This is the first study to demonstrate that the post-transcriptional regulation of D1 receptor expression is mediated by microRNA-induced translational suppression.

Dataset Information

MicroRNA-142-3p Promotes Cellular Invasion of Colorectal Cancer Cells by Activation of RAC1.

Background

Materials and methods

Results

Conclusion

Publications

MicroRNA-142-3p Promotes Cellular Invasion of Colorectal Cancer Cells by Activation of RAC1.

Similar Datasets

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