miRNA‑29a inhibits colon cancer growth by regulation of the PTEN/Akt/GSK3β and Wnt/β‑catenin signaling pathways

Han, Xiaofeng; Zheng, Jianwei; Wang, Yunlei; Gao, Zhigang

doi:10.3892/ol.2018.8905

Cited by 15 publications

(17 citation statements)

References 35 publications

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“…β-catenin is not degraded and accumulates in the cytoplasm. Inhibition of the Wnt/β-catenin signaling pathway in colon cancer has been found to alleviate the degree of deterioration of colon cancer (47–49). In the present study, with the activation of the Wnt/β-catenin signal pathway, the Wnt activator SB2617763 was found to reverse the inhibitory effect of siSTC2 on Wnt/β-catenin and cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Effect of STC2 gene silencing on colorectal cancer cells

Zhou

Fang

et al. 2019

Mol Med Report

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Stanniocalcin 2 (STC2), a secretory glycoprotein hormone, regulates many biological processes including cell proliferation, apoptosis, tumorigenesis and atherosclerosis. However, the effect of STC2 on proliferation, migration and epithelial-mesenchymal transition (EMT) progression in human colorectal cancer (CRC) cells remains poorly understood. The expression level of STC2 was determined by quantitative real-time polymerase chain reaction (qPCR) and western blot analysis. Cell Counting Kit-8 (CCK-8) was used to detect the viability of SW480 cells. The invasion and migration of cells were identified by wound healing and Transwell assays. The mRNA and protein expression levels of β-catenin, matrix metalloproteinase (MMP)-2, MMP-9, E-cadherin and vimentin were assessed by qPCR and western blot analysis. In the present study, it was demonstrated that STC2 was highly expressed in the CRC cell lines. After silencing of STC2 , the cell viability, migration and invasion were significantly reduced. Silencing of STC2 in the CRC Sw480 cells increased the expression of E-cadherin and decreased the expression of vimentin, MMP-2 and MMP-9, compared to those in the normal and empty vector group. Furthermore, the expression of β-catenin in the STC2 gene silenced group was suppressed, and the expression of β-catenin was reversed by Wnt activator, SB216763. These results demonstrated that STC2 participates in the development and progression of CRC by promoting CRC cell proliferation, survival and migration and activating the Wnt/β-catenin signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Effect of STC2 gene silencing on colorectal cancer cells

Zhou

Fang

et al. 2019

Mol Med Report

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“…However, the biological functions of miR-29a might be controversial. It has been shown that miR-29a downregulates the activity of Wnt/β-catenin signaling in colon cancer 32. In addition, the cytokines, including FZD3, FZD5, DVL3, FRAT2, and CK2A2, involved in Wnt/β-catenin signaling have been showed to be the potential targets of miR-29 in miR-29 gain- and loss-of-function microarray experiments in primary human articular chondrocytes 5.…”

Section: Discussionmentioning

confidence: 99%

<p>TMF inhibits miR-29a/Wnt/β-catenin signaling through upregulating Foxo3a activity in osteoarthritis chondrocytes</p>

Huang¹,

Chen²,

Shi³

et al. 2019

DDDT

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Background: miR-29a, a downstream factor of Wnt/β-catenin signaling, promotes the activity of the Wnt/β-catenin signaling in a positive feedback loop. Our previous work showed that 5,7,3ʹ,4ʹ-tetramethoxyflavone (TMF), a major constituent from Murraya exotica L., exhibited chondroprotective activity by inhibiting the activity of Wnt/β-catenin signaling. Purpose: To investigate whether TMF showed the inhibitory effects on miR-29a/β-catenin signaling by up regulation of Foxo3a expression. Methods: Rat knee OA models were duplicated by using Hulth’s method. TMF (5 μg/mL and 20 μg/mL) was used for administration to cultured cells, which were isolated from the rat cartilages. Analysis of chondrocytes apoptosis, gene expression, and protein expression were conducted. In addition, miR-29a mimics and pcDNA3.1(+)-Foxo3a vector were used for transfection, luciferase reporter assay for detecting the activity of Wnt/β-catenin signaling, and co-immunoprecipitation for determining proteins interaction. Results: TMF down regulated miR-29a/β-catenin signaling activity and cleaved caspase-3 expression and up regulated Foxo3a expression in OA rat cartilages. In vitro, miR-29a mimics down regulated the expression of Foxo3a and up regulated the activity of Wnt/β-catenin signaling and cleaved caspase-3 expression. TMF ameliorated miR-29a/β-catenin-induced chondrocytes apoptosis by up regulation of Foxo3a expression. Conclusion: TMF exhibited chondroprotective activity by up regulating Foxo3a expression and subsequently inhibiting miR-29a/Wnt/β-catenin signaling activity.

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“…MicroRNA-29a has previously been reported to promote hepatoma cell migration by directly targeting PTEN, a key regulator of migration in many cell types [17, 50]. We observed that miR-29a robustly downregulates PTEN in glioblastoma cells that have intact PTEN function.…”

Section: Discussionmentioning

confidence: 52%

MicroRNA-29a activates a multi-component growth and invasion program in glioblastoma

Zhao

Huang

Kim

et al. 2019

J Exp Clin Cancer Res

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BackgroundGlioblastoma is a malignant brain tumor characterized by rapid growth, diffuse invasion and therapeutic resistance. We recently used microRNA expression profiles to subclassify glioblastoma into five genetically and clinically distinct subclasses, and showed that microRNAs both define and contribute to the phenotypes of these subclasses. Here we show that miR-29a activates a multi-faceted growth and invasion program that promotes glioblastoma aggressiveness.MethodsmicroRNA expression profiles from 197 glioblastomas were analyzed to identify the candidate miRNAs that are correlated to glioblastoma aggressiveness. The candidate miRNA, miR-29a, was further studied in vitro and in vivo.ResultsMembers of the miR-29 subfamily display increased expression in the two glioblastoma subclasses with the worst prognoses (astrocytic and neural). We observed that miR-29a is among the microRNAs that are most positively-correlated with PTEN copy number in glioblastoma, and that miR-29a promotes glioblastoma growth and invasion in part by targeting PTEN. In PTEN-deficient glioblastoma cells, however, miR-29a nevertheless activates AKT by downregulating the metastasis suppressor, EphB3. In addition, miR-29a robustly promotes invasion in PTEN-deficient glioblastoma cells by repressing translation of the Sox4 transcription factor, and this upregulates the invasion-promoting protein, HIC5. Indeed, we identified Sox4 as the most anti-correlated predicted target of miR-29a in glioblastoma. Importantly, inhibition of endogenous miR-29a decreases glioblastoma growth and invasion in vitro and in vivo, and increased miR-29a expression in glioblastoma specimens correlates with decreased patient survival.ConclusionsTaken together, these data identify miR-29a as a master regulator of glioblastoma growth and invasion.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1026-1) contains supplementary material, which is available to authorized users.

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miRNA‑29a inhibits colon cancer growth by regulation of the PTEN/Akt/GSK3β and Wnt/β‑catenin signaling pathways

Cited by 15 publications

References 35 publications

Effect of STC2 gene silencing on colorectal cancer cells

Effect of STC2 gene silencing on colorectal cancer cells

<p>TMF inhibits miR-29a/Wnt/β-catenin signaling through upregulating Foxo3a activity in osteoarthritis chondrocytes</p>

MicroRNA-29a activates a multi-component growth and invasion program in glioblastoma

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