miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3

Boufraqech, Myriem; Zhang, Lisa; Jain, Meenu; Patel, Dhaval; Ellis, Ryan J.; Xiong, Yin; He, Mei; Nilubol, Naris; Merino, María J.; Kebebew, Electron

doi:10.1530/erc-14-0077

Cited by 95 publications

(82 citation statements)

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“…In this study, we detected the expression of AKT3 in CRC and found that it was significantly upregulated. Notably, AKT3 has been found to be regulated by several miRNAs, such as miR-29a, miR-338-3p and miR-145 [32–34]. To further verify whether AKT3 was a target gene of miR-384 in CRC, luciferase reporter assay, qRT-PCR, and western blot were conducted.…”

Section: Discussionmentioning

confidence: 99%

MiR-384 inhibits the proliferation of colorectal cancer by targeting AKT3

et al. 2018

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BackgroundGrowing evidence suggests that MiRNAs play essential roles in the initiation and progression of colorectal cancer (CRC). The aberrant expression of miR-384 has been reported in some cancers. However, the role and mechanism of miR-384 in CRC proliferation remains unknown.MethodsThe expression of miR-384 was detected in CRC and their paired normal tissues by real-time PCR. In vivo and in vitro assays were conducted to confirm the role of miR-384 in the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro assays were used to confirm that AKT3 was the target gene of miR-384. Finally, Spearman’s correlation analyses was carried out to analyze the relationship between miR-384 expression and AKT3 expression in CRC.ResultsMiR-384 was down‑regulated in CRC tissues. The in vivo and vitro functional assays verified that the ectopic upregulation of miR-384 inhibited the proliferation of CRC and the inhibition of miR-384 promoted the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro functional assays confirmed AKT3 as the target gene of miR-384. The expression of miR-384 was negatively correlated with the expressions of AKT3.ConclusionOur study verified that miR-384 could significantly suppress the proliferation of CRC by directing targeting AKT3.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0628-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

MiR-384 inhibits the proliferation of colorectal cancer by targeting AKT3

et al. 2018

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“…Evidence indicates that the PI3K/Akt pathway regulates the epithelial-mesenchymal transition, cell cycle, angiogenesis and apoptosis, and has an important role in tumor progression (26)(27)(28). The PI3K/Akt pathway was reported to be activated in PTC and to be involved in cell proliferation and migration (29).…”

Section: Discussionmentioning

confidence: 99%

Ang1/Tie2 induces cell proliferation and migration in human papillary thyroid carcinoma via the PI3K/AKT pathway

Yao

et al. 2017

Oncol Lett

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Abstract. The angiopoietin 1 (Ang1)/angiopoietin receptor (Tie2) signaling pathway may have a notable role in the pathogenesis of inflammatory diseases. The abnormal expression of angiopoietin 1 and Tie2 has also been reported in various malignant tumors, including papillary thyroid carcinoma (PTC). However, the role and mechanism of the Ang1/Tie2 pathway in the progression of PTC remains unclear. Therefore, the aims of the present study were to clarify this. Significantly high expression levels of Ang1 and Tie2 were observed in PTC tissues and cell lines. Furthermore, MTT and wound-healing assays revealed that the Ang1-mediated stimulation of human PTC cells resulted in increased proliferation and migration. Conversely, the downregulation of Tie2 levels using short hairpin RNA targeted at Tie2 abrogated the Ang1-mediated effect on cell proliferation and migration. In studying the expression of phosphoinositide-3 kinase (PI3K)/RAC serine/threonine-protein kinase (Akt) pathway, the upregulation of Ang1/Tie2 was found to be associated with the activation of the PI3K/Akt pathway in PTC. In conclusion, the data from the present study indicated that the Ang1/Tie2 induces PTC oncogenesis via the PI3K/Akt pathway, providing novel insights into human PTC therapy. IntroductionPapillary thyroid carcinoma (PTC) is the most prevalent histological thyroid carcinoma subtype, accounting for ~80% of cases (1,2). Although recent advances in diagnosis and treatment strategies have been made in clinical and experimental oncology, ≤30% of patients present with local/regional recurrence or distant metastasis within 10 years (2,3). Thus, the elucidation of the molecular mechanisms underlying PTC progression is urgently required in order to develop effective diagnostic, prognostic and therapeutic strategies.Receptor tyrosine kinases are cell surface proteins that transduce signals from extracellular growth factors intracellularly, to elicit biological responses (4). Receptor tyrosine kinases act as potent oncoproteins and are abnormally expressed in a number of cancer types, including gliomas (5). Angiopoietin-1 (Ang1) receptor (TEK, also known as Tie2) is a receptor tyrosine kinase that was identified as an endothelial-cell-specific receptor with a critical role in the modulation of vasculogenesis and remodeling (6). Tie2 expression occurs, and is partially maintained, during differentiation in human neural stem cells (7), but not in mature neurons (8). Dysregulated Tie2 expression has also been observed in several tumor tissues, including oral squamous cell carcinoma, breast, gastric, leukemia and thyroid cancer (9-13). These studies revealed that Tie2 expression is associated with the identification and prognosis of these cancer types (12). Ang1 is a secreted ligand for Tie2 that maintains vascular plasticity, perturbations in which can contribute to abnormal vascular growth (4). Daly et al (6) revealed that Ang2 functions as a Tie2 agonist in tumor models, limiting the effects of VEGF inhibition (6). Mitsutake et al (13) revealed ...

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“…However, Kent et al (23) observed that RREB1 can inhibit the expression of miR-145. In addition, studies have demonstrated that miR-145 can inhibit the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway through regulating the expression of integrin-linked kinase (24,25).…”

Section: Discussionmentioning

confidence: 99%

Role of miR-145 in chronic constriction injury in rats

Pang

Tang

Zhang

2016

Experimental and Therapeutic Medicine

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Abstract. The present study aims to investigate the effects and underlying mechanisms of miRNA-145 (miR-145) in rat models of chronic constriction injury (CCI). Rats were randomly divided into control, sham, CCI, agomiRNA (agomiR)-normal control (NC) and agomiR-145 groups (n=25 in each group); in addition, 30 rats with CCI were divided into small hairpin (sh)RNA-NC and shRNA-ras responsive element binding protein 1 (RREB1) groups. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) were detected. Reverse transcription-quantitative polymerase chain reaction was used to detect miR-145 expression levels, and western blotting was performed to measure RREB1 and phosphorylated-protein kinase B (p-AKT) expression levels. In addition, a dual luciferase reporter assay was conducted to identify the target gene of miR-145. PWMT and PWTL were decreased in CCI rats and this decrease was alleviated by miR-145 injection. At 1, 3, 5 and 7 days after CCI, miR-145 expression level in the spinal cord tissue of rats in the CCI group was significantly decreased compared with 1 day before CCI (P<0.05). Compared with the CCI group, miR-145 expression level in the agomiR-145 group was significantly higher (P<0.05). In addition, expression levels of RREB1 and p-AKT were significantly increased in the CCI group and significantly decreased in the agomiR-145 group (P<0.05). Furthermore, knockdown of RREB1 expression by shRNA-RREB1 significantly increased values of PWMT and PWTL, decreased expression levels of RREB1 and p-AKT, and increased miR-145 expression levels (P<0.05). Further investigation demonstrated that miR-145 can bind with RREB1 mRNA. In conclusion, miR-145 may be involved in the development of CCI through regulating the expression of RREB1.

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miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3

Cited by 95 publications

References 48 publications

MiR-384 inhibits the proliferation of colorectal cancer by targeting AKT3

MiR-384 inhibits the proliferation of colorectal cancer by targeting AKT3

Ang1/Tie2 induces cell proliferation and migration in human papillary thyroid carcinoma via the PI3K/AKT pathway

Role of miR-145 in chronic constriction injury in rats

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