MiR-21 regulates biological behavior through the PTEN/PI-3 K/Akt signaling pathway in human colorectal cancer cells

Xiong, Bin; Cheng, Yanan; Ma, Li; Cai-quan, Zhang

doi:10.3892/ijo.2012.1707

Cited by 178 publications

(125 citation statements)

References 65 publications

Supporting

Mentioning

113

Contrasting

Unclassified

Order By: Relevance

“…Moreover, Sheng et al [26] found that the protein kinase/phosphatase/phosphatidyl-inositol kinase (AKT/PTEN/ PI3K) signaling pathway is intimately linked with many malignant tumors and their progression, drug resistance, immunity, angiogenesis, and metastasis [27,28]. Furthermore, there have been several studies showing that miR-21 has a significant role in regulating the AKT/ PTEN/ PI3K signaling pathway and contributes to the initiation of carcinogenesis, tumor progression, and metastasis [29,30]. Sheng et al [26] reported that the PTEN gene is a direct target gene of miR-21.…”

Section: Discussionmentioning

confidence: 99%

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

et al. 2017

View full text Add to dashboard Cite

Objective: The objectives of this study were to evaluate the impact of two X-ray repair cross complementing 1 (XRCC1) gene polymorphisms (Arg194Trp and Arg399Gln) on the risk of development of colorectal cancer (CRC) and to assess the expression levels of microRNA-21 (miR-21) in CRC patients. Materials and Methods:A case-control cross sectional study was conducted on 50 CRC patients and 50 cancer-free subjects. DNA and miR-21 were extracted from whole blood samples. The expression levels of the XRCC1 polymorphisms and miR-21 were assessed by real-time PCR in all subjects of the study.Results: Genotype analysis revealed a significant association between CRC risk and both the Arg194Trp genotype (OR=11.407, 95% CI=4.039-32.221, p<0.001) and the Arg399Gln genotype (OR=3.778, 95% CI= 1.6-8.919, p=0.002). The expression levels of circulating miR-21 were able to detect CRC cases significantly (p=0.022) with a sensitivity of 82% and a specificity of 56% (Area under the curve (AUC)=0.633) but were unable to distinguish between early and late cases (AJCC classification) (p=0.194). Conclusion:The XRCC1 Arg194Trp and Arg399Gln polymorphisms both confer high susceptibility for the development of CRC. Circulating miR-21 expression levels are a potentially diagnostic non-invasive genetic marker of CRC.Keywords: Colorectal cancer, miRNA-21, XRCC1, DNA repair, single nucleotide polymorphisms ÖZ Amaç: Bu çalışmanın amacı iki XRCC1 gen polimorfizminin (Arg194Trp ve Arg399Gln) kolorektal kanser (KRK) gelişimi riski üzerindeki etkisini değerlendirmek ve KRK hastalarında microRNA-21 (miR-21) ekspresyonu düzeylerini incelemektir.Gereç ve Yöntemler: 50 KRK hastası ve 50 kansersiz denekle vaka-kontrollü bir kesitsel çalışma gerçekleşti-rildi. Tüm kan numunelerinden DNA ve miR-21 alındı. XRCC1 polimorfizmlerinin ve miR-21'in ekspresyon seviyeleri, çalışmadaki tüm deneklerde gerçek zamanlı PCR ile değerlendirildi. Bulgular: Genotip analizinde KRK riski ile Arg194Trp (OR=11.407, 95% CI=4.039-32.221, p<0,001) ve Arg399Gln (OR=3.778, 95% CI=1, p=0,002) genotipleri arasında önemli bir ilişki ortaya konuldu. Dolaşımdaki miR-21 ekspresyon düzeyleriyle KRK olguları %82 duyarlılık ve %56 özgüllük (AUC=0,633) ile anlamlı bir şekilde (p=0,022) saptanabildi, ancak erken ve geç vakalar ayırt edilemedi (AJCC sınıflandırması) (p=0,194).Sonuç: XRCC1 Arg194Trp ve Arg399Gln polimorfizmlerinin her ikisi de KRK gelişimine yüksek düzeyde yatkınlık göstermektedir. Dolaşımdaki miR-21 ekspresyon seviyeleri potansiyel olarak KRK'nın tanısal noninvasiv genetik belirtecidir.Anahtar Kelimeler: Kolorektal kanser, miRNA-21, XRCC1, DNA onarımı, SNPs Eurasian J Med 2017; 49: 132-6 Original Article

show abstract

Section: Discussionmentioning

confidence: 99%

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Although a large number of studies, including our study, indicate that in most solid tumors, miR-21 promotes the proliferation and metastasis of tumor cells by targeted inhibition of PTEN, a few investigators have reported conflicting results (Xiong et al 2013). Hatley et al (2010) reported that PTEN is not a target gene of miR-21 in NSCLC.…”

Section: Discussionmentioning

confidence: 98%

“…PTEN also has been confirmed as a target gene of miR-21 in nonsmall cell lung cancer (Zhang et al 2010), gastric cancer (Zhang et al 2012), cervical cancer (Xu et al 2015), and colorectal cancer (Xiong et al 2013). Deletions or inactivated mutations of PTEN can mediate the promotional effect of miR-21 on the proliferation, invasion and metastasis of tumor cells (Selcuklu et al 2009).…”

Section: Introductionmentioning

confidence: 99%

“…However, it remains to be investigated whether miR-21 could influence PTEN expression in WT. Based on various reports on miR-21 and PTEN expression in tumor tissues and cells (Selcuklu et al 2009;Zhang et al 2010;Zhang et al 2012;Xiong et al 2013;Xu et al 2015), we hypothesized that PTEN is a latent target gene of miR-21 in WT. Therefore, the purpose of this study was to analyze the correlation between the expressions of miR-21and PTEN and the clinicopathological parameters of WT, to elucidate the role of miR-21 in human SK-NEP-1 WT cell line and to further explore the targeting regulatory relationship between miR-21 and PTEN in WT.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Over-Expression of miR-21 and Lower PTEN Levels in Wilms’ Tumor with Aggressive Behavior

Cui

Liu

Zhang

et al. 2017

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Wilms' tumor (WT) is the most common pediatric kidney tumor. MiR-21 is one of the most frequently overexpressed microRNAs in solid tumors, while phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is the most highly mutated tumor suppressor gene. The aim of this study was to investigate the relationship between miR-21 and PTEN in WT. The expression levels of miR-21 and the PTEN protein were determined by qRT-PCR and Western blot analyses in WT specimens, respectively. In WT tissues, the miR-21 expression levels were significantly higher and the PTEN protein levels were significantly lower, compared to the adjacent non-tumorous renal tissues. The higher levels of miR-21 and lower levels of PTEN were correlated with age (> 24 months), late clinical stage, unfavorable histopathological type and lymphatic metastasis. A univariate linear regression analysis indicated a significant correlation between higher miR-21 levels and lower PTEN levels. Using the SK-NEP-1 WT cell line, we showed that the decreased expression levels of miR-21 promoted cell proliferation and invasion, but inhibited apoptosis. Importantly, lowered expression levels of miR-21 increased the expression levels of PTEN protein and decreased the expression levels of phosphoinositide 3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT), each of which functions in the downstream signaling pathway. Dual luciferase-reporter assays indicated that PTEN mRNA was a direct target of miR-21. In conclusion, higher miR-21 levels and lower PTEN protein levels are predictive biomarkers for poor prognosis of WT patients. Over-expression of miR-21 promotes aggressive behavior of WT by targeting PTEN.

show abstract

“…Moreover, we observed that pretreatment with paeonol also reversed the suppression of PTEN expression induced by ox-LDL. Interestingly, studies have demonstrated that PTEN is a downstream target gene of miR-21 in cancers [16][17][18][19] , because its 3'-UTR contains 16 base sites that are complementary to the miR-21 sequence [1,20] . However, it is unknown whether paeonol-mediated protection of VECS against ox-LDL injury involves miR-21-dependent modulation of PTEN.…”

Section: Discussionmentioning

confidence: 99%

Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release

Liu¹,

Chen²,

Dai

2014

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Paeonol (2′-hydroxy-4′-methoxyacetophenone) from Cortex moutan root is a potential therapeutic agent for atherosclerosis. This study sought to investigate the mechanisms underlying anti-inflammatory effects of paeonol in rat vascular endothelial cells (VECs) in vitro. Methods: VECs were isolated from rat thoracic aortas. The cells were pretreated with paeonol for 24 h, and then stimulated with ox-LDL for another 24 h. The expression of microRNA-21 (miR-21) and PTEN in VECs was analyzed using qRT-PCR. The expression of PTEN protein was detected by Western blotting. TNF-α release by VECs was measured by ELISA. Results: Ox-LDL treatment inhibited VEC growth in dose-and time-dependent manners (the value of IC 50 was about 20 mg/L at 24 h). Furthermore, ox-LDL (20 mg/L) significantly increased miR-21 expression and inhibited the expression of PTEN, one of downstream target genes of miR-21 in VECs. In addition, ox-LDL (20 mg/L) significantly increased the release of TNF-α from VECs. Pretreatment with paeonol increased the survival rate of ox-LDL-treated VECs in dose-and time-dependent manners. Moreover, paeonol (120 μmol/ L) prevented ox-LDL-induced increases in miR-21 expression and TNF-α release, and ox-LDL-induced inhibition in PTEN expression. A dual-luciferase reporter assay showed that miR-21 bound directly to PTEN's 3'-UTR, thus inhibiting PTEN expression. In ox-LDL treated VECs, transfection with a miR-21 mimic significantly increased miR-21 expression and inhibited PTEN expression, and attenuated the protective effects of paeonol pretreatment, whereas transfection with an miR-21 inhibitor significantly decreased miR-21 expression and increased PTEN expression, thus enhanced the protective effects of paeonol pretreatment. Conclusion: miR-21 is an important target of paeonol for its protective effects against ox-LDL-induced VEC injury, which may play critical roles in development of atherosclerosis.

show abstract

MiR-21 regulates biological behavior through the PTEN/PI-3 K/Akt signaling pathway in human colorectal cancer cells

Cited by 178 publications

References 65 publications

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

Over-Expression of miR-21 and Lower PTEN Levels in Wilms’ Tumor with Aggressive Behavior

Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release

Contact Info

Product

Resources

About