miR-218 inhibits the invasion and migration of colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway

Zhang, Xiangliang; Shi, Huijuan; Tang, Hua; Fang, Zhiyuan; Wang, Jiping; Cui, Shuzhong

doi:10.3892/ijmm.2015.2126

Cited by 68 publications

(50 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Integrin β-1 receptors are associated with increased invasiveness in many cancers (37–39) and induce cell proliferation and survival (40). PI3K/Akt signaling, the most frequently altered pathway in many cancers (41,42), was inhibited by miR-6126 and was associated with integrin β-1 protein inhibition. Activation of PI3K/Akt signals has been known to play major roles in migration (43), invasion (44), angiogenesis (45), and proliferation (46).…”

Section: Discussionmentioning

confidence: 99%

Ubiquitous Release of Exosomal Tumor Suppressor miR-6126 from Ovarian Cancer Cells

et al. 2016

View full text Add to dashboard Cite

Cancer cells actively promote their tumorigenic behavior by reprogramming gene expression. Loading intraluminal vesicles with specific miRNAs and releasing them into the tumor microenvironment as exosomes is one mechanism of reprogramming whose regulation remains to be elucidated. Here, we report that miR-6126 is ubiquitously released in high abundance from both chemosensitive and chemoresistant ovarian cancer cells via exosomes. Overexpression of miR-6126 was confirmed in healthy ovarian tissue compared to ovarian cancer patient samples and correlated with better overall survival in high-grade serous ovarian cancer patients. miR-6126 acted as a tumor suppressor by directly targeting integrin β1, a key regulator of cancer cell metastasis. miR-6126 mimic treatment of cancer cells resulted in increased miR-6126 and decreased integrin β1 mRNA levels in the exosome. Functional analysis showed that treatment of endothelial cells with miR-6126 mimic significantly reduced tube formation as well as invasion and migration capacities of ovarian cancer cells in vitro. Administration of miR-6126 mimic in an orthotopic mouse model of ovarian cancer elicited a relative reduction in tumor growth, proliferating cells and microvessel density. miR-6126 inhibition promoted oncogenic behavior by leading ovarian cancer cells to release more exosomes. Our findings provide new insights into the role of exosomal miRNA-mediated tumor progression and suggest a new therapeutic approach to disrupt oncogenic phenotypes in tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

Ubiquitous Release of Exosomal Tumor Suppressor miR-6126 from Ovarian Cancer Cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Furthermore, SEMA3F prevented metastasis of colorectal cancer by PI3K/Akt-dependent downregulation of the ASCL2/CXCR4 Axis [49]. Ginsenoside Rh2 inhibited metastasis of glioblastoma multiforme through Akt-regulated MMP13 [50]. MiR-218 inhibited the invasion and migration of colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway [51].…”

Section: Figmentioning

confidence: 99%

Potential role of O‐GlcNAcylation and involvement of PI3K/Akt1 pathway in the expression of oncogenic phenotypes of gastric cancer cells in vitro

Zhang

Chen

2015

Biotech and App Biochem

View full text Add to dashboard Cite

O-GlcNAcylation is a monosaccharide modification by a residue of N-acetylglucosamine (GlcNAc) attached to serine or threonine moieties on nuclear and cytoplasmic proteins. O-GlcNAcylation is dynamically regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Increasing evidence suggests that O-GlcNAcylation is involved in a variety of human cancers. However, the exact role of O-GlcNAcylation in tumor progression remains unclear. Here, we show that O-GlcNAcylation accelerates oncogenic phenotypes of gastric cancer. First, cell models with increased or decreased O-GlcNAcylation were constructed by OGT overexpression, downregulation of OGA activity with specific inhibitor Thiamet-G, or silence of OGT. MTT assays indicated that O-GlcNAcylation increased proliferation of gastric cancer cells. Soft agar assay and Transwell assays showed that O-GlcNAcylation significantly enhanced cellular colony formation, migration, and invasion in vitro. Akt1 activity was stimulated by upregulation of phosphorylation at Ser473 mediated by elevated O-GlcNAcylation. The enhanced cell invasion by Thiamet-G treatment was suppressed by PI3K inhibitor LY294002. Although the cell invasion induced by Thiamet-G was reduced by Akt1 shRNA, it was still higher in comparison with that to the control (cells with Akt1 shRNA alone). And Akt1 overexpression promoted Thiamet-G-induced cell invasion. These results suggested that O-GlcNAcylation enhanced oncogenic phenotypes possibly partially involving PI3K/Akt signaling pathway.

show abstract

“…The association between miRNAs and tumour chemo-sensitivity has recently attracted increased attention [8]. Some research has shown that miR-218 acts as a tumour-suppressing miRNA in many cancers, including glioma, cervical cancer and colon cancer [11-13]. Our previous study showed that miR-218 expression was down-regulated in clinical bladder cancer tissues and inhibited the proliferation, migration and invasion of bladder cancer cells [14].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

Yang

Cheng

Zhang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. Methods: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2’, 7’-dichlorodihydro-fluorescein diacetate, respectively. Results: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. Conclusions: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.

show abstract

miR-218 inhibits the invasion and migration of colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway

Cited by 68 publications

References 52 publications

Ubiquitous Release of Exosomal Tumor Suppressor miR-6126 from Ovarian Cancer Cells

Ubiquitous Release of Exosomal Tumor Suppressor miR-6126 from Ovarian Cancer Cells

Potential role of O‐GlcNAcylation and involvement of PI3K/Akt1 pathway in the expression of oncogenic phenotypes of gastric cancer cells in vitro

MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

Contact Info

Product

Resources

About