The miR-218/GAB2 axis regulates proliferation, invasion and EMT via the PI3K/AKT/GSK-3β pathway in prostate cancer

Tian, Jie; Mu, Lijun; Li, Xudong; Zhang, Xinwei; Xie, Enxu; Ma, Minghai; Wu, Dapeng; Du, Yifan

doi:10.1016/j.yexcr.2020.112128

Cited by 18 publications

(14 citation statements)

References 18 publications

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“…in the present study, GAB2 was identified as a direct target of miR-218-5p, which is consisted with a previous report (36). it is well reported that mir-218 inhibited the tumor angiogenesis in human cancer via regulating the GaB2/Pi3K/aKT signaling pathway in various cancer types (36,56). Thus, it was speculated that Sevo may have protective effects on Hiri via modulating the GaB2/aKT/mTor signaling pathway by increasing mir-218-5p expression.…”

Section: Discussionsupporting

confidence: 91%

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Role of microRNA‑218‑5p in sevoflurane‑induced protective effects in hepatic ischemia/reperfusion injury mice by regulating GAB2/PI3K/AKT pathway

Jiang

Zhang

et al. 2021

Mol Med Rep

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Section: Discussionsupporting

confidence: 91%

“…6B , agomiR-218-5p significantly increased the miR-218-5p levels, while antagomir-218-5p markedly decreased the miR-218-5p levels. Previous studies have reported that GAB2 is a target of miR-218-5p in prostate cancer (PCa) ( 36 ). To further validate these findings, a luciferase assay was performed.…”

Section: Resultsmentioning

confidence: 99%

Role of microRNA‑218‑5p in sevoflurane‑induced protective effects in hepatic ischemia/reperfusion injury mice by regulating GAB2/PI3K/AKT pathway

Jiang

Zhang

et al. 2021

Mol Med Rep

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“…Numerous studies have shown that activation of the PI3K/ Akt signaling pathway promotes EMT, proliferation, invasion, and migration in various types of cancer. [42][43][44][45] Furthermore, overexpression of SKA3 has been shown to activate the PI3K/Akt signaling pathway in cervical cancer and lung adenocarcinoma. 24,46 Recently, we discovered that SKA3 activates the PI3K/Akt pathway by binding to and stabilizing polo-like kinase 1 (PLK1).…”

Section: Discussionmentioning

confidence: 99%

miR-1207-5p suppresses laryngeal squamous cell carcinoma progression by downregulating SKA3 and inhibiting epithelial-mesenchymal transition

Wu¹,

Dai²,

Zhang³

et al. 2021

Molecular Therapy - Oncolytics

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Laryngeal squamous cell carcinoma (LSCC) is the second most common head and neck cancer. Previously, we discovered that miR-1207-5p was downregulated in LSCC. In this study, the clinical significance, function, and mechanism of miR-1207-5p in LSCC were investigated. Downregulation of miR-1207-5p was found to be strongly linked to the malignant progression of LSCC. Functional studies revealed that miR-1207-5p upregulation suppressed LSCC cell proliferation, invasion, migration, and xenograft tumor growth. Bioinformatics analysis revealed that miR-1207-5p target genes were involved in cell cycle regulation, proliferation, adhesion, and the phosphatidylinositol 3kinase (PI3K)/Akt pathway. Mechanistic studies revealed that miR-1207-5p interacts directly with the 3 0 untranslated region of spindle and kinetochore associated complex subunit 3 (SKA3) and downregulates SKA3 expression. Furthermore, SKA3 was found to be overexpressed in LSCC, and its high expression was associated with tumor progression and a poor prognosis. Rescue experiments demonstrated that miR-1207-5p inhibited the malignant phenotypes of LSCC via SKA3. Furthermore, miR-1207-5p upregulation or knockdown of SKA3 inhibited the epithelial-mesenchymal transition (EMT). Collectively, miR-1207-5p inhibited LSCC malignant progression by downregulating SKA3 and preventing EMT. These findings provide new insights into the mechanism of LSCC progression, as well as new potential biomarkers and therapeutic targets for LSCC diagnosis and treatment.

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“…Grb2 recruits and mediates the interaction with the adaptor protein Grb2-associated binder Gab2, and the SH2 domain could bind tyrosine-phosphorylated proteins, such as tyrosine-phosphorylated Gab2 [17,18]. Gab2 has been reported as an activator of phosphatidylinositol 3-kinase (PI3K) signaling pathway, since the interaction of SH2 domain of Grb2 with Gab2 recruited p85, which is the regulatory subunit of PI3K [19][20][21]. It has been demonstrated that PI3K activates its downstream effector Akt, which then promotes glycogen synthasekinase-3 (GSK3) phosphorylation [22].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of ZiBuPiYin Recipe on db/db Mice via PI3K-Akt Signaling Pathway by Activating Grb2

Ren

Weng

et al. 2021

Neural Plasticity

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Background. Diabetes-associated cognitive decline (DACD) is one of the nervous system dysfunctions induced by diabetes mellitus with cognitive impairment as the major symptom. In a previous preliminary proteomic study, we found that endoplasmic reticulum processing and PI3K-Akt signaling pathway might be impaired in DACD pathogenesis. In addition, growth factor receptor-bound protein 2 might be a crucial protein as a molecular target of the neuroprotective effects of ZiBuPiYin recipe (ZBPYR). Methods. In this study, 6-8 weeks aged db/db mice were treated with excipients or ZBPYR for 6 weeks. Body weight and RBG were recorded weekly. Oral glucose tolerance and insulin tolerance tests were used to assess insulin sensitivity. Morris water maze (MWM) tests were used to assess memory function. The expression of Grb2, Gab2, Akt, and GSK3β in mouse hippocampus and cerebral cortex were analyzed by Western blotting. Results. ZBPYR not only significantly reduced RGB and improved glucose tolerance and insulin resistance, but also improved spatial cognition in DACD mice. The expression of Grb2 and Gab2 in hippocampus and cerebral cortex of db/db mice was upregulated after treated with ZBPYR, and then affected the PI3K/Akt signaling pathway, and inhibited GSK3β overactivity. Conclusions. This study showed that ZBPYR could enhance the memory and learning ability of db/db mice. Such neuroprotective effect might be related to the activation of Grb2-PI3K/Akt signaling which might provide a novel therapeutic target for the clinical treatment of DACD.

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The miR-218/GAB2 axis regulates proliferation, invasion and EMT via the PI3K/AKT/GSK-3β pathway in prostate cancer

Cited by 18 publications

References 18 publications

Role of microRNA‑218‑5p in sevoflurane‑induced protective effects in hepatic ischemia/reperfusion injury mice by regulating GAB2/PI3K/AKT pathway

Role of microRNA‑218‑5p in sevoflurane‑induced protective effects in hepatic ischemia/reperfusion injury mice by regulating GAB2/PI3K/AKT pathway

miR-1207-5p suppresses laryngeal squamous cell carcinoma progression by downregulating SKA3 and inhibiting epithelial-mesenchymal transition

Neuroprotective Effects of ZiBuPiYin Recipe on db/db Mice via PI3K-Akt Signaling Pathway by Activating Grb2

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