<scp>MicroRNA</scp>‐221 targeting <scp>PI3‐K/Akt</scp> signaling axis induces cell proliferation and <scp>BCNU</scp> resistance in human glioblastoma

Xie, Qiang; Yan, Yi; Huang, Zuoping; Zhong, Xueyun; Huang, Lei

doi:10.1111/neup.12129

Cited by 41 publications

(24 citation statements)

References 28 publications

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“…Akt is a key molecule in the PI3K signaling pathway, and the activity of Akt is tightly regulated by its phosphorylation status (33). pAkt is activated in various types of OSCC and has been confirmed to promote cell proliferation, invasion, migration and reduce apoptosis (23,35). Research has shown that loss of PTEN function may be a factor leading to Akt signaling pathway activation and is consistent with the results of the present study (14,36).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-221/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN

et al. 2016

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MicroRNA-221 and microRNA-222 (miR-221/222) have been identified as oncogenes and confirmed to be overexpressed in various types of cancer. However, the regulation mechanism of miR-221/222 in oral squamous cell carcinoma (OSCC) remains to be fully elucidated. Previously, an miR-221/222 sponge was successfully constructed and its effect on the downregulation of miR-221/222 expression was investigated. In the present study, the dual luciferase reporter assay revealed a phosphatase and tensin homolog (PTEN) deletion on chromosome 10 to be a target gene of miR-221/222. It was also demonstrated that miR-221/222 suppression by transfection with an miR-221/222 sponge in vitro resulted in upregulation of PTEN. Notably, the proliferation and invasiveness of the miR-221/222 sponge-transfected cells was significantly inhibited, while apoptosis was promoted, when determined by Cell Counting Kit-8, Transwell assays and flow cytometry. The results of the present study prove that miR-221/222 may downregulate the expression of PTEN in OSCC cells and function as oncogenes, providing a novel insight into the underlying mechanism of OSCC tumorigenesis. The present study suggests that upregulating the expression of PTEN by downregulation of miR-221/222 may be a potential treatment for OSCC.

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Section: Discussionmentioning

confidence: 99%

Downregulation of miR-221/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN

et al. 2016

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“…Whether at the mRNA or protein level, export of such molecules may offer a duel immune evasion strategy in which tumors can increase proliferation while inhibiting immune effector cell cytolytic activity. Finally, recent evidence indicates that circulating specific exogenous miRs, which are also packaged in exosomes, can modify NK cell function (52), and several miRs including miR-21, miR-26a, miR-214, miR-221, and miR-222 have each been shown to negatively regulate PTEN (36,(53)(54)(55)(56). This creates several potential therapeutic targets for enhancing NK cell function that warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

PTEN Is a Negative Regulator of NK Cell Cytolytic Function

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Chen

et al. 2015

The Journal of Immunology

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Human NK cells are characterized by their ability to initiate an immediate and direct cytolytic response to virally infected or malignantly transformed cells. Within human peripheral blood, the more mature CD56dim NK cell efficiently kills malignant targets at rest, whereas the less mature CD56bright NK cells cannot. In this study, we show that resting CD56bright NK cells express significantly more phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein when compared with CD56dim NK cells. Consistent with this, forced overexpression of PTEN in NK cells resulted in decreased cytolytic activity, and loss of PTEN in CD56bright NK cells resulted in elevated cytolytic activity. Comparable studies in mice showed PTEN overexpression did not alter NK cell development or NK cell–activating and inhibitory receptor expression yet, as in humans, did decrease expression of downstream NK activation targets MAPK and AKT during early cytolysis of tumor target cells. Confocal microscopy revealed that PTEN overexpression disrupts the NK cell’s ability to organize immunological synapse components including decreases in actin accumulation, polarization of the microtubule organizing center, and the convergence of cytolytic granules. In summary, our data suggest that PTEN normally works to limit the NK cell’s PI3K/AKT and MAPK pathway activation and the consequent mobilization of cytolytic mediators toward the target cell and suggest that PTEN is among the active regulatory components prior to human NK cells transitioning from the noncytolytic CD56bright NK cell to the cytolytic CD56dim NK cells.

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“…WNT/β-catenin, RAS/ERK/ MAPK, JAK/STAT, NOTCH), we believe ncRNA may also play a role in the resistance of PI3K inhibitors [194][195][196][197][198][199]. Not surprisingly, more and more researches have suggested that deviant ncRNA expression is powerfully concerned about tumor drug resistance [200][201][202][203][204][205][206][207][208]. Recent studies have indicated potential mechanism of acquired resistance to dual PI3K/mTOR inhibitors, including elevated glycolysis accompanied with depletion of mitochondrial DNA, and upregulated DNA methyltransferases which Reduce PTEN and PPP2R2B expression [209,210].…”

Section: Resistancesmentioning

confidence: 99%

Targeting PI3K in cancer: mechanisms and advances in clinical trials

et al. 2019

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Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling is one of the most important intracellular pathways, which can be considered as a master regulator for cancer. Enormous efforts have been dedicated to the development of drugs targeting PI3K signaling, many of which are currently employed in clinical trials evaluation, and it is becoming increasingly clear that PI3K inhibitors are effective in inhibiting tumor progression. PI3K inhibitors are subdivided into dual PI3K/mTOR inhibitors, pan-PI3K inhibitors and isoform-specific inhibitors. In this review, we performed a critical review to summarize the role of the PI3K pathway in tumor development, recent PI3K inhibitors development based on clinical trials, and the mechanisms of resistance to PI3K inhibition.

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MicroRNA‐221 targeting PI3‐K/Akt signaling axis induces cell proliferation and BCNU resistance in human glioblastoma

Cited by 41 publications

References 28 publications

Downregulation of miR-221/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN

Downregulation of miR-221/222 by a microRNA sponge promotes apoptosis in oral squamous cell carcinoma cells through upregulation of PTEN

PTEN Is a Negative Regulator of NK Cell Cytolytic Function

Targeting PI3K in cancer: mechanisms and advances in clinical trials

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