MicroRNA‑98/PTEN/AKT pathway inhibits cell proliferation and malignant progression of hypopharyngeal carcinoma by MTDH

Wang, Qiwei; Tan, Lijun; Liu, Jiangtao; Zhao, Jianwen; Zhou, Xiaojie; Yu, Tianjiao

doi:10.3892/or.2018.6904

Cited by 7 publications

(10 citation statements)

References 25 publications

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“…Some studies have uncovered the involvement of MTDH in the regulation of the PTEN-AKT signaling pathway. 23,24 We determined whether miR-559 inhibits the output of the PTEN-AKT pathway in GBM cells. MiR-559 mimics and pcDNA3.1 or pcDNA3.1-MTDH were introduced into U251 and T98 cells, and western blot analysis was performed to measure MTDH, p-AKT, and AKT protein amounts.…”

Section: Mir-559 Inhibits Akt In the Pten-akt Pathway In Gbm Cellsmentioning

confidence: 99%

<p>MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin</p>

Yang¹,

Zhang²,

Xu³

et al. 2019

OTT

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Purpose: Several microRNAs (miRNAs) that are aberrantly expressed in glioblastoma multiforme (GBM) play a significant role in GBM formation and progression. The expression profile and functions of miR-559 in GBM remain unclear. Here, we quantified the expression and investigated the involvement of miR-559 in the oncogenicity of GBM cells in vitro and in vivo. Material and methods: Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was carried out to determine miR-559 expression in GBM tissues and cell lines. A series of functional assays was performed to evaluate the effects of miR-559 overexpression on GBM cell proliferation, apoptosis, migration, and invasion in vitro and on GBM tumor growth in vivo. The regulatory mechanisms of miR-559 action in GBM cells were then explored. Results: The expression of miR‑559 was lower in GBM tissues and cell lines and significantly correlated with the Karnofsky performance score and tumor size among patients with GBM. Exogenous miR‑559 expression inhibited GBM cell proliferation, migration, and invasion and promoted apoptosis. MiR-559 overexpression decreased tumor growth in vivo. Mechanistic experiments confirmed metadherin ( MTDH ) as a direct target gene of miR-559 in GBM. Silencing of MTDH induced effects similar to those of miR-559 upregulation in GBM cells, whereas MTDH expression restoration attenuated the antitumor effects of miR‑559 in GBM cells. Protein kinase B (AKT) in the phosphatase and tensin homolog (PTEN)–AKT signaling pathway was found to be deactivated in GBM cells after upregulation of miR-559 both in vitro and in vivo. Conclusion: MiR-559 acts as a tumor suppressor in GBM cells in vitro and in vivo, at least in part through the downregulation of MTDH and inhibition of AKT in the PTEN–AKT pathway. Therefore, targeting the miR-559–MTDH axis may be a promising therapeutic strategy for patients with GBM.

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Section: Mir-559 Inhibits Akt In the Pten-akt Pathway In Gbm Cellsmentioning

confidence: 99%

<p>MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin</p>

Yang¹,

Zhang²,

Xu³

et al. 2019

OTT

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“…Phosphatase and tensin homolog (PTEN) has been appreciated as an important tumor suppressor and to oppose phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in human cancers [12]. Accruing works have revealed that PTEN is involved in progression of cancers and negatively correlated with AKT signaling in hypopharyngeal carcinoma, non-small cell lung cancer and esophageal squamous cell carcinoma [13][14][15]. Previous study suggested that loss of PTEN is associated with progression of papillary thyroid cancer [16].…”

mentioning

confidence: 99%

miR-17-5p knockdown inhibits proliferation, autophagy and promotes apoptosis in thyroid cancer via targeting PTEN

Shi¹,

Liu²,

Li³

et al. 2020

neo

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Thyroid cancer is one common endocrine malignancy with various pathological types. MicroRNAs (miRNAs) play essential roles in development, prognosis and treatment of thyroid cancer. However, the role of miR-17-5p in thyroid cancer progression and its mechanism remain poorly understood. The expressions of miR-17-5p and phosphatase and tensin homolog (PTEN) were measured in thyroid cancer tissues and cells by quantitative real-time polymerase chain reaction or western blot. Cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. The protein levels of biomarkers in autophagy or protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway were analyzed by western blot. The interaction between miR-17-5p and PTEN was probed by luciferase activity assay. We found that miR-17-5p expression was elevated and PTEN level was reduced in thyroid cancer tissues and cells compared with their corresponding controls. Knockdown of miR-17-5p or overexpression of PTEN suppressed cell proliferation and autophagy but promoted apoptosis in thyroid cancer cells. PTEN was indicated as a target of miR-17-5p and its interference reversed abrogation of miR-17-5p-mediated inhibition of proliferation and autophagy and increase of apoptosis. Moreover, downregulation of miR-17-5p impeded the activation of AKT/mTOR pathway in thyroid cancer cells, which was attenuated by silencing PTEN. Our data supported that knockdown of miR-17-5p upregulated PTEN expression, therefore leading to suppression of the malignancy of thyroid cancer and inactivation of AKT/mTOR pathway, providing a novel avenue for treatment of thyroid cancer.

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“…However, the regulatory mechanism of MTDH is diverse. Studies have reported that several miRNAs, such as miR-98, miR-182-5p, miR-36645p and miR-384, could exert antitumour effects by targeting MTDH [36][37][38][39] . Sarkar et al 40 revealed that MTDH acted as a bridging factor by connecting NF-κB and CREB binding protein in malignant gliomas.…”

Section: Discussionmentioning

confidence: 99%

mPGES-1/PGE2 promotes the growth of T-ALL cells in vitro and in vivo by regulating the expression of MTDH via the EP3/cAMP/PKA/CREB pathway

Chen

Yang

et al. 2020

Cell Death Dis

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T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive haematological malignancy that is characterized by a high frequency of induction failure and by early relapse. Many studies have revealed that metadherin (MTDH) is highly expressed in a variety of malignant solid tumours and plays an important role in the occurrence and development of tumours. However, the relationship between the expression of MTDH and T-ALL has not yet been reported, and the regulatory factors of MTDH are still unknown. Our previous studies found that mPGES-1/PGE2 was important for promoting the growth of leukaemia cells. In the present study, we found that MTDH was highly expressed in primary T-ALL cells and in the Jurkat cell line. Our results showed that mPGES-1/PGE2 regulates the expression of MTDH through the EP3/cAMP/PKA-CREB pathway in T-ALL cells. Downregulation of MTDH inhibits the growth of Jurkat cells in vitro and in vivo. Our results suggest that MTDH could be a potential target for the treatment of T-ALL.

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MicroRNA‑98/PTEN/AKT pathway inhibits cell proliferation and malignant progression of hypopharyngeal carcinoma by MTDH

Cited by 7 publications

References 25 publications

<p>MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin</p>

<p>MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin</p>

miR-17-5p knockdown inhibits proliferation, autophagy and promotes apoptosis in thyroid cancer via targeting PTEN

mPGES-1/PGE2 promotes the growth of T-ALL cells in vitro and in vivo by regulating the expression of MTDH via the EP3/cAMP/PKA/CREB pathway

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