Mdig, a lung cancer-associated gene, regulates cell cycle progression through p27KIP1

Ma, Dan; Guo, Dan; Li, Wei; Zhao, Hongwen

doi:10.1007/s13277-015-3397-z

Cited by 8 publications

(9 citation statements)

References 34 publications

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“…Multiple oncogenic factors including Skp2 [197] and Mdig [198] inhibiting p27 activation by accelerating its degradation, leading to higher cytoplasmic p27 expression, indicating poorer chemosensitivity and long-term survival among patients of non-small cell lung cancer [199]. Similarly, repressed p27 viability is likewisely identified as an inevitable pusher of neoplastic transformation in prostate.…”

Section: Functions Of Ampk Signaling Components In Tumorigenesismentioning

confidence: 99%

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Cheng

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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AMP-activated protein kinase (AMPK) is a ubiquitously expressed metabolic sensor among various species. Specifically, cellular AMPK is phosphorylated and activated under certain stressful conditions, such as energy deprivation, in turn to activate diversified downstream substrates to modulate the adaptive changes and maintain metabolic homeostasis. Recently, emerging evidences have implicated the potential roles of AMPK signaling in tumor initiation and progression. Nevertheless, a comprehensive description on such topic is still in scarcity, especially in combination of its biochemical features with mouse modeling results to elucidate the physiological role of AMPK signaling in tumorigenesis. Hence, we performed this thorough review by summarizing the tumorigenic role of each component along the AMPK signaling, comprising of both its upstream and downstream effectors. Moreover, their functional interplay with the AMPK heterotrimer and exclusive efficacies in carcinogenesis were chiefly explained among genetically altered mice models. Importantly, the pharmaceutical investigations of AMPK relevant medications have also been highlighted. In summary, in this review, we not only elucidate the potential functions of AMPK signaling pathway in governing tumorigenesis, but also potentiate the future targeted strategy aiming for better treatment of aberrant metabolism-associated diseases, including cancer.

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Section: Functions Of Ampk Signaling Components In Tumorigenesismentioning

confidence: 99%

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Cheng

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…It has been found that silencing Mdig/mina53 mRNA expression in A549 lung cancer cells suppresses cell proliferation by delaying the cell cycle transition from G1 to S phase (4,18). These results indicate that Mdig/mina53 might promote cell proliferation by regulating the G1/S transition.…”

Section: Regulation Of Cell Cycle and Cell Proliferationmentioning

confidence: 87%

“…Furthermore, the phosphorylation of p27 KIP1 at its Thr187 site was also inhibited. Importantly, Ma et al (18) also found that upregulation of Mdig/mina53 was accompanied by downregulation of p27 KIP1 in both lung cancer tissues and bronchial stump. This suggests that Mdig/mina53 play an essential role in the cell cycle regulation, cell proliferation and tumor formation by inhibiting p27 KIP1 expression through the phosphorylation of its Thr187 site.…”

Section: Regulation Of Cell Cycle and Cell Proliferationmentioning

confidence: 93%

“…p27 KIP1 , one of cell cyclerelated genes that acts as a tumor suppressor in humans (20), has a negative effect on regulating the cell cycle by inhibiting the G1 phase kinase complexes (such as cyclin e-cdk2 and d-cdk4). Study by Ma et al (18) found that knockdown of Mdig/mina53 in A549 cells can increase the levels of p27 KIP1 on both mRNA and protein, indicating that Mdig/mina53 is a negative regulator for the major cell cycle checkpoint protein, p27 KIP1 . Furthermore, the phosphorylation of p27 KIP1 at its Thr187 site was also inhibited.…”

Section: Regulation Of Cell Cycle and Cell Proliferationmentioning

confidence: 99%

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From biological mechanisms to clinical implications: the role of mineral dust-induced gene in lung cancers

Zhang

Zhao

2017

J. Thorac. Dis.

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“…Many substances can induce mdig expression, such as arsenic (2) and mineral dust (3), among others. It has been reported that mdig is a proto-oncogene that is highly expressed in a variety of tumor cells, where it not only serves as an independent factor leading to tumor formation, but also as a promoter of tumor cell proliferation (1,(4)(5)(6). Mdig/mina53 is a downstream target gene of the transcription factor c-Myc, and is located on chromosome 3 (3q12.1).…”

Section: Introductionmentioning

confidence: 99%

Mdig suppresses epithelial-mesenchymal transition and inhibits the invasion and metastasis of non-small cell lung cancer via regulating GSK-3β/β-catenin signaling

Geng

Jiang

Song

et al. 2017

International Journal of Oncology

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Mineral dust-induced gene (mdig) can inhibit the invasion and metastasis of A549 cells. The main purpose of this study was to explore the molecular mechanism underlying the inhibitory effect of mdig on cell invasion and metastasis. Mdig-knockdown and mdig-overexpressing A549 cells and an mdig-overexpressing human umbilical vein endothelial cell (HUVEC) line were constructed using lentiviral vectors, and western blot analysis was performed to verify the silencing and overexpression of the mdig protein. A Transwell invasion assay was used to detect the invasive abilities of each experimental group, and Transwell migration and scratch assays were used to detect cell migration ability. Western blotting was subsequently conducted to detect the major biochemical indices of the GSK-3β/β-catenin pathway and the protein expression levels and modifications of epithelial‑mesenchymal transition (EMT) transcription factors, as well as changes in the expression levels of EMT molecular markers and intercellular adhesion proteins. The results indicated that overexpression of mdig in A549 cells inhibited cell invasion and metastasis, while silencing of mdig increased the invasive and metastatic properties of cells. The molecular mechanism underlying the effects of mdig downregulation on A549 cell invasion and metastasis was found to involve the inhibition of GSK-3β phosphorylation, which in turn promoted the phosphorylation and destabilization of β-catenin. This was associated with downregulation of the downstream transcription factors slug, snail and ZEB1, thus leading to increased expression levels of epithelial cell markers and upregulation of the intercellular adhesion molecules E-cadherin, claudin‑1, ZO‑1, integrin β1 and integrin β4, which was accompanied by downregulation of the mesenchymal cell markers vimentin and N-cadherin. The HUVECs were used to validate the aforementioned molecular mechanisms and the same conclusions were obtained. The present results indicate that mdig can inhibit the phosphorylation of GSK-3β and promote the phosphorylation and destabilization of β-catenin, in order to suppress the expression of slug, snail, and ZEB1 and the occurrence of EMT, and thereby inhibit the invasion and metastasis of non-small cell lung cancer (NSCLC).

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Mdig, a lung cancer-associated gene, regulates cell cycle progression through p27KIP1

Cited by 8 publications

References 34 publications

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

From biological mechanisms to clinical implications: the role of mineral dust-induced gene in lung cancers

Mdig suppresses epithelial-mesenchymal transition and inhibits the invasion and metastasis of non-small cell lung cancer via regulating GSK-3β/β-catenin signaling

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