MMP1, 2, 3, 7, and 9 Gene Polymorphisms and Urinary Cancer Risk: A Meta-Analysis

Liu, Tao; Zuo, Li; Li, Lin; Li, Yin; Yu, Hongyuan; Jing, Hongwei; Liu, Yang; Kong, Chuize

doi:10.1089/gtmb.2015.0123

Cited by 22 publications

(21 citation statements)

References 44 publications

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“…Among them, MMP2 primarily hydrolyzes type IV collagen, the major structural component of the basement membrane [ 44 ]. Many studies have verified that MMP2 is critical in mediating BC invasion [ 36 , 45 ], but the maintenance of MMP2 abundance has not been well studied. Based on our results here, overexpression of PHLPP2 significantly decreases MMP2 protein level, which is known to regulate BC cell invasion.…”

Section: Discussionmentioning

confidence: 99%

PHLPP2 stabilization by p27 mediates its inhibition of bladder cancer invasion by promoting autophagic degradation of MMP2 protein

et al. 2018

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Pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a tumor suppressor that catalyzes the de-phosphorylation of the AGC kinases, while p27 acts as a tumor suppressor that regulates cell cycle, apoptosis, and cell motility. Our previous studies have identified that PHLPP2 participates in inhibition of transformation of human bronchial epithelial cells following lung carcinogen B[a]P/B[a]PDE exposure. However, nothing was known about the association of p27 with regulation of PHLPP2 expression and the role of PHLPP2 in bladder cancer (BC) invasion. In our current studies, we demonstrated that PHLPP2 inhibited BC invasion through promoting MMP2 degradation via p62-mediated autophagy; and p27 expression was able to stabilize PHLPP2 protein by inhibiting protein degradation of Hsp90, which could directly bind to PHLPP2 and protect it from degradation. More in-depth studies discovered that stabilization of Hsp90 by p27 was mediated by calpain1 proteolysis system, whereas p27 inhibited calpain1 gene transcription by attenuating Jak1/Stat1 cascade in human invasive BC cells. Collectively, we for the first time revealed PHLPP2 downregulation in BCs and its participating in promotion of BC invasion, as well as novel role of p27 and mechanisms underlying its regulation of PHLPP2 protein degradation through Hsp90-dependent manner. Our findings improve our understanding of p27 and PHLPP2 roles and their crosstalk in regulation of BC invasion, which further contributes to improve the current strategy for invasive bladder cancer therapy.

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Section: Discussionmentioning

confidence: 99%

PHLPP2 stabilization by p27 mediates its inhibition of bladder cancer invasion by promoting autophagic degradation of MMP2 protein

et al. 2018

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“…MMPs are zinc metalloproteases that degrade ECM collagens, which are important in tissue remodeling and repair during development and inflammation [ 19 ]. Among the MMP genes, gelatinase A, encoded by the MMP2 gene, has been specifically correlated to tumor pathogenesis [ 20 , 21 ]. Furthermore, the MMP2 promoter contains several cis-acting regulatory elements, which modulate MMP2 expression through transcription factors, such as p53 and Sp1 [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

The MMP2 rs243865 polymorphism increases the risk of prostate cancer: A meta-analysis

Liu

et al. 2017

Oncotarget

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Prostate cancer is a common cancer in men. However, the association between the rs243865 single-nucleotide polymorphisms in the matrix metalloproteinase 2 gene (MMP2) and the risk for prostate cancer is inconclusive. We searched the PubMed, EMBASE, Cochrane Library, and the Chinese CNKI and WANFANG databases for the relevant literature. Data were extracted and pooled results were estimated from odds ratios (OR) with 95% confidence intervals (95% CIs). The quality of included studies was assessed, and publication bias of all included studies was examined. A total five studies involving 1895 patients with prostate cancer and 1918 controls were included. There was a significant association between rs243865 polymorphisms and higher risk of prostate cancer in the co-dominant model, dominant model, and allele model (CC vs. CT+TT, OR: 1.60, 95% CI: 1.22–2.11, P = 0.001; CC vs. CT, OR: 1.80, 95% CI: 1.34–2.42, P < 0.001; C vs. T, OR: 1.32, 95% CI: 1.05–1.66, P = 0.016, respectively). However, there was no significant difference between the co-recessive model and recessive model. Our meta-analysis results suggest that MMP2 rs243865 polymorphisms are significantly associated with higher risk of prostate cancer.

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“…15 These results are the opposite to the previously mentioned Asian based metaanalysis. 14 According to the db SNP and HapMap data on rs243865 frequency in genetically different populations, the C allele is more common in Caucasian populations. That can perhaps contribute to the different results in different studied populations.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Štrbac¹,

Goričar²,

Dolžan³

et al. 2018

Radiology and Oncology

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Patients and methods. The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%-75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).Results. Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44-1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35-0.86; P = 0.009).None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma.Conclusions. The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.

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MMP1, 2, 3, 7, and 9 Gene Polymorphisms and Urinary Cancer Risk: A Meta-Analysis

Cited by 22 publications

References 44 publications

PHLPP2 stabilization by p27 mediates its inhibition of bladder cancer invasion by promoting autophagic degradation of MMP2 protein

PHLPP2 stabilization by p27 mediates its inhibition of bladder cancer invasion by promoting autophagic degradation of MMP2 protein

The MMP2 rs243865 polymorphism increases the risk of prostate cancer: A meta-analysis

Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

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