High expression of matrix metalloproteinases 16 is associated with the aggressive malignant behavior and poor survival outcome in colorectal carcinoma

Wu, Shengwen; Ma, Cong-Chao; Shan, Shaoyin; Zhou, Lei; Li, Wenhui

doi:10.1038/srep46531

Cited by 15 publications

(13 citation statements)

References 19 publications

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“…A semiquantitative scoring system 14 was used to evaluate both staining intensity (0, no staining; 1+, weak staining; 2+, moderate staining; 3+, strong staining) and the percentage of stained cells (0, <5%; 1, 5%-25%; 2, 26%-50%; 3, 51%-75%; and 4, >75%). The scores for staining intensity and percentage of positive cells were then multiplied to generate the immunoreactivity score for each case15, 16. All cases were sorted into two groups according to the immunoreactivity score.…”

Section: Methodsmentioning

confidence: 99%

The KLF14 Transcription Factor Regulates Glycolysis by Downregulating LDHB in Colorectal Cancer

Wu¹,

Yuan²,

Chen³

et al. 2019

Int. J. Biol. Sci.

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The Krüppel-like transcription factor 14 (KLF14) is a critical regulator of a wide array of biological processes. However, the role of KLF14 in colorectal cancer (CRC) isn't fully investigated. This study aimed to explore the clinicopathological significance and potential role of KLF14 in the carcinogenesis and progression of CRC. A tissue microarray consisting of 185 samples from stage I-III CRC patients was adopted to analyze the correlation between KLF14 expression and clinicopathological parameters, as well as overall survival (OS) and disease-free survival (DFS). The underlying mechanisms of altered KLF14 expression on glycolysis were studied using in vitro and patients' samples. The results showed that KLF14 expression was downregulated in CRC than their normal controls. Low KLF14 expression correlated with advanced T stage (P< 0.001) and N stage (P= 0.040), and larger tumor size (P= 0.008). Lost KLF14 expression implied shorter OS and DFS after colectomy in both univariate and multivariate survival analysis (P<0.05). Experimentally, restore KLF14 expression significantly decreased the rate of glycolysis both in vitro and in patients' sample. Mechanically, KLF14 regulated glycolysis by downregulating glycolytic enzyme LDHB. Collectively, KLF14 is a novel prognostic biomarker for survival in CRC, and downregulation of KLF14 in CRC prompts glycolysis by target LDHB. Hence, KLF14 could constitute potential prognostic predictors and therapeutic targets for CRC.

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Section: Methodsmentioning

confidence: 99%

The KLF14 Transcription Factor Regulates Glycolysis by Downregulating LDHB in Colorectal Cancer

Wu¹,

Yuan²,

Chen³

et al. 2019

Int. J. Biol. Sci.

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“…A semiquantitative scoring system 16 was used to evaluate both staining intensity (0, no staining; 1+, weak staining; 2+, moderate staining; 3+, strong staining) and the percentage of stained cells (0, <5%; 1, 5%-25%; 2, 26%-50%; 3, 51%-75%; and 4, >75%). The scores for staining intensity and percentage of positive cells were then multiplied to generate the immunoreactivity score for each case 17 , 18 . All cases were sorted into two groups according to the immunoreactivity score.…”

Section: Methodsmentioning

confidence: 99%

“…Fifteen paired liver metastases, primary cancer tissues, and their normal control were collected immediately stored in RNA-later at -80°C after they resected from synchronous colorectal cancer liver metastases patients. NOTCH4 mRNA levels were analyzed using a real-time PCR assay as previously described 18 . The total RNA from tissues was extracted using the TRIzol reagent (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions, and reversely transcripted to cDNA with PrimeScript™ RT Master Mix (Perfect Real Time) kit (RR036A, Takara) based on the manufacturer's instruction.…”

Section: Methodsmentioning

confidence: 99%

NOTCH4 Is a Novel Prognostic Marker that Correlates with Colorectal Cancer Progression and Prognosis

Wu¹,

Chen²,

Li³

et al. 2018

J. Cancer

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Notch family plays vital role in carcinogenesis and progression of various cancer, however, its clinical significance and prognostic value in colorectal cancer isn't fully investigated. In present study, we first investigated the NOTCH4 expression in The Cancer Genome Atlas (TCGA) (n=361) and GSE39582 (n=474) database and then validated with our own database (n=248). The transcriptional and protein levels of NOTCH4 were evaluated by RT-PCR and immunohistochemistry study, respectively. Univariate and multivariate survival analyses were performed to explore the relationship between various prognostic factors and survival outcomes. In the univariate analysis, NOTCH3 and NOTCH4 were significantly correlated with prognosis in TCGA and GSE39582 database, respectively (P<0.05). For NOTCH3 has been studied in CRC, we chosen NOTCH4 for further study. NOTCH4 mRNA was higher in liver metastases than their primary colorectal cancer or normal mucosa. Increased NOTCH4 levels significantly correlated with advanced N stage (P= 0.002), M stage (P= 0.002), lymphovascular invasion (P= 0.026), and CEA status (P= 0.030). Patients with high NOTCH4 expression had shorter 5-year disease-free survival (DFS) (HR 6.809; 95% CI 3.334-13.904; P< 0.001) and overall survival (OS) (HR 6.476; 95% CI 3.307-12.689; P<0.001) than those with low NOTCH4 expression. Multivariate survival analysis demonstrated that NOTCH4 was an independent prognostic biomarker for both DFS (HR 7.848; 95% CI 3.777-16.308; P<0.001) and OS (HR 5.323; 95% CI 2.668-10.623; P<0.001).Collectively, NOTCH4 may play critical role in colorectal cancer progression and could serve as a novel biomarker to predict survival after colectomy.

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“…MMP16 is a major mediator of pericellular matrix proteolysis and regulates remodeling of the ECM, either directly through proteolysis or indirectly through the activation of other enzymes (Bao et al, 2013). In recent studies, MMP16 expression was investigated in a range of cancers (Rak et al, 2017; Roth, Kalev‐Altman, Monsonego‐Ornan, & Sela‐Donenfeld, 2017; Wu, Ma, Shan, Zhou, & Li, 2017), but its role in lung development is poorly defined. The ability of MMP16 to localize on the cell membrane and activate pro‐ MMP2 has received wide attention.…”

Section: Discussionmentioning

confidence: 99%

A protective polymorphism inMMP16, improved blood gas levels, and chronic obstructive pulmonary diseases: Family and two population‐based studies

et al. 2020

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The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole‐genome sequencing, and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C) and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract‐treated 16HBE cells compared with controls. This was also shown by bioinformatics analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared with those carrying CT and TT. Treatment with hsa‐miR‐576‐5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO2, and PO2 in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring interaction with hsa‐miR‐576‐5p, leading to reduced MMP16 expression and improved blood gas levels.

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High expression of matrix metalloproteinases 16 is associated with the aggressive malignant behavior and poor survival outcome in colorectal carcinoma

Cited by 15 publications

References 19 publications

The KLF14 Transcription Factor Regulates Glycolysis by Downregulating LDHB in Colorectal Cancer

The KLF14 Transcription Factor Regulates Glycolysis by Downregulating LDHB in Colorectal Cancer

NOTCH4 Is a Novel Prognostic Marker that Correlates with Colorectal Cancer Progression and Prognosis

A protective polymorphism inMMP16, improved blood gas levels, and chronic obstructive pulmonary diseases: Family and two population‐based studies

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