Matrix metallopeptidase 9 targeted by hsa‐miR‐494 promotes silybin‐inhibited osteosarcoma

Sun, Tianhao; Cheung, Kelvin; Liu, Zhili; Leung, Frankie; Lu, William W.

doi:10.1002/mc.22753

Cited by 14 publications

(12 citation statements)

References 38 publications

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“…Therefore, future studies will determine whether miR-494 targets astrocytes or microglia in addition to directly influencing neuronal cell death. MiR-494 likely has other targets in stroke beyond HDAC3, such as other proven targets including matrix metalloproteinase-9 (MMP-9), 26 PTEN/Akt, 27 cell cycle regulator p27, 28 and DNA damage repair-related RAD23B, 29 all of which are involved in cerebral ischemic brain injury. Further mechanistic studies are warranted to carefully dissect the complex pathways for miR-494 in stroke and neuronal death.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of histone deacetylase 3 by MiR-494 alleviates neuronal loss and improves neurological recovery in experimental stroke

Zhao

Zhang

et al. 2019

J Cereb Blood Flow Metab

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HDAC3 is an essential negative regulator of neuronal plasticity and memory formation. Although a chemical inhibitor has been invented, little is known about its endogenous modulators. We explored whether miR-494 affects HDAC3-mediated neuronal injury following acute ischemic stroke. A substantial increase in plasma miR-494 was detected in AIS patients and was positively associated with the mRS at one year after symptom onset. The miR-494 levels were transiently increased in the infarcted brain tissue of mice. In contrast, miR-494 levels were reduced in neurons but increased in the medium after OGD. Intracerebroventricular injection of miR-494 agomir reduced neuronal apoptosis and infarct volume at the acute stage of MCAO, promoted axonal plasticity and long-term outcomes at the recovery stage, suppressed neuronal ataxin-3 and HDAC3 expression and increased acetyl-H3K9 levels in the ipsilateral hemisphere. In vitro studies confirmed that miR-494 posttranslationally inhibited HDAC3 in neurons and prevented OGD-induced neuronal axonal injury. The HDAC3 inhibitor increased acetyl-H3K9 levels and reversed miR-494 antagomir-aggravated acute cerebral ischemic injury, as well as brain atrophy and long-term functional recovery. These results suggest that miR-494 may serve as a predictive biomarker of functional outcomes in AIS patients and a potential therapeutic target for the treatment of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Inhibition of histone deacetylase 3 by MiR-494 alleviates neuronal loss and improves neurological recovery in experimental stroke

Zhao

Zhang

et al. 2019

J Cereb Blood Flow Metab

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“…MMP9, a member of the MMPs, plays an important role in extracellular matrix remodeling and angiogenesis, which have been linked to the aggressiveness of gynecological tumors such as cervical cancer ( Rauvala et al, 2006 ), endometrial Osteosarcoma . ( Sun et al, 2018 ) and ovarian carcinoma ( Brun et al, 2008 ; Ozalp et al, 2003 ; Schmalfeldt et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

High expression level of MMP9 is associated with poor prognosis in patients with clear cell renal carcinoma

Niu

Wang

et al. 2018

PeerJ

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Matrix metallopeptidase 9 (MMP9) was found to be associated with tumor aggressiveness. In this study, we focused on the correlation between MMP9 expression and clear cell renal carcinoma (ccRCC). Through the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) database and immunohistochemical (IHC) staining, we observed that compared with adjacent normal renal tissues, in ccRCC tissues the mRNA and protein levels of MMP9 were enhanced, and the mRNA levels of GTP-binding protein smg p21B(RAP1B), B rapidly accelerated fibrosarcoma (RAF), methyl ethyl ketone2 (MEK2), extracellular regulated protein kinases1 (ERK1), ERK2, v-ets avian erythroblastosis virus E26 oncogene homolog1 (ETS1) and ETS2 also increased. The Kaplan–Meier survival analysis suggested that high MMP9 expression was an unfavorable prognostic biomarker for ccRCC patients. Our results indicated that the increased expression level of MMP9 in ccRCC may be due to the activation of the Mitogen-activated protein kinases (MAPK)/ERK signaling pathway, and MMP9 may be an attractive target for ccRCC therapy.

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“…For the invasion and dissemination of tumor cells MMPs‐mediated extracellular matrix degradation is required . MMP9 is among the major players of MMP family and has been linked to invasiveness and aggressiveness of cancer cells . The modulation of MMP9 expression by ZEB2 was previously reported in gastric cancers .…”

Section: Discussionmentioning

confidence: 96%

ETS1 is coexpressed with ZEB2 and mediates ZEB2‐induced epithelial‐mesenchymal transition in human tumors

Yalim-Camci

Balçık-Erçin

Çetįn

et al. 2019

Molecular Carcinogenesis

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Epithelial‐mesenchymal transition (EMT) is an embryonic program that is reactivated in cancer and regulates the invasion and metastasis of tumor cells. Zinc finger E‐box binding homeobox 2 (ZEB2) induces EMT by upregulating matrix metalloproteinases (MMP), yet MMP genes lack ZEB2 binding motif in their promoters. Recently, expression of MMPs was associated to the activation of ETS1 transcription factor; however, a link between ZEB2 and ETS proto‐oncogene 1, transcription factor (ETS1) remains to be elucidated. Hence, we investigated the transcriptional regulation of ETS1 by ZEB2 after our initial observation that ZEB2 and ETS1 are coexpressed in hepatocellular carcinoma cells (HCCs). Chromatin immunoprecipitation and luciferase reporter assays clearly showed that ZEB2 binds to E‐box sequences on the promoter of ETS1. Elevated expression of ETS1 was found in DLD‐ZEB2 and A431‐ZEB2 inducible systems, and knockdown of ZEB2 caused an explicit downregulation of ETS1 in shZEB2‐SNU398 and shZEB2‐SK‐HEP‐1 cells. Repression of ETS1 expression in ZEB2‐induced conditions substantially impaired the migration and invasive capacities of DLD1 cells. Mechanistically, knockdown of ETS1 in ZEB2‐expressing cells resulted in the downregulation of established ZEB2 targets TWIST and MMP9. Correlation analyses in HCC lines, cancer complementary DNA arrays, and The Cancer Genome Atlas RNA‐sequencing data set revealed that ZEB2 and ETS1 are coexpressed, and their expressions in human tumors show a highly significant positive correlation. Our results demonstrated that ZEB2 acts as an upstream regulator of ETS1 and, in turn, ETS1 maintains ZEB2‐induced EMT. These findings add another level of complexity to the understanding of ZEB2 in the invasion and metastasis of cancer cells, and put ZEB2/ETS1 axis as a novel therapeutic target in human malignancies.

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Matrix metallopeptidase 9 targeted by hsa‐miR‐494 promotes silybin‐inhibited osteosarcoma

Cited by 14 publications

References 38 publications

Inhibition of histone deacetylase 3 by MiR-494 alleviates neuronal loss and improves neurological recovery in experimental stroke

Inhibition of histone deacetylase 3 by MiR-494 alleviates neuronal loss and improves neurological recovery in experimental stroke

High expression level of MMP9 is associated with poor prognosis in patients with clear cell renal carcinoma

ETS1 is coexpressed with ZEB2 and mediates ZEB2‐induced epithelial‐mesenchymal transition in human tumors

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