Role of microRNA-mediated MMP regulation in the treatment and diagnosis of malignant tumors

Li, Liqin; Li, Heng

doi:10.4161/cbt.25936

Cited by 54 publications

(41 citation statements)

References 106 publications

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“…There are more and more miRNAs have been involved in the regulation of cancer metastasis [27], and there have been considerable interest in the posttranscriptional regulation of MMPs via miRNAs [28]. Therefore, we hypothesized that miRNA may be involved in CTGF-mediated MMPs expression and tumor metastasis in human osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d

Tsai

Huang

et al. 2014

Oncotarget

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Osteosarcoma, the most common primary malignant bone tumor, shows potent capacity for local invasion and distant metastasis. Connective tissue growth factor (CTGF/CCN2), a secreted protein, binds to integrins, modulates invasive behavior of certain human cancer cells. Effect of CTGF in metastasis of human osteosarcoma is unknown. We found overexpression of CTGF increasing matrix metalloproteinases (MMPs)-2 and MMP-3 expression as well as promoting cell migration. MicroRNA (miRNA) analysis of CTGF-overexpressed osteosarcoma versus control cells probed mechanisms of CTGF-mediated promotion of migration. Among miRNAs regulated by CTGF, miR-519d was most downregulated after CTGF treatment. Co-transfection with miR-519d mimic reversed CTGF-mediated MMPs expression and cell migration. Also, MEK and ERK inhibitors or mutants reduced CTGF-increased cell migration and miR-519d suppression. By contrast, knockdown of CTGF diminished lung metastasis in vivo. Clinical samples indicate CTGF expression as linked with clinical stage and tumor metastasis. Taken together, data show CTGF elevating MMPs expression and subsequently promoting tumor metastasis in human osteosarcoma, down-regulating miR-519d via MEK and ERK pathways, making CTGF a new molecular therapeutic target in osteosarcoma metastasis.

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Section: Introductionmentioning

confidence: 99%

CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d

Tsai

Huang

et al. 2014

Oncotarget

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“…Similarly, a strong MMP2 and weak TIMP2 immunostaining has been reported as significant prognostic marker of poor survival in EC patients (10,34). MMP2 has been demonstrated to play a crucial role in the remodeling of the collagenous ECM by degrading a broad spectrum of ECM molecules, including: collagen types I, IV, V, VII, X, and IX, elastin, fibronectin, aggrecan, vitronectin, and laminin (23). Furthermore, it has been shown to modulate tumor growth factor-beta (TGF-β) activity by cleaving latent form of TGF-β and releasing inactive TGF-β precursor that is sequestered by ECM (35).…”

Section: Discussionmentioning

confidence: 99%

“…Over the past decade, the fundamental role of miRNAs in endometrial tumorigenesis has been established (19). Furthermore, several miRNAs have been demonstrated to directly or indirectly regulate the expression of MMPs in EC cells (20)(21)(22)(23). In our previous study we found that a reduced level of miR-410 corresponded to an increased expression of MMP14 in EC samples (24).…”

Section: Abstract Background/aim: the Post-transcriptional Regulatiomentioning

confidence: 99%

“…However, pharmacological MMPs inhibitors have failed in multiple clinical trials (23,47). Although there are many factors possibly contributing to the failure of MMP inhibitors in the clinic, among the most frequently discussed reasons are the high structural homology at the active site shared by proteases of this family and their overlapping specificity (48).…”

Section: Cancer Genomics and Proteomicsmentioning

confidence: 99%

“…Moreover, MMPs are involved in a variety of biological processes other than tumor development, and therefore the design of MMP inhibitors that are highly selective and have low side effect profiles seems to be particularly challenging. In comparison to small inhibitor molecules, miRNAs can target MMPs more selectively without the interference of the structural similarities of MMP catalytic domains (23). signaling pathways critical for a malignant tumor behavior (49).…”

Section: Cancer Genomics and Proteomicsmentioning

confidence: 99%

See 2 more Smart Citations

Post-transcriptional Regulation of MMP16 and TIMP2 Expression via miR-382, miR-410 and miR-200b in Endometrial Cancer

Rak

Mehlich

Garbicz

et al. 2017

CGP

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Transforming growth factor‐β, matrix metalloproteinases, and urokinase‐type plasminogen activator interaction in the cancer epithelial to mesenchymal transition

Santibáñez

Obradović

Кукољ

et al. 2017

Developmental Dynamics

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Transforming growth factor-β (TGF-β) is a pleiotropic factor that acts as a tumor suppressor in the early stages, while it exerts tumor promoting activities in advanced stages of cancer development. One of the hallmarks of cancer progression is the capacity of cancer cells to migrate and invade surrounding tissues with subsequent metastasis to different organs. Matrix metalloproteinases (MMPs) together with urokinase-type plasminogen activator (uPA) and its receptor (uPAR), whose main original function described is the proteolytic degradation of the extracellular matrix, play key cellular roles in the enhancement of cell malignancy during cancer progression. TGF-β tightly regulates the expression of several MMPs and uPA/uPAR in cancer cells, which in return can participate in TGF-β activation, thus contributing to tumor malignancy. TGF-β is one of the master factors in the induction of cancer-associated epithelial to mesenchymal transition (EMT), and recently both MMPs and uPA/uPAR have also been shown to be implicated in the cancer-associated EMT process. In this review, we analyze the main molecular mechanisms underlying MMPs and uPA/uPAR regulation by TGF-β, as well as their mutual implication in the development of EMT in cancer cells. Developmental Dynamics 247:382-395, 2018. © 2017 Wiley Periodicals, Inc.

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Role of microRNA-mediated MMP regulation in the treatment and diagnosis of malignant tumors

Cited by 54 publications

References 106 publications

CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d

CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d

Post-transcriptional Regulation of MMP16 and TIMP2 Expression via miR-382, miR-410 and miR-200b in Endometrial Cancer

Transforming growth factor‐β, matrix metalloproteinases, and urokinase‐type plasminogen activator interaction in the cancer epithelial to mesenchymal transition

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