지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.1
- 수록면
- 217 - 223 (7page)
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초록· 키워드
오류제보하기
Matrix metalloproteinases (MMPs) are zincdependent endopeptidases that remodel and degrade the extracellular matrix. Of various MMPs, MMP-2 plays an important role in tumor metastasis. Recently, microRNAs with pro- or anti-metastatic effects were collectively referred to as metastamiRs. We screened 215 human miRNA mimics for modulators of MMP-2 activities in HT- 1080 cells, and found that miR-105 and miR-128 promote MMP-2 activities. Bioinformatics analysis predicted that miR-105 and miR-128 both bind to the 30 untranslated region (UTR) of TIMP-2, an inhibitor of MMP-2 activities. This prediction was verified by reduced luciferase activity in HT-1080 cells co-transfected with miR-105 or miR-128 mimics and plasmids encoding luciferase fused to 30 UTR of TIMP2. In addition, Western blotting showed that transfection of HT-1080 cells with miR-105 or miR-128 suppressed TIMP-2 levels and enhanced levels of MT1- MMP, an activator of MMP-2 activities. The mechanism by which miR-128 upregulates MT1-MMP was determined to be downregulation of PRKD1, an inhibitor of MT1- MMP, at least in part. Cell invasion assays using Matrigel demonstrated that HT-1080 cells transfected with miR-105 or miR-128 are more invasive as compared to control cells. Taken together, these findings show that miR-105 and miR-128 are metastamir promoting MMP-2 activities via simultaneously downregulating TIMP-2 and upregulating MT1-MMP, and may provide a platform for the development of therapeutics against metastasis.
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참고문헌 (41)
참고문헌 신청
Akhtar N / 2010 / miRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes / Arthritis Rheumatol 62:1361~1371
Bartel DP / 2009 / miRNAs: target recognition and regulatory functions / Cell 136:215~233
Benakanakere MR / 2009 / Modulation of TLR2 protein expression by miR-105 in human oral keratinocytes / J Biol Chem 284:23107~23115
Benet M / 2012 / Wild type N-ras displays antimalignant properties, in part by downregulating decorin / J Cell Physiol 227:2341~2351
Caterina JJ / 2000 / Inactivating mutation of the mouse tissue inhibitor of metalloproteinases- 2(Timp-2) gene alters proMMP-2 activation / J Biol Chem 275:26416~26422
Bartel DP / 2009 / miRNAs: target recognition and regulatory functions / Cell 136:215~233
Benakanakere MR / 2009 / Modulation of TLR2 protein expression by miR-105 in human oral keratinocytes / J Biol Chem 284:23107~23115
Benet M / 2012 / Wild type N-ras displays antimalignant properties, in part by downregulating decorin / J Cell Physiol 227:2341~2351
Caterina JJ / 2000 / Inactivating mutation of the mouse tissue inhibitor of metalloproteinases- 2(Timp-2) gene alters proMMP-2 activation / J Biol Chem 275:26416~26422
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