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MiR-19a enhances cell proliferation, migration, and invasiveness through enhancing lymphangiogenesis by targeting thrombospondin-1 in colorectal cancer.
- Source :
-
Biochemistry and cell biology = Biochimie et biologie cellulaire [Biochem Cell Biol] 2019 Dec; Vol. 97 (6), pp. 731-739. Date of Electronic Publication: 2019 Jun 14. - Publication Year :
- 2019
-
Abstract
- Colorectal cancer (CRC) is a devastating disease with high mortality and morbidity, and the underlying mechanisms of miR-19a in CRC are poorly understood. In our study, dual-luciferase reporter assays were used to evaluate the binding of miR-19a with thrombospondin-1 (THBS1). Cell viability, migration, and invasiveness were assessed using MTT, wound healing, and Transwell assays, respectively. Tube-formation assays with human lymphatic endothelial cells (HLECs) were used to evaluate lymphangiogenesis, and tumor xenograft assays were used to measure tumor growth. The results showed that miR-19a was up-regulated and THBS1 was down-regulated in CRC tissues and cells. Applying an inhibitor of miR-19a suppressed survival, migration, and invasiveness, and inhibited the expression of matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor C (VEGFC). Further mechanistic study identified that THBS1 is a direct target of miR-19a. THBS1 silencing attenuated the above-mentioned suppressive effects induced with the miR-19a inhibitor. Furthermore, the miR-19a inhibitor suppressed the migration and tube-formation abilities of HLECs via targeting the THBS1-MMP-9/VEGFC signaling pathway. And the inhibition of miR-19a also suppressed tumor growth and lymphatic tube formation in vivo. In conclusion, miR-19a inhibition suppresses the viability, migration, and invasiveness of CRC cells, and suppresses the migration and tube-formation abilities of HLECs, and further, inhibits tumor growth and lymphatic tube formation in vivo via targeting THBS1.
- Subjects :
- Animals
Cell Movement genetics
Cell Proliferation genetics
Cell Survival genetics
Cells, Cultured
Colorectal Neoplasms metabolism
Colorectal Neoplasms pathology
Female
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neoplasms, Experimental genetics
Neoplasms, Experimental metabolism
Neoplasms, Experimental pathology
Neoplasms, Experimental therapy
Thrombospondin 1 metabolism
Wound Healing
Colorectal Neoplasms genetics
Colorectal Neoplasms therapy
Lymphangiogenesis genetics
MicroRNAs genetics
Thrombospondin 1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1208-6002
- Volume :
- 97
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biochemistry and cell biology = Biochimie et biologie cellulaire
- Publication Type :
- Academic Journal
- Accession number :
- 31199884
- Full Text :
- https://doi.org/10.1139/bcb-2018-0302