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MiR-19a enhances cell proliferation, migration, and invasiveness through enhancing lymphangiogenesis by targeting thrombospondin-1 in colorectal cancer.
Biochemistry and Cell Biology ( IF 2.4 ) Pub Date : 2019-06-14 , DOI: 10.1139/bcb-2018-0302
Qian Yin 1, 1 , Pei-Pei Wang 1, 1 , Rui Peng 1, 1 , Hang Zhou 1, 1
Affiliation  

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.

中文翻译:

MiR-19a通过靶向大肠癌中的血小板反应蛋白1来增强淋巴管生成,从而增强细胞增殖,迁移和侵袭性。

大肠癌(CRC)是具有高死亡率和高发病率的毁灭性疾病,人们对CRC中miR-19a的潜在机制了解甚少。在我们的研究中,使用双荧光素酶报告基因分析评估miR-19a与血小板反应蛋白1(THBS1)的结合。分别使用MTT,伤口愈合和Transwell分析评估细胞活力,迁移和侵袭性。使用具有人类淋巴管内皮细胞(HLEC)的试管形成测定法来评估淋巴管生成,并使用肿瘤异种移植测定法来测量肿瘤的生长。结果表明,在CRC组织和细胞中miR-19a上调,而THBS1下调。使用miR-19a抑制剂可抑制生存,迁移和侵袭性,并抑制基质金属肽酶9(MMP-9)和血管内皮生长因子C(VEGFC)的表达。进一步的机理研究确定THBS1是miR-19a的直接靶标。THBS1沉默减弱了miR-19a抑制剂诱导的上述抑制作用。此外,miR-19a抑制剂通过靶向THBS1-MMP-9 / VEGFC信号通路抑制了HLEC的迁移和成管能力。miR-19a的抑制作用还可以抑制体内肿瘤的生长和淋巴管的形成。总之,miR-19a抑制可抑制CRC细胞的活力,迁移和侵袭性,并抑制HLEC的迁移和成管能力,并且进一步通过靶向THBS1抑制体内肿瘤的生长和淋巴管的形成。进一步的机理研究确定THBS1是miR-19a的直接靶标。THBS1沉默减弱了miR-19a抑制剂诱导的上述抑制作用。此外,miR-19a抑制剂通过靶向THBS1-MMP-9 / VEGFC信号通路抑制了HLEC的迁移和成管能力。miR-19a的抑制作用还可以抑制体内肿瘤的生长和淋巴管的形成。总之,miR-19a抑制可抑制CRC细胞的活力,迁移和侵袭性,并抑制HLEC的迁移和成管能力,并且进一步通过靶向THBS1抑制体内肿瘤的生长和淋巴管的形成。进一步的机理研究确定THBS1是miR-19a的直接靶标。THBS1沉默减弱了miR-19a抑制剂诱导的上述抑制作用。此外,miR-19a抑制剂通过靶向THBS1-MMP-9 / VEGFC信号通路抑制了HLEC的迁移和成管能力。miR-19a的抑制作用还可以抑制体内肿瘤的生长和淋巴管的形成。总之,miR-19a抑制可抑制CRC细胞的活力,迁移和侵袭性,并抑制HLEC的迁移和成管能力,并且进一步通过靶向THBS1抑制体内肿瘤的生长和淋巴管的形成。miR-19a抑制剂通过靶向THBS1-MMP-9 / VEGFC信号通路抑制了HLEC的迁移和成管能力。miR-19a的抑制作用还可以抑制体内肿瘤的生长和淋巴管的形成。总之,miR-19a抑制可抑制CRC细胞的活力,迁移和侵袭性,并抑制HLEC的迁移和成管能力,并且进一步通过靶向THBS1抑制体内肿瘤的生长和淋巴管的形成。miR-19a抑制剂通过靶向THBS1-MMP-9 / VEGFC信号通路抑制了HLEC的迁移和成管能力。miR-19a的抑制作用还可以抑制体内肿瘤的生长和淋巴管的形成。总之,miR-19a抑制可抑制CRC细胞的活力,迁移和侵袭性,并抑制HLEC的迁移和成管能力,并且进一步通过靶向THBS1抑制体内肿瘤的生长和淋巴管的形成。
更新日期:2019-11-01
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