Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression

Abstract

The microRNA miR-19a is closely related to tumor formation and development and is a key oncogene. Previous studies have demonstrated that miR-19a is upregulated in multiple cancer types, including colorectal cancer (CRC). However, most of these experiments were performed in vitro, and consequently, the mechanisms underlying the effects of miR-19a on CRC are still unclear. Therefore, in the present study, we investigated the role of miR-19a in the development of solid CRC tumors. We generated KRAS 3'UTR-Mut by deleting the predicted binding site for miR-19a in KRAS, and observed that the expression of a reporter gene containing the KRAS 3'UTR in HCT116 cells was suppressed by miR-19a, while that of a reporter gene with mutant KRAS 3'UTR was unaffected by miR-19a. We observed that high miR-19a levels reduced KRAS expression. In the tube formation assay, overexpression of miR-19a exhibited anti-angiogenesis effects, which were rescued by KRAS expression. We established a nude mouse xenograft model to investigate the specific role of miR-19a in solid tumors. The results revealed that the sizes of xenograft tumors and density of blood vessels developed from HCT116 cells expressing miR-19a were smaller/lower compared with those of the control. KRAS and VEGFA levels were also reduced. In conclusion, our results revealed that miR-19a overexpression supressed KRAS expression and angiogenesis in CRC, indicating possibilities of using miR-19a in future therapeutic applications.

PTHrP treatment of colon cancer cells promotes tumor associated-angiogenesis by the effect of VEGF

“…In other hand, it has been reported that the mutations of APC gene is very frequent in several CRC cell lines as Caco-2 (APC mutant), however, this mutation is not present in HCT116 cell line (APC WT) (Ilyas et al, 1997). Although mutations of KRAS, PIK3CA and APC correlate with VEGF expression and angiogenesis (Yeh et al, 2017;Chen et al, 2018;Lai et al, 2015;…”

LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1

“…In contrast, miR-19a-3p expression is reduced in osteosarcoma, and silencing miR-19a-3p suppresses osteosarcoma cell proliferation and induces apoptosis [32]. In addition, miR-19a-3p is reported to be down-regulated and to further inhibit the angiogenesis of CRC cells [33]. However, how miR-19a-3p was controlled in CRC remained unclear.…”

LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1

“…In contrast, miR-19a-3p expression is reduced in osteosarcoma, and silencing miR-19a-3p suppresses osteosarcoma cell proliferation and induces apoptosis [32]. In addition, miR-19a-3p was reported to be downregulated and further inhibited the angiogenesis of CRC cells [33]. However, how miR-19a-3p was controlled in CRC remained unclear.…”