Sunitinib abrogates RCC cell invasion and metastasis via depressing miR-452-5p.
a Presented are heatmap of the most differentially expressed miRNAs in peripheral blood under Sunitinib treatment (
GSE32099) and between tumor tissue and pair-matched normal tissues(
GSE37989).
b The above analysis showed 10 miRNAs were significantly differentially expressed both in
GSE32099 and
GSE37989.
c qRT-PCR assays for miR-452-5p expression with 0, 5 and 10 μM Sunitinib treatment in OSRC-2 and SW839 cells.
d-
e Representative micrographs of wound-healing assay and decrease in wound width was induced by transfection of miR-452-5p in OSRC-2 and SW839 cells versus miR-NC cells with treatment of 10 μM Sunitinib.
f-
g Representative images and number of invasive cells per high-power field was induced by transfection of miR-452-5p in OSRC-2 and SW839 cells versus miR-NC cells with treatment of 10 μM Sunitinib.
h Orthotopic xenograft animal models were generated using miR-452-5p or miR-NC in OSRC-2 cells and mice treated with 10 μM Sunitinib. Presented are representative images (left) of abdominal metastasis viewed by IVIS system in each group 4 weeks after the orthotopic xenograft transplantation (
n=8) and Quantitation of metastasis nodules shown at right.
i Incidence of metastasis in orthotopic xenografts after 4 weeks.
j TCGA cohort analysis of the differentially expressed levels of miR-452-5p in RCC tumor samples and pair-matched normal tissues. Each dot represents one sample.
k Comparison of miR-452-5p expression in 20 paired RCC tumor tissues and adjacent normal tissues via qRT-PCR.
l Relative miR-452-5p expression levels in RCC samples are presented as fold change=2(∆Ct normal-∆Ct tumor) of tumor versus matched normal tissues, 85% of which was upregulated in tumor tissues than adjacent normal tissues.
m miR-452-5p expression in a series of RCC cell lines (SW839, A498, SN12-PM6 and OSRC-2) and human normal renal tubular epithelial cell line HK-2.
n ROC analysis to assess the specificity and sensitivity of miR-452-5p to differentiate between RCC and normal tissues.
o Kaplan–Meier analyses of the correlations between miR-452-5p expression level and overall survival of 806 patients with RCC through TCGA analysis. The median expression level was used as the cutoff. Data shown are mean±S.D. *
p<0.05, **
p<0.01