Dicer suppresses MMP-2-mediated invasion and VEGFA-induced angiogenesis and serves as a promising prognostic biomarker in human clear cell renal cell carcinoma

Abstract

Dicer, a key component of the microRNA processing machinery, has been reported to exert discrepant prognostic values and biological roles in different types of cancers. Here, we investigated the function and prognostic value of Dicer in clear cell renal cell carcinoma (ccRCC). Using the retrospective ccRCC patients’ cohorts with tissue microarray (TMA), we demonstrated that Dicer expression was significantly down-regulated in ccRCC compared with renal non-tumor tissues, and negatively associated with pN status (P = 0.005), pM status (P = 0.009) and TNM stage (P =0.013). Multivariate Cox proportional hazards regression analyses showed that positive Dicer expression was an independent favorable factor for prognosis of ccRCC patients (hazard ratio (HR) = 0.709, P = 0.025 for 5-year overall survival; HR = 0.655, P = 0.008 for disease specific survival). Moreover, we found that Dicer decreased the abilities of cell migration, invasion and angiogenesis through suppressing MMP-2 and VEGFA expression. Tumor metastasis model in vivo showed much more metastatic nodules of lung in the Dicer knockdown group than the control group via increased MMP-2 expression. Our findings imply that Dicer inhibits ccRCC metastasis and may serve as promising prognostic biomarkers for ccRCC patients.

Knockdown of Tubulin Polymerization Promoting Protein Family Member 3 inhibits cell proliferation and invasion in human colorectal cancer

“…Angiogenesis has been shown to be frequently altered in tumor progression 16 - 18 . Then we determined the effect of conditioned media from CRC cells on HUVEC cells.…”

Chronic Dicer1 deficiency promotes atrophic and neovascular outer retinal pathologies in mice

“…The established role of DICER1 in mediating developmental and pathological angiogenesis and neovascularization is largely context-and tissue type-dependent. For example, whereas DICER1 ablation prevents developmental and postnatal angiogenesis in multiple diverse settings (23,(66)(67)(68)(69), DICER1 deficiency can promote neovascularization in stroke (70), angiosarcoma (71), and renal cell carcinoma (72,73). Furthermore, exogenous delivery of DICER1 suppresses tumor angiogenesis (72) and hypoxia-induced angiogenic responses in human endothelial cells (74).…”

CUL1 promotes breast cancer metastasis through regulating EZH2-induced the autocrine expression of the cytokines CXCL8 and IL11

“…For angiogenesis in vivo, the BALB/c nude mice were randomly divided into two groups, and 1 × 10 7 lentivirus-infected stable CUL1 knockdown and control MDA-MB-231 cells were suspended in 100 μl PBS, mixed with 200 μl matrigel and subcutaneously implanted into the flanks of nude mice. Animal experiments were performed as previously described 25,26 .…”