miR-203 inhibition of renal cancer cell proliferation, migration and invasion by targeting of FGF2

Abstract

BackgroundRenal cell carcinoma (RCC) is one of the leading causes of cancer related mortality worldwide. Increasing evidence has shown that microRNAs function as oncogenes or tumor suppressors in human malignancies, but the roles of miR-203 in human RCC is still unclear.MethodsFirst, quantitative real-time PCR (qRT-PCR) was performed to detect miR-203 expression in renal cancer cell lines and clear cell RCC (ccRCC) specimens. Then, the association of miR-203 expression with clinicopathological features and survival was later analyzed. Finally, the roles of miR-203 in regulation of tumor proliferation, migration, invasion, and target gene expression were further investigated.ResultsOur study showed miR-203 was down-regulated in renal cancer cell lines and ccRCC specimens (P < 0.05). Respectively, the low miR-203 expression in ccRCC specimens was associated with advanced clinical features and poorer prognosis (P < 0.05). miR-203 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis (P < 0.05). Transient forced expression of miR-203 inhibited renal cancer cell growth and metastasis (P < 0.05). In contrast, down-regulation of miR-203 expression promoted renal cancer cell growth and metastasis (P < 0.05). Mechanistic investigations confirmed FGF2 as a direct target of miR-203, and up-regulation of miR-203 could decrease expression of FGF2. Further investigation showed that ectopic expression of FGF2 partially reversed the inhibition effect of enforced miR-203 expression on the malignant phenotypes of renal cancer cells.ConclusionsOur study suggested that miR-203 could be a potential prognostic marker and functions as a tumor suppressor in human renal cancer by post-transcriptionally targeting FGF2.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6828145701534108.

MiR-203 inhibits the proliferation, invasion, and migration of pancreatic cancer cells by down-regulating fibroblast growth factor 2

“…In this study, we found that miR-203-3p, combined with the 3' UTR region of FGF2, could exert a direct regulatory effect. These results are consistent with those of previous studies [35,36] , and they explain why miR-203 can affect the proliferation, invasion, and migration of pancreatic cancer cells. However, we also found that downregulation of miR-203 inhibited AsPC-1 cell apoptosis, but overexpression of FGF2 had no significant effect on cell viability.…”

“…For example, miR-203 is overexpressed in pancreatic cancer and not in normal pancreatic tissue and chronic pancreatitis, suggesting that miR-203 may be related to specific characteristics of tumors and their behavior [18] . Other studies have suggested that FGF2 expression may be affected by miR-203 [19,20] . However, the relevant mechanisms of action and signaling pathways in pancreatic cancer remain unknown.…”

Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas

“…It is, thus, interesting to correlate these data with the fact that miR-125b was shown to directly target FGFR-2 in a psoriasis model, suggesting another mechanism by which this miRNA could inhibit both osteoblastic differentiation and carcinogenesis ( Figure 6) [75]. In addition, miR-203 was identified as being a direct inhibitor of FGF2 in renal cancer [178]. In accordance with these results, it was also highlighted that FGFR-2 promotes osteogenic differentiation through the serine/threonine kinase protein kinase C alpha (PKCα) and the ERK1/2 pathways in murine MSCs [179].…”

Downregulation of miR-1826 Indicates a Poor Prognosis for Osteosarcoma Patients and Regulates Tumor Cell Proliferation, Migration, and Invasion

“…Aberrant expression of diverse miRNAs in tumor samples has been determined as an efficient diagnostic and prognostic biomarker in human malignancies, including OS [10]. In addition, some functional miRNAs have been indicated as potential targets in tumor targeted therapy through modulating oncogenes or tumor suppressor genes [11,12]. Thus, we believed that the investigation of miRNAs for their clinical significance and biological function could improve the prognosis and treatment of OS.…”