Background
Functions of CircMET (hsa_circ_0082002) which is a circular RNA and derived from MET gene remain understood incompletely. In the present study, Xp11.2 translocation/NONO-TFE3 fusion renal cell carcinoma (NONO-TFE3 tRCC) with up-regulated CircMET was employed to investigate its mechanism in cancer progression and post-transcriptional regulation.
Methods
FISH and real-time PCR were performed to explore the expression and localization circMET in NONO-TFE3 tRCC tissues and cells. The functions of circMET in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay. The regulatory mechanisms among circMET, CDKN2A and SMAD3 were investigated by luciferase assay, RNA immunoprecipitation, RNA pulldown and targeted RNA demethylation system.
Results
The expression of circMET was upregulated by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells, and overexpression of circMET significantly promoted the growth of NONO-TFE3 tRCC. Mechanistic studies revealed that circMET was delivered to cytosol by YTHDC1 in N6-methyladenosine (m6A)-depend manner. CircMET enhances mRNA decay of CDKN2A by direct interaction and recruitment of YTHDF2. Meanwhile, circMET competitively absorbed miR-1197 and prevented those from SMAD3 mRNA.
Conclusions
CircMET promotes the development of NONO-TFE3 tRCC, and the regulation to both CDKN2A and SMAD3 of circMET was revealed. CircMET has the potential to serve as a novel target for the molecular therapy of NONO-TFE3 tRCC as well as the other cancer with high-expressing circMET.
Background: Accelerated cardiovascular calcification often occurs in patients with cardiovascular disease who are on hemodialysis. We performed a meta-analysis to compare the effects of sevelamer hydrochloride and calcium-based phosphate binders on coronary artery calcification, C-reactive protein, alkaline phosphatase and intact parathyroid hormone in patients undergoing hemodialysis. Methods: We used the key words ‘sevelamer’ and ‘Renagel’ to retrieve studies from Medline, the Cochrane Library and conference proceedings. The trials searched were evaluated for eligibility and quality, and then the data were abstracted and analyzed. Results: We ultimately included 14 studies that enrolled a total of 3,271 patients. There was no difference in coronary artery calcium progression between the calcium and the sevelamer groups. Use of sevelamer, rather than calcium-based phosphate binders, was associated with significantly lower C-reactive protein levels (weighted mean difference (WMD) –1.42; 95% confidence interval (CI) –2.09 to –0.74), higher alkaline phosphatase levels (WMD 22.66; 95% CI 13.81–31.5) and higher intact parathyroid hormone levels (WMD 55.85; 95% CI 14.47–97.24). Conclusions: Treatment with sevelamer did not affect cardiovascular calcification, but there was a trend for lower C-reactive protein levels, higher alkaline phosphatase levels and intact parathyroid hormone levels among sevelamer-treated patients.
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