Decreased miR-200a-3p is a key regulator of renal carcinoma growth and migration by directly targeting CBL.

Although emerging evidence has revealed that microRNAs (miRNAs) dysregulation contribute to carcinogenesis, the mechanism underlying their roles in renal cell carcinoma (RCC) is unclear. The purpose of the current study was to analyze the association of miR-200a-3p expression with RCC and to understand potential novel target genes, functions and mechanisms of miR-200a-3p in RCC. MiR-200a-3p expression levels were first measured by quantitative real-time polymerase chain reaction and in situ hybridization in pairs of RCC tissue samples. Next, the potential miR-200a-3p target gene was analyzed using a combination of computer-aided algorithms, luciferase reporter assays and Western blot analysis. Finally, the biological roles of miR-200a-3p in RCC tumorigenesis were investigated both in vitro by 5-ethynyl-20-deoxyuridine, apoptosis assay and transwell assay, as well as in vivo using a xenograft mouse model. Our results demonstrated that miR-200a-3p was remarkably downregulated in RCC tissues compared with normal adjacent tissue, and CBL is a direct target of miR-200a-3p. An inverse correlation between miR-200a-3p and CBL was observed in RCC tissue samples. Mechanistic investigations revealed that ectopic expression of miR-200a-3p in RCC cell lines suppressed cell proliferation and migration and enforced cell apoptosis by directly inhibiting CBL in vitro and in vivo, whereas silencing miR-200a-3p resulted in the opposite effects. Additionally, overexpressing CBL abolished the effects induced by miR-200a-3p overexpression. Taken together, our results show that the miR-200a-3p/CBL regulation axis is a novel mechanism underlying RCC pathogenesis and may serve as a candidate biomarker and therapeutic target in RCC.

Fibrinogen-to-albumin ratios are related to mortality in patients with secondary malignant neoplasm of bone and bone marrow.

Background: Systemic inflammation has long been considered to be one of the mechanisms in the development and progression of secondary malignant neoplasm of bone and bone marrow (BM). Fibrinogen-to-albumin ratio (FAR) has been demonstrated to be vital to the poor prognosis of lots of disease such as tumor and coronary heart disease. This study aimed to determine whether FAR could be used as an independent risk prognostic factor in patients with BM. Methods: Firstly, the baseline data of patients with BM, who met our inclusion/exclusion criteria, were extracted and analyzed from MIMIC-III database. The association between FAR and endpoints was analyzed using a Cox proportional hazards regression model and a propensity score matched analysis. Results: The univariate analysis revealed that for the 30-day mortality, the HR (95% CI) in the FAR ≥99.5group was 1.47 (1.15,1.91). After adjusting various factors, FAR ≥99.5 was found to be an independent significant risk factor for death in patients with BM (HR = 1.11, 95% CI: 1.01-1.42). Similarly, for the one-year mortality, HR (95% CI) in the FAR ≥99.5 group was 1.51 (1.11, 2.06). Conclusion: It has been found that FAR provides independent prognostic information for mortality among patients with secondary malignant neoplasms of the bone and bone marrow.

miR-28-5p acts as a tumor suppressor in renal cell carcinoma for multiple antitumor effects by targeting RAP1B.

The incidence and mortality rate of renal cell carcinoma (RCC) have been significantly increasing; however, the mechanisms involved in RCC development and progression are unclear. In this study, we found that miR-28-5p was decreased in RCC tumor specimens and several renal carcinoma cell lines. By using a combination of luciferase reporter assays and western blotting, we identified RAP1B, a Ras-related small GTP-binding oncoprotein implicated in a variety of tumors, as a direct target of miR-28-5p in RCC. The RAP1B protein level was increased in RCC tumor specimens and renal carcinoma cell lines, and this was inversely correlated with miR-28-5p expression. In vitro gain-of-function and loss-of-function studies in human renal carcinoma cell lines, demonstrated that miR-28-5p suppressed cell proliferation and migration by directly inhibiting RAP1B, and this effect was reversed by co-transfection with RAP1B. In addition, the stable overexpression of miR-28-5p inhibited tumor cell proliferation in vivo. This newly identified miR-28-5p/RAP1B axis provides a novel mechanism for the pathogenesis of RCC, and molecules in this axis may serve as potential biomarkers and therapeutic targets for RCC.