5 research outputs found
miR-216b Post-Transcriptionally Downregulates Oncogene KRAS and Inhibits Cell Proliferation and Invasion in Clear Cell Renal Cell Carcinoma
Background/Aims: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. Methods: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. Results: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3âuntranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. Conclusion: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC
Gene mutation analysis using nextâgeneration sequencing and its clinical significance in patients with myeloid neoplasm: A multiâcenter study from China
Abstract Background Myeloid neoplasms (MN) tend to relapse and deteriorate. Exploring the genomic mutation landscape of MN using nextâgeneration sequencing (NGS) is a great measure to clarify the mechanism of oncogenesis and progression of MN. Methods This multicenter retrospective study investigated 303 patients with MN using NGS from 2019 to 2021. The characteristics of the mutation landscape in the MN subgroups and the clinical value of gene variants were analyzed. Results At least one mutation was detected in 88.11% of the patients (267/303). TET2 was the most common mutation in the cohort, followed by GATA2, ASXL1, FLT3, DNMT3A, and TP53. Among patients with myeloid leukemia (ML), multivariate analysis showed that patients aged â„60âyears had lower overall survival (OS, p = 0.004). Further analysis showed TET2, NPM1, SRSF2, and IDH1 gene mutations, and epigenetic genes (pâ<â0.050) presented significantly higher frequency in older patients. In patients with myelodysplastic syndrome (MDS) and myelodysplastic neoplasms (MPN), univariate analysis showed that BCORL1 had a significant impact on OS (p = 0.040); however, in multivariate analysis, there were no factors significantly associated with OS. Differential analysis of genetic mutations showed FLT3, TP53, MUC16, SRSF2, and KDM5A mutated more frequently (pâ<â0.050) in secondary acute myeloid leukemia (sâAML) than in MDS and MPN. TP53, U2AF1, SRSF2, and KDM5A were mutated more frequently (pâ<â0.050) in sâAML than in primary AML. KDM5A was observed to be restricted to patients with sâAML in this study, and only coâoccurred with MUC16 and TP53 (2/2, 100%). Another mutation was MUC16, and its coâoccurrence pattern differed between sâAML and AML. MUC16 mutations coâoccurred with KDM5A and TP53 in 66.7% (2/3) of patients with sâAML and coâoccurred with CEBPA in 100% (4/4) of patients with AML. Conclusions Our results demonstrate different genomic mutation patterns in the MN subgroups and highlight the clinical value of genetic variants