Mounting evidence indicates that microRNAs play important roles in the development of various cancers. Aberrant expression of microRNA-199a-5p has been frequently reported in cancer studies; however, the mechanistic details of the role of microRNA-199a-5p in colorectal cancer still remain unclear. Our study aimed to explore the role of microRNA-199a-5p in colorectal cancer cells by targeting Rho-associated coiled coil-containing protein kinase 1. Here, we showed that microRNA-199a-5p was significantly downregulated in colorectal cancer cell lines and tissue samples and was associated with a poor prognostic phenotype. MicroRNA-199a-5p suppressed colorectal cancer cell proliferation, migration, and invasion and induced cell apoptosis. Moreover, we identified Rho-associated coiled coil-containing protein kinase 1 as the direct target of microRNA-199a-5p using luciferase and Western blot assays. Importantly, Rho-associated coiled coil-containing protein kinase 1 overexpression rescued the microRNA-199a-5p-induced suppression of proliferation, migration, and invasion of colorectal cancer cells. Furthermore, the overexpression of microRNA-199a-5p inhibited tumor growth and metastasis by inactivating the phosphoinositide 3-kinase/AKT and Janus kinase 1/signal transducing activator of transcription signaling pathways through downregulation of Rho-associated coiled coil-containing protein kinase 1. Altogether, microRNA-199a-5p/Rho-associated coiled coil-containing protein kinase 1 may be a potential therapeutic target for colorectal cancer therapy.
Purpose:We aimed to determine if lactate dehydrogenase to albumin ratio (LAR) might play a prognostic role for patients with operable colorectal cancer (CRC). Patients and Methods: 1334 operable CRC patients in Wuhan Union Hospital Between July 2013 and September 2017 were enrolled in this study and were randomly appointed them into training (n=954) and validation (n=380) sets. The relationship between LAR and overall survival (OS) and disease-free survival (DFS) were determined by restricted cubic splines (RCS) with Cox regression models. LAR was then divided into three categories based on the RCS and compared to the well-known TNM stage system. Finally, survival nomograms were developed by compounding the LAR and other clinical factors. Results: Baseline LAR values and the all-cause mortality were U shaped, which slowly decreased until around 4.50 and then started to increase rapidly when the LAR ranged from 4.50-6.68 and then became flat thereafter (P for non-linearity <0.001). LAR was superior to TNM stage for OS as well as DFS and LAR plus TNM stage could add more net benefit than clinical model alone. Moreover, the survival nomograms based on LAR achieved great predictive ability for OS and DFS in operable CRC patients. Conclusions: LAR could be served as a reliable prognostic factor for OS as well as DFS, with more accurate prognostic prediction than current TNM stage for patients with operable CRC.
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