RESUMEN
Background: Cysteine and Glycine Rich Protein 1 (CSRP1) belongs to the cysteine-rich protein family, which contains a unique double-zinc finger motif and is important for development and cellular differentiation. Abnormal expression of CSRP1 was reported within several malignancies such as prostate cancer and acute myeloid leukemia. Here, we explored function of CSRP1 within colon adenocarcinoma (COAD) for the first time. Methods: The mRNA levels of CSRP1 in COADs were obtained from TCGA datasets. CSRP1 protein expressions in COADs were tested via immunohistochemistry staining. Patients' prognosis was evaluated using both univariate analysis and multivariate analysis. Two human COAD originated cancer cell lines, Caco-2, and HT-29, were used for cellular experiments including shRNA knockdown, proliferation assay, and migration assay. In vivo model was established using nude mice xenografts to further validate the role of CSRP1 in COAD progression. Results: The mRNA levels of CSRP1 are elevated in COAD specimens from patients with more advanced tumor stages and higher Carcinoembryonic Antigen (CEA) levels. In addition, higher CSRP1 mRNA level indicates worse COAD prognosis. Consistently, higher CSRP1 protein expression is correlated with worse overall survival according to both univariate and multivariate analysis, indicating that CSRP1 is a new COAD prognostic factor. Furthermore, COAD cells transfected with CSRP1-shRNAs exhibit attenuated proliferation and migration capacities. Finally, growth of xenografts originated from CSRP1-knockdown cells is inhibited comparing to the control ones. Conclusions: Expression of CSRP1 is positively correlated with COAD progression, which can promote tumor growth and migration. Higher CSRP1 can is a novel independent prognostic factor of COAD.
Asunto(s)
Adenocarcinoma , Neoplasias del Colon , Animales , Humanos , Masculino , Ratones , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Biomarcadores , Células CACO-2 , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Cisteína , Ratones Desnudos , Pronóstico , ARN Mensajero/genéticaRESUMEN
BACKGROUND: The aim of this study was to explore the function and mechanism of GKN1 in gastric cancer (GC) progression. METHODS: Firstly, we used GEO2R to perform differential gene analysis on GSE26942 and GSE79973 and constructed the protein-protein interaction network of differential genes by STRING. Next, the cytoHubba, Mcode plugins, and GEPIA were used to obtain our follow-up research object GKN1. Then, the function of GKN1 in GC was verified by scratch and transwell assay in GC cells. We further analyzed the genes related to GKN1 through LinkedOmics, and exported top 100 genes positively or negatively correlated with GKN1. Meanwhile, Metascape was performed on these genes. Finally, we analyzed the miRNAs that bind to GKN1 through the miRDB and verified the correlation between miR-548d-3p and GKN1 using dual-fluorescence and quantitative PCR experiments. RESULTS: Bioinformatics analysis showed that there were 52 differential genes on GSE26942 and GSE79973. In addition, the results of functional assays indicated that overexpressed GKN1 can inhibit GC cell migration and invasion, while GKN1 knockdown demonstrated the opposite effect. Additionally, Metascape analysis results showed that the 3'-UTR region of mRNA is rich in AU sequences, based on which we infer that mRNA may be regulated by miRNA. Dual-fluorescence and quantitative PCR assays clarified that miR-548d-3p may be one of the target miRNAs of GKN1, which was up-regulated in GC tissues. CONCLUSIONS: In summary, we clarified that miR-548d-3p regulates GKN1 to participate in GC cell migration and invasion, and provides a possible target for the prognostic diagnosis and treatment of GC.
Asunto(s)
MicroARNs , Hormonas Peptídicas , Neoplasias Gástricas , Regiones no Traducidas 3' , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Hormonas Peptídicas/genética , ARN Mensajero/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMEN
In this study, high-throughput Illumina sequencing was employed to assemble the complete mitochondrial genome of the Meiren yak (Bos grunniens), a local yak breed from Gansu Province, China. The mitochondrial genome is 16,321 bp long with an A + T-biased nucleotide composition and harbors 13 protein-coding, 22 Trna, and 2 rRNA genes, and a noncoding control region. The mitogenomic organization and codon usage are highly similar to those of previously published congeneric mitochondrial genomes. Bayesian phylogenetic analysis indicates that Meiren yak is most closely related to nine other yak breeds (incl. Datong, Huanhu, Pali, Pamir, Polled, Qilian, Seron, Sunan, and Tianjun yaks).
RESUMEN
In this study, we reconstructed the complete mitochondrial genome of the hybrid of Jersey cattle (Bos taurus; â) × Gannan yak (Bos grunniens; â) from Illumina sequencing reads. The mitochondrial genome is 16,322 bp in length with an A + T-biased nucleotide composition, and encodes 13 protein-coding genes, 22 tRNAs, and 2 rRNAs along with a noncoding control region. In addition, its gene order is identical to those of previously published mitochondrial genomes of the genera Bison and Bos. Phylogenetic analysis indicates that this hybrid is most closely related to Gannan yak and Jinchuan yak.