RESUMEN
Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results:BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA-miRNA-mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Biología Computacional , Femenino , Estudios de Seguimiento , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , MicroARNs/genética , Persona de Mediana Edad , Pronóstico , Mapas de Interacción de Proteínas , ARN Largo no Codificante/genética , ARN Mensajero/genética , Tasa de Supervivencia , Transcriptoma , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismoRESUMEN
Colorectal cancer (CRC) is one of the most frequent cancers occurring in developed countries. Distant CRC metastasis causes more than 90% of CRC-associated mortality. MicroRNAs (miRNAs) play a key role in regulating tumor metastasis and could be potential diagnostic biomarkers in CRC patients. This study is aimed at identifying miRNAs that can be used as diagnostic biomarkers for CRC metastasis. Towards this goal, we compared the expression of five miRNAs commonly associated with metastasis (i.e., miR-10b, miR-200c, miR-155, miR-21, and miR-31) between primary CRC (pCRC) tissues and corresponding metastatic lymph nodes (mCRC). Further, bioinformatics analysis of miR-31 was performed to predict target genes and related signaling pathways. Results showed that miR-31, miR-21, miR-10b, and miR-155 expression was increased to different extents, while miR-200c expression was lower in mCRC than that in pCRC. Moreover, we found that the level of both miR-31 and miR-21 was notably increased in pCRC when lymph node metastasis (LNM) was present, and the increase of miR-31 expression was more profound. Hence, upregulated miR-31 and miR-21 expression might be a miRNA signature in CRC metastasis. Moreover, we detected a higher miR-31 level in the plasma of CRC patients with LNM compared to patients without LNM or healthy individuals. With the bioinformatics analysis of miR-31, 121 putative target genes and transition of mitotic cell cycle and Wnt signaling pathway were identified to possibly play a role in CRC progression. We next identified seven hub genes via module analysis; of these, TNS1 was most likely to be the target of miR-31 and had significant prognostic value for CRC patients. In conclusion, miR-31 is significantly increased in the cancer tissues and plasma of CRC patients with LNM; thus, a high level of miR-31 in the plasma is a potential biomarker for the diagnosis of LNM of CRC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Metástasis Linfática/diagnóstico , MicroARNs/sangre , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Biología Computacional , Regulación Neoplásica de la Expresión Génica/genética , Ontología de Genes , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática/genética , Metástasis Linfática/patología , MicroARNs/genética , MicroARNs/metabolismo , Familia de Multigenes , Estadificación de Neoplasias , Pronóstico , Mapas de Interacción de Proteínas , Regulación hacia Arriba , Vía de Señalización Wnt/genéticaRESUMEN
BACKGROUND: Noncoding RNAs are crucial regulators acting as either tumor suppressor genes or oncogenes in human cancer progression. The aberrant expression of noncoding RNAs has been confirmed in different kinds of cancers. Hepatocellular carcinoma is one of the most common malignant tumors worldwide, characterized by insidious onset, great malignancy, and high rates of recurrence and metastasis. Due to lack of early predictive markers, numerous patients are diagnosed in the late stages. As therapeutic options for advanced patients are quite limited, great efforts have been made to screen patients at early stages. A previous study reported that small nucleolar RNA host gene 18 played crucial role in glioma. However, its functions and roles in hepatocellular carcinoma are unknown. PURPOSE: To explore its functional role and diagnostic value in hepatocellular carcinoma, we investigated its expression level. METHODS: We performed real-time quantitative polymerase chain reaction in tumor tissues and adjacent noncancerous tissues derived from patients with hepatocellular carcinoma as well as in plasma, including samples from the healthy control, patients with hepatitis B, cirrhosis, and hepatocellular carcinoma. RESULTS: Small nucleolar RNA host gene 18 was downregulated in liver tissues compared to paired adjacent noncancerous tissues ( P < .0001). Meanwhile, plasma small nucleolar RNA host gene 18 showed a relatively high sensitivity and specificity (75.61% and 73.49%) for distinguishing patients with hepatocellular carcinoma whose α-fetoprotein levels were below 200 ng/mL from the healthy controls. CONCLUSION: Our study suggested that small nucleolar RNA host gene 18 might act as a tumor suppressor gene in hepatocellular carcinoma and potentially a diagnostic indicator to distinguish hepatocellular carcinoma from the healthy control and cirrhosis.
