RESUMO
Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC. SNRPA was overexpressed in MVI-HCC and correlated with poor patient survival. Mechanistically, SNRPA promoted the epithelial-mesenchymal transition (EMT)-like process for HCC cells to accelerate metastasis by activating the NOTCH1/Snail pathway in vitro and in vivo. Importantly, circSEC62 upregulated SNRPA expression in HCC cells via miR-625-5p sponging. Taking these results together, our study identified a novel regulatory mechanism among SNRPA, miR-625-5p, circSEC62 and the NOTCH1/Snail pathway in HCC, which promoted metastasis of HCC and may provide effective suggestions for improving the prognosis of HCC patients with metastasis.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Metástase Neoplásica , Fatores de Processamento de RNA , RNA Circular , Humanos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Peptídeos/genética , Peptídeos/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , RNA Circular/metabolismoRESUMO
BACKGROUND: This study aims to reveal early breast cancer (BC) specific competing endogenous RNA (ceRNA) network through the expression profiles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and mRNAs. METHODS: Based on The Cancer Genome Atlas (TCGA), we obtained the differentially expressed mRNAs, miRNAs, and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) between early BC and normal samples. The lncRNA-miRNA-mRNA interaction network was constructed using Cytoscape. Functional enrichment were performed using GeneCoDis3. The expression of selected genes were validated by qRT-PCR. Based on the published dataset, we validated the result of TCGA integration analysis. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively. RESULTS: Totally, 1207 DEmRNAs, 194 DElncRNAs and 37 DEmiRNAs were obtained. Functional enrichment analysis results showed that all of DEmRNAs were enriched in pathway of cytokine-cytokine receptor interaction, PPAR signaling pathway and pathways in cancer. The DEmRNA-DEmiRNA-DElncRNA interaction network in early BC was consisted of 23 DEmiRNAs, 95 DElncRNAs and 309 DEmRNAs. Among ceRNA network, IL-6-hsa-miR-182-5p-ADAMTS9-AS1 interactions, LIFR-hsa-miR-21-5p-ADAMTS9-AS1 interactions and MMP1/MMP11-hsa-miR-145-5p-CDKN2B-AS1 interactions were speculated to involve in the development of early BC. The qRT-PCR results were consistent with our integrated analysis. Except for ADAMTS9-AS1 and CDKN2B-AS1, expression of the others results in the Gene Expression Omnibus (GEO) dataset were generally consistent with TCGA integrated analysis. The area under curve (AUC) of the ADAMTS9-AS1, CDKN2B-AS1, IL-6, MMP11, hsa-miR-145-5p and hsa-miR-182-5p were 0.947, 0.862, 0.842, 0.993, 0.960 and 0.944, and the specificity and sensitivity of the 6 biomarkers were 83.4% and 95.6%, 72.2% and 90.3%, 80.1% and 74.3%, 96.2% and 96.5%, 90.1% and 92.3%, and 88.7% and 90.4%, respectively. In addition, IL-6 had potential prognostic value for early BC. CONCLUSION: These findings may provide novel insights into the lncRNA-miRNA-mRNA network and uncover potential therapeutic targets in early BC.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , MicroRNAs/genética , RNA Mensageiro/genética , Adulto , Idoso , Neoplasias da Mama/mortalidade , Biologia Computacional/métodos , Suscetibilidade a Doenças , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Estadiamento de Neoplasias , Prognóstico , RNA Longo não Codificante/genética , Curva ROC , TranscriptomaRESUMO
Altered expression of flotillin-2 (FLOT2) has been identified in certain types of cancer, including breast cancer and melanoma; however, to the best of our knowledge, the association between the FLOT2 expression level and colorectal cancer (CRC) remains to be determined. The aim of the present study was to investigate the clinical and prognostic significance of FLOT2 in CRC. The expression of FLOT2 was determined in seven CRC cell lines and one normal colon cell line, and it was identified that FLOT2 was increased in CRC cell lines, suggesting that FLOT2 exhibited an association with CRCs. In addition, FLOT2 protein levels were investigated in primary CRC tissues and corresponding non-cancerous colon tissues from 8 patients. Compared with non-cancerous tissues, FLOT2 protein was apparently upregulated in CRC tissues. To validate this result, an immunohistochemistry assay was performed and it was identified that FLOT2 levels were increased in CRC tissues. Clinical analysis identified that increased expression of FLOT2 was associated with the depth of invasion, lymph node metastasis, distant metastasis and American Joint Committee on Cancer stage of CRCs. Furthermore, multivariate analysis using the Cox regression model indicated that increased FLOT2 expression was an independent prognostic factor in patients with CRC (P=0.013). Taken together, the results of the present study suggest that overexpression of FLOT2 contributes to the progression of CRC and indicate that FLOT2 is a novel target for the treatment of CRC.