Analysis of the Role and Regulatory Mechanism of hsa-miR-504 in Cervical Cancer Based on The Cancer Genome Atlas Database.

Objective: This study investigated the expression and clinical value of hsa-miR-504 in cervical cancer and its possible mechanism of regulating the progress of cervical cancer. Methods: The expression of microRNAs (miRNAs) in cervical cancer was analyzed on The Cancer Genome Atlas (TCGA) database. The correlation between differentially expressed miRNAs and overall survival (OS) of cervical cancer patients was analyzed by Kaplan-Meier method. The target genes regulated downstream by hsa-miR-504 were predicted by miRWalk 2.0 and analyzed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) after differential screening. Univariate and multivariate Cox regressions were performed to screen the prognosis-related target genes. Results: There were 82 differentially expressed miRNAs between cervical cancer and noncancerous tissues in TCGA database (fold change >2, p < 0.05). Among them, nine miRNAs, including hsa-miR-504, were significantly correlated with OS in cervical cancer patients. Hsa-miR-504 was downregulated in cervical cancer, and low hsa-miR-504 expression was associated with poor prognosis. There were 2670 target genes of hsa-miR-504, and 240 target genes were further confirmed to be upregulated by TCGA database (fold change >2, p < 0.05). GO and KEGG showed that the upregulated target genes were mainly enriched in cell cycle, DNA replication, p53 signaling pathway, and so on. Kaplan-Meier survival analysis showed that 21 target genes were associated with OS in cervical cancer patients (p < 0.05). Univariate and multivariate Cox regression analysis showed that five genes were independent prognostic factors in cervical cancer. Conclusion: The low expression of hsa-miR-504 was closely related to the occurrence and development of cervical cancer, and hsa-miR-504 might be a potential molecular marker for favorable prognosis in cervical cancer. Cell cycle, DNA replication, and p53 signaling pathway were important mechanisms of downregulated hsa-miR-504 involved in the occurrence and development of cervical cancer.

Potential five-mRNA signature model for the prediction of prognosis in patients with papillary thyroid carcinoma.

Although the mortality rate of papillary thyroid carcinoma (PTC) is relatively low, the recurrence rates of PTC remain high. The high recurrence rates are related to the difficulties in treatment. Gene expression profiles has provided novel insights into potential therapeutic targets and molecular biomarkers of PTC. The aim of the present study was to identify mRNA signatures which may categorize PTCs into high-and low-risk subgroups and aid with the predictions for prognoses. The mRNA expression profiles of PTC and normal thyroid tissue samples were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs were identified using the 'EdgeR' software package. Gene signatures associated with the overall survival of PTC were selected, and enrichment analysis was performed to explore the biological pathways and functions of the prognostic mRNAs using the Database for Visualization, Annotation and Integration Discovery. A signature model was established to investigate a specific and robust risk stratification for PTC. A total of 1,085 differentially expressed mRNAs were identified between the PTC and normal thyroid tissue samples. Among them, 361 mRNAs were associated with overall survival (P<0.05). A 5-mRNA prognostic signature for PTC (ADRA1B, RIPPLY3, PCOLCE, TEKT1 and SALL3) was identified to classify the patients into high-and low-risk subgroups. These prognostic mRNAs were enriched in Gene Ontology terms such as 'calcium ion binding', 'enzyme inhibitor activity', 'carbohydrate binding', 'transcriptional activator activity', 'RNA polymerase II core promoter proximal region sequence-specific binding' and 'glutathione transferase activity', and Kyoto Encyclopedia of Genes and Genomes signaling pathways such as 'pertussis', 'ascorbate and aldarate metabolism', 'systemic lupus erythematosus', 'drug metabolism-cytochrome P450 and 'complement and coagulation cascades'. The 5-mRNA signature model may be useful during consultations with patients with PTC to improve the prediction of their prognosis. In addition, the prognostic signature identified in the present study may reveal novel therapeutic targets for patients with PTC.

Circulating tumor cells as a new predictive and prognostic factor in patients with small cell lung cancer.

Background: Small cell lung cancer (SCLC) is the most malignant type of lung cancer characterized by rapid progression, early metastasis and recurrence. In recent years, circulating tumor cells (CTCs) were found to play an important role in tumor invasion, metastasis, recurrence and prognosis. Methods: CTCs were detected in 138 patients with newly diagnosed SCLC from January 2012 to December 2018. Nomogram prediction models were constructed based on prognostic factors screened by multivariate Cox regression analysis and the risk stratification of SCLC patients were performed on basis of nomogram points. A total of 108 patients from January 2012 to December 2016 were assigned to a training group, and 30 patients from January 2017 to December 2018 were included into the validation group for nomogram analysis. This study was approved by ethics committee of Guangzhou First People's Hospital and all subjects provided informed consent. Results: The number of CTCs was associated with age, lymph node metastasis (N), distant metastasis (M), TNM staging, and NSE. The high number of CTC predicted adverse prognosis, and the AUC of time-dependent ROC curve was all high than 0.5. In the training group, after multivariate COX regression screening, the factors in the median survival time (MST) and overall survival (OS) nomogram prediction models were age, TNM, CTC, NSE and treatment mode. The C-index of the nomograms in internal validation for MST and OS was 0.813 and in external validation for MST and OS were 0.885. The AUC of ROC curves for nomogram were high than 0.5. Finally, risk stratification could be effectively performed on the basis of nomogram points. Conclusions: CTC can be served as a predictive and prognostic factor for SCLC, and the nomogram models constructed by CTC and multiple clinical parameters can comprehensively predict the prognosis of SCLC patients and perform risk stratification.

MicroRNA-148b enhances the radiosensitivity of B-cell lymphoma cells by targeting Bcl-w to promote apoptosis.

Lymphoma is a malignant disease of the hematopoietic system that typically affects B cells. The up-regulation of miR-148b is associated with radiosensitization in B-cell lymphoma (BCL). This study aimed to explore the role of miR-148b in regulating the radiosensitivity of BCL cells and to investigate the underlying mechanism. miR-148b directly targeted Bcl-w, decreased the cell viability and colony formation, while promoted apoptosis, in irradiated BCL cells. These changes were accompanied by decreased mitochondrial membrane potential, release of cytochrome C, increased levels of the cleaved caspase 9 and caspase 3, and increased expression of other proteins related to the mitochondrial apoptosis pathway. These effects of miR-148b were effectively inhibited by Bcl-w. In addition, miR-148b inhibited the growth of tumors in nude mice implanted with xenografts of irradiated Raji cells. In patients with BCL, levels of miR-148b were downregulated, while levels of Bcl-w were upregulated; a significant negative correlation between levels of miR-148b and Bcl-w was confirmed. Taken together, these experiments showed that miR-148b promoted radiation-induced apoptosis in BCL cells by targeting anti-apoptotic Bcl-w. miR-148b might be used as a marker to predict the radiosensitivity of BCL.