Ubiquitin-conjugating enzyme E2C (UBE2C) has been previously reported to correlate with the malignant progression of various human cancers, however, the exact molecular function of UBE2C in breast carcinoma (BRCA) remained elusive. We aimed to investigate UBE2C expression in BRCA and its clinical significance. The expression of UBE2C in 209 BRCA tissue samples and 53 adjacent normal tissue samples was detected using immunohistochemistry. The clinical role of UBE2C was analyzed. Public databases including the human protein atlas and Oncomine were used to assess UBE2C expression in BRCA. Moreover, the cancer genome atlas (TCGA) database was employed to investigate the prognostic value of UBE2C in BRCA. The positive expression rate of UBE2C in BRCA was 70.8% (148/209), and UBE2C expression in the adjacent breast tissue was negative. The expression of UBE2C was positively correlated with tumor size (r = 0.32, P < 0.001), histological grade (r = 0.237, P = 0.001), clinical stage (r = 0.198, P = 0.004), lymph node metastasis (r = 0.155, P = 0.026), HER2 expression level (r = 0.356, P < 0.001), Ki-67 expression level (r = 0.504, P < 0.001), and P53 expression level (r = 0.32, P = 0.001). Negative correlations were found between UBE2C expression and the ER (r = − 0.403, P < 0.001) and PR (r = − 0.468, P < 0.001) status. UBE2C gene expression data from the public databases all proved that UBE2C was overexpressed in BRCA. According to the TCGA data analysis, a higher positive expression of UBE2C was associated with worse survival of BRCA patients (P = 0.0428), and data from cBioPortal indicated that 11% of all sequenced BRCA patients possessed a gene alteration of UBE2C, predominately gene amplification and mRNA regulation. Ubiquitin-conjugating enzyme E2C might pose an oncogenic effect on the progression of BRCA.

Background: MiR-182-5p, a cancer-related microRNA (miRNA), modulates tumorigenesis and patient outcomes in various human malignances. This study interroted the clinicopathological significance and molecular mechanisms of miR-182-5p in non-small cell lung cancer (NSCLC). Methods: The clinical significance of miR-182-5p in NSCLC subtypes was determined based on an analysis of 124 samples (lung adenocarcinomas [LUADs], n = 101; lung squamous cell carcinomas [LUSCs], n = 23) obtained from NSCLC patients and paired noncancer tissues and an analysis of data obtained from public miRNA-seq database, miRNA-chip database, and the scientific literature. The NSCLC samples (n = 124) were analyzed using the real-time quantitative polymerase chain reaction (RT-qPCR). Potential targets of miR-182-5p were identified using lists generated by miRWalk v.2.0, a comprehensive atlas of predicted and validated targets of miRNA-target interactions. Molecular events of miR-182-5p in NSCLC were unveiled based on a functional analysis of candidate targets. The association of miR-182-5p with one of the candidate target genes, homeobox A9 (HOXA9), was validated using in-house RT-qPCR and dual-luciferase reporter assays. Results: The results of the in-house RT-qPCR assays analysis of data obtained from public miRNA-seq databases, miRNA-chip databases, and the scientific literature all supported upregulation of the expression level of miR-182-5p level in NSCLC. Moreover, the in-house RT-qPCR data supported the influence of upregulated miR-182-5p on malignant progression of NSCLC. In total, 774 prospective targets of miR-182-5p were identified. These targets were mainly clustered in pathways associated with biological processes, such as axonogenesis, axonal development, and Ras protein signal transduction, as well as pathways involved in axonal guidance, melanogenesis, and longevity regulation, in multiple species. Correlation analysis of the in-house RT-qPCR data and dual-luciferase reporter assays confirmed that HOXA9 was a direct target of miR-182-5p in NSCLC. Conclusions: The miR-182-5p expression level was upregulated in NSCLC tissues. MiR-182-5p may exert oncogenic influence on NSCLC through regulating target genes such as HOXA9.

To examine the clinical value of miR-198-5p in lung squamous cell carcinoma (LUSC). Gene Expression Omnibus (GEO) microarray datasets were used to explore the miR-198-5p expression and its diagnostic value in LUSC. Real-time reverse transcription quantitative polymerase chain reaction was used to evaluate the expression of miR-198-5p in 23 formalin-fixed, paraffin-embedded (FFPE) LUSC tissues and corresponding non-cancerous tissues. The correlation between miR-198-5p expression and clinic pathological features was assessed. Meanwhile, putative target messenger RNAs of miR-198-5p were identified based on the analysis of differentially expressed genes in the Cancer Genome Atlas (TCGA) and 12 miRNA prediction tools. Subsequently, the putative target genes were sent to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. MiR-198-5p was low expressed in LUSC tissues. The combined standard mean difference (SMD) values of miR-198-5p expression based on GEO datasets were − 0.30 (95% confidence interval (CI) − 0.54, − 0.06) and − 0.39 (95% CI − 0.83, 0.05) using fixed effect model and random effect model, respectively. The sensitivity and specificity were not sufficiently high, as the area under the curve (AUC) was 0.7749 (Q* = 0.7143) based on summarized receiver operating characteristic (SROC) curves constructed using GEO datasets. Based on the in-house RT-qPCR, miR-198-5p expression was 4.3826 ± 1.7660 in LUSC tissues and 4.4522 ± 1.8263 in adjacent normal tissues (P = 0.885). The expression of miR-198-5p was significantly higher in patients with early TNM stages (I-II) than that in cases with advanced TNM stages (III-IV) (5.4400 ± 1.5277 vs 3.5690 ± 1.5228, P = 0.008). Continuous variable-based meta-analysis of GEO and PCR data displayed the SMD values of − 0.26 (95% CI − 0.48, − 0.04) and − 0.34 (95% CI − 0.71, 0.04) based on fixed and random effect models, respectively. As for the diagnostic value of miR-198-5p, the AUC based on the SROC curve using GEO and PCR data was 0.7351 (Q* = 0.6812). In total, 542 genes were identified as the targets of miR-198-5p. The most enriched Gene Ontology terms were epidermis development among biological processes, cell junction among cellular components, and protein dimerization activity among molecule functions. The pathway of non-small cell lung cancer was the most significant pathway identified using Kyoto Encyclopedia of Genes and Genomes analysis. The expression of miR-198-5p is related to the TNM stage. Thus, miR-198-5p might play an important role via its target genes in LUSC.

Studies have shown that miR-146a-5p was differentially expressed in diverse cancers, but the associations between miR-146a-5p expression and prognosis across multiple types of cancer as well its potential targets and downstream pathways have not been comprehensively analyzed. In this study, we performed the first meta-analysis of the prognostic value of miR-146a-5p expression in diverse malignancies and explored prospective targets of miR-146a-5p and related signaling pathways. A thorough search for articles related to miR-146a-5p was performed, and RNA-seq data from The Cancer Genome Atlas (TCGA) and microarray data from gene expression omnibus profiles were used to collect information about the prognostic value of miR-146a-5p. A comprehensive meta-analysis was conducted. Twelve platforms in miRWalk 2.0 were applied to predict targets of miR-146a-5p. TCGA RNA-seq data were used to validate the inverse relationships between miR-146a-5p and its likely targets. Subsequently, gene ontology and pathway analyses were conducted using Funrich version 3.1.3. Potential protein–protein interaction (PPI) networks were constructed. Potential target genes of miR-146a-5p in lung cancer were validated by RT-qPCR. We included 10 articles in the meta-analysis. In a pooled analysis, the high miR-146a-5p expression group showed a better overall survival in solid cancers, particularly in reproductive system cancers and digestive system cancers. A total of 120 predicted target genes were included in a bioinformatics analysis. Five pathways involving phospholipase C (PLC) and aquaporins (AQPs) were the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways. Moreover, the PPI network displayed the related signaling pathways and interactions among proteins. AQP1 and FYN were validated by RT-qPCR to be potential targets of miR-146a-5p in lung cancer. There is a close link between high miR-146a-5p expression and better overall survival in 21 types of solid cancer, especially in reproductive system and digestive system cancers. Furthermore, miR-146a-5p could inhibit diverse malignancies by modulating pathways linked to PLC or AQPs. In summary, miR-146a-5p is a potential prognostic biomarker and therapeutic target for various cancers.

Introduction. We aimed to explore the downregulation of the coiled-coil domain containing 80 (CCDC80) and its underlying molecular mechanisms in ovarian carcinoma (OVCA). Materials/Methods. Immunohistochemical staining was performed to confirm the expression status of CCDC80 protein. Combining the data from in-house tissue microarrays and high-throughput datasets, we identified the expression level of CCDC80 in OVCA. We utilized cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm and single-sample gene set enrichment analysis (ssGSEA) to explore the relationship between CCDC80 and the tumor microenvironment (TME) landscape in OVCA. Pathway enrichment, function annotation, and transcription factor (TFs) exploration were conducted to study the latent molecular mechanisms. Moreover, the cell line data in the Genomics of Drug Sensitivity in Cancer (GDSC) database was used to discover the relationship between CCDC80 and drug sensitivity. Results. An integrated standard mean difference (SMD) of −0.919 (95% CI: −1.515–0.324, ) identified the downregulation of CCDC80 in OVCA based on 1048 samples, and the sROC ( ) showed a moderate discriminatory ability of CCDC80 in OVCA. The fraction of infiltrating naive B cells showed significant differences between the high- and low-CCDC80 expression groups. Also, CCDC80-related genes are enriched in the Ras signaling pathway and metabolic of lipid. Nuclear receptor subfamily three group C member 1 (NR3C1) may be an upstream TF of CCDC80, and CCDC80 may be related to the sensitivity of mitocycin C and nilotinib. Conclusion. CCDC80 was downregulated in OVCA and may play a role as a tumor suppressor in OVCA.

Liang SW, et al. Ann Surg Treat Res. 2020 Aug;99(2):118-126. https://doi.org/10.4174/astr.2020.99.2.118