Peifen Fu

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Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosis-related genes associated with distant metastasis and develop therapeutic strategies for COAD patients. Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA; n = 514) cohort were analyzed as a discovery dataset. Next, the data from the GEPIA database and PROGgeneV2 database were used to validate our analysis. Key genes were identified based on the differential miRNA and mRNA expression with respect to M stage. The potential drugs targeting candidate differentially expressed genes (DEGs) were also investigated. Results: A total of 127 significantly DEGs in patients with distant metastasis compared with patients without distant metastasis were identified. Then, four prognosis-related genes (LEP, DLX2, CLSTN2, and REG3A) were selected based on clustering analysis and survival analysis. Finally, three compounds targeting the candidate DEGs, including ajmaline, TTNPB, and dydrogesterone, were predicted to be potential drugs for COAD. Conclusions: This study revealed that distant metastasis in COAD is associated with a specific group of genes, and three existing drugs may suppress the distant metastasis of COAD.

Background: Growing evidence has demonstrated that glutathione peroxidases (GPXs) family genes play critical roles in onset and progression of human cancer. However, a systematic study regarding expression, diagnostic and prognostic values, and function of GPXs family genes in breast cancer remains absent. Materials and methods: Several databases were employed to perform in silico analyses for GPXs family genes. qRT-PCR, western blot and immunohistochemistry staining were introduced to validate GPX3 expression in breast cancer. The functions of GPX3 in breast cancer cells were successively determined. Results: By combination of receiver operating characteristic (ROC) curve analysis, survival analysis and expression analysis, GPX3 was considered as a potential tumor suppressor and a promising diagnostic/prognostic biomarker in breast cancer. Next, low expression of GPX3 was confirmed in breast cancer cells and tissues when compared with corresponding normal controls. Overexpression of GPX3 markedly suppressed proliferation, colony formation, migration and invasion of breast cancer in vitro. Moreover, two potential mechanisms responsible for GPX3 downregulation in breast cancer, including hypermethylation of GPX3 promoter and release of hsa-miR-324-5p inhibition. Conclusions: Collectively, we demonstrate that GPX3 is markedly downregulated in breast cancer, possesses significant diagnostic and prognostic values and attenuated in vitro growth and metastasis of breast cancer.

Pseudogenes, abundant in the human genome, are traditionally considered as non-functional “junk genes.” However, recent studies have revealed that pseudogenes act as key regulators at DNA, RNA or protein level in diverse human disorders (including cancer), among which pseudogene-derived long non-coding RNA (lncRNA) transcripts are extensively investigated and has been reported to be frequently dysregulated in various types of human cancer. Growing evidence demonstrates that pseudogene-derived lncRNAs play important roles in cancer initiation and progression by serving as competing endogenous RNAs (ceRNAs) through competitively binding to shared microRNAs (miRNAs), thus affecting both their cognate genes and unrelated genes. Herein, we retrospect those current findings about expression, functions and potential ceRNA mechanisms of pseudogene-derived lncRNAs in human cancer, which may provide us with some crucial clues in developing potential targets for cancer therapy in the future.

Ovarian cancer is one of the most common and lethal cancer types in women. The molecular mechanism of ovarian cancer progression is still unclear. Here, we first reported that expression levels of three genes, GJB2, S100A2 and SPOCK2, were significantly higher in advanced stage than that in early stage of ovarian cancer, and upregulation of them indicated poor prognosis of patients with ovarian cancer. Subsequently, 8, 6 and 20 miRNAs were predicted to target GJB2, S100A2 and SPOCK2, respectively. Among these miRNA-mRNA pairs, hsa-miR-363-3p-SPOCK2 axis was the most potential in suppressing progression of ovarian cancer. Mechanistically, we found that hsa-miR-363-3p-SPOCK2 axis was involved in regulation of actin cytoskeleton. Moreover, 6 pseudogenes and 8 lncRNAs were identified to potentially inhibit hsa-miR-363-3p-SPOCK2 axis in ovarian cancer. Collectively, we elucidate a regulatory role of pseudogene/lncRNA-hsa-miR-363-3p-SPOCK2 pathway in progression of ovarian cancer, which may provide effective therapeutic approaches and promising prognostic biomarkers for ovarian cancer. Differentially expressed genes (DEGs) in ovarian cancer were first screened using GSE12470, after which DEGs expression were validated using GEPIA. Kaplan-Meier analysis was employed to assess the prognostic values. Potential miRNAs were predicted by seven target prediction databases, and upstream lncRNAs and pseudogenes of hsa-miR-363-3p were forecasted through miRNet or starBase. UALCAN and starBase were used to obtain the co-expressed genes of SPOCK. Enrichment analysis for these co-expressed genes was performed by Enrichr.

Aim: To identify novel competing endogenous RNA (ceRNA) network related to patients prognosis in breast cancer. Materials & methods: Dysregulated mRNA based on intersection of three Gene Expression...