Pan-cancer Analysis Reveals Cancer-dependent Expression of SOX17 and Associated Clinical Outcomes.

BACKGROUND/AIM: SRY-box containing gene 17 (SOX17) plays a pivotal role in cancer onset and progression and is considered a potential target for cancer diagnosis and treatment. However, the expression pattern of SOX17 in cancer and its clinical relevance remains unknown. Here, we explored the relationship between the expression of SOX17 and drug response by examining SOX17 expression patterns across multiple cancer types. MATERIALS AND METHODS: Single-cell and bulk RNA-seq analyses were used to explore the expression profile of SOX17. Analysis results were verified with qPCR and immunohistochemistry. Survival, drug response, and co-expression analyses were performed to illustrate its correlation with clinical outcomes. RESULTS: The results revealed that abnormal expression of SOX17 is highly heterogenous across multiple cancer types, indicating that SOX17 manifests as a cancer type-dependent feature. Furthermore, the expression pattern of SOX17 is also associated with cancer prognosis in certain cancer types. Strong SOX17 expression correlates with the potency of small molecule drugs that affect PI3K/mTOR signaling. FGF18, a gene highly relevant to SOX17, is involved in the PI3K-AKT signaling pathway. Single-cell RNA-seq analysis demonstrated that SOX17 is mainly expressed in endothelial cells and barely expressed in other cells but spreads to other cell types during the development of ovarian cancer. CONCLUSION: Our study revealed the expression pattern of SOX17 in pan-cancer through bulk and single-cell RNA-seq analyses and determined that SOX17 is related to the diagnosis, staging, and prognosis of some tumors. These findings have clinical implications and may help identify mechanistic pathways amenable to pharmacological interventions.

Identification of Long Noncoding RNAs That Exert Transcriptional Regulation by Forming RNA-DNA Triplexes in Prostate Cancer.

Long noncoding RNAs (lncRNAs) are involved in transcriptional regulation, and their deregulation is associated with the development of various human cancers, including prostate cancer (PCa). However, their underlying mechanisms remain unclear. In this study, lncRNAs that interact with DNA and regulate mRNA transcription in PCa were screened and identified to promote PCa development. First, 4195 protein-coding genes (PCGs, mRNAs) were obtained from the The Cancer Genome Atlas (TCGA) database, in which 1148 lncRNAs were differentially expressed in PCa. Then, 44,270 pairs of co-expression relationships were calculated between 612 lncRNAs and 2742 mRNAs, of which 42,596 (96%) were positively correlated. Among the 612 lncRNAs, 392 had the potential to interact with the promoter region to form DNA:DNA:RNA triplexes, from which lncRNA AD000684.2(AC002128.1) was selected for further validation. AC002128.1 was highly expressed in PCa. Furthermore, AD000684.2 positively regulated the expression of the correlated genes. In addition, AD000684.2 formed RNA-DNA triplexes with the promoter region of the regulated genes. Functional assays also demonstrated that lncRNA AD000684.2 promotes cell proliferation and motility, as well as inhibits apoptosis, in PCa cell lines. The results suggest that AD000684.2 could positively regulate the transcription of target genes via triplex structures and serve as a candidate prognostic biomarker and target for new therapies in human PCa.

Dry electrochemical polishing of copper alloy in a medium containing ion-exchange resin.

Metal surfaces can be polished effectively and in an environmentally friendly way by virtue of the mechanical and electrochemical interaction between ion-exchange resin particles and the metal substrate. This paper studied this 'dry' polishing process and its property effects on 65 brass alloys. Surface morphology analysis revealed that the surface roughness can be reduced by over 71.5% from 0.764 ± 0.031 µm to 0.218 ± 0.080 µm with longer polishing time, and by over 67.1% from 0.764 ± 0.031 µm to 0.252 ± 0.02 µm with higher voltage. XPS and EDS results showed that only a small amount of oxygen species remained on the polished metal surface, while Cu and Zn were apparently present in the metallic state. The decrease in self-corrosion current indicated by the Tafel curves and the increase in the radius of the capacitive reactance circle contained in the Nyquist plots indicate that the surface corrosion resistance of the polished materials has been improved.

Transcriptional network modulated by the prognostic signature transcription factors and their long noncoding RNA partners in primary prostate cancer.

BACKGROUND: Transcriptional regulators are seminal players in the onset and progression of prostate cancer. However, clarification of their underlying regulatory circuits and mechanisms demands considerable effort. METHODS: Integrated analyses were performed on genomic, transcriptomic, and clinicopathological profiles of primary prostate cancer and transcription factor-binding profiles, which included estimating transcription factor activity, identifying transcription factors of prognostic values, and discovering cis- and trans-regulations by long noncoding RNAs. Interactions between transcription factors and long noncoding RNAs were validated by RNA immunoprecipitation quantitative PCR. RNA interference assays were performed to explore roles of the selected transcription regulators. FINDINGS: Sixteen transcription factors, namely, ETS1, ARID4B, KLF12, GMEB1, HBP1, MXI1, MYC, MAX, PGR, BCL11A, AR, KLF4, SRF, HIF1A, EHF, and ATOH1, were jointly identified as a prognostic signature. Candidate long noncoding RNAs interplaying with the prognostic signature constituent transcription factors were further discovered. Their interactions were randomly checked, and many of them were experimentally proved. Transcription regulation by MYC and its long noncoding RNA partner AL590617.2 was further validated on their candidate targets. Moreover, the regulatory network governed by the transcription factors and their interacting long noncoding RNA partners is illustrated and stored in our LNCTRN database (https://navy.shinyapps.io/lnctrn). INTERPRETATION: The prognostic signature constituent transcription factors and their interacting long noncoding RNAs may represent promising biomarkers and/or therapeutic targets for prostate cancer. Furthermore, the computational framework proposed in the present study can be utilized to explore critical transcriptional regulators in other types of cancer. FUNDING: This work was supported by National Natural Science Foundation of China and Fudan University.

Integrative analysis of AR-mediated transcriptional regulatory network reveals IRF1 as an inhibitor of prostate cancer progression.

BACKGROUND: Androgen receptor (AR) is crucial for prostate cancer (PCa) initiation and malignant progression. Only half of androgen-responsive genes have been identified as having androgen-responsive elements, suggesting that AR regulates downstream genes through other transcriptional factors. However, whether and how AR regulates the progression via regulating these androgen-responsive genes remains unclear. METHODS: Androgen-responsive and activity-changed (AC) transcriptional factors (TFs) were identified based on the time-course gene-expression array and gene promoter regions analysis. The intersection of androgen-responsive and AC TFs was selected the core TFs, which were used to construct the core transcriptional regulatory network. GO enrichment analysis, cell proliferation assays, glycolysis experiments, and reverse transcription polymerase chain reaction analysis were used to analyze and validate the functions of the network. As one of the core TFs, the function and mechanism of IRF1 have been further explored. RESULTS: We devised a new integrated approach to select core TFs and construct core transcriptional regulatory network in PCa. The 24 core TFs and core transcriptional regulatory network participate in regulating PCa cell proliferation, RNA splicing, and cancer metabolism. Further validations showed that AR signaling could promote glycolysis via inducing glycolytic enzymes in PCa cells. IRF1, a novel target of AR, served as a tumor suppressor by inhibiting PCa proliferation, cell cycle, and glycolysis. CONCLUSIONS: It is the first time to demonstrate the regulating role of the AR-mediated transcriptional regulatory network in a series of important biological processes in PCa cells. IRF1, an AR-regulated TF, acts as tumor suppressor in this core transcriptional regulatory network, which highlights the therapeutic potential of targeting this regulatory network for PCa.