Integration of scRNA and bulk RNA-sequence to construct the 5-gene molecular prognostic model based on the heterogeneity of thyroid carcinoma endothelial cell.

Thyroid cancer (TC) is a kind of cancer with high heterogeneity, which leads to significant difference in prognosis. The prognostic molecular processes are not well understood. Cancer cells and tumor microenvironment (TME) cells jointly determine the heterogeneity. However, quite a little attention was paid to cells in the TME in the past years. In this study, we not only reveal that endothelial cells (ECs) are strongly associated with the progress of papillary thyroid cancer (PTC) using single-cell RNA-seq (scRNA-seq) data downloaded from Gene Expression Omnibus (GEO) and WGCNA, but also screen 5 crucial genes of ECs: CLDN5, ABCG2, NOTCH4, PLAT, and TMEM47. Furthermore, the 5-gene molecular prognostic model is constructed, which can predict how well a patient will do on PD-L1 blockade immunotherapy for TC and evaluate prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrates that PLAT is decreased in TC and the increase of PLAT can restrain the migratory capacity of TC cells. Meanwhile, in TC cells, PLAT suppresses VEGFa/VEGFR2-mediated human umbilical vascular endothelial cell (HUVEC) proliferation and tube formation. Totally, we construct the 5-gene molecular prognostic model from the perspective of EC and provide a new idea for immunotherapy of TC.

Proteomics Analysis of Polyphyllin D-Treated Triple-Negative Breast Cancer Cells Reveal the Anticancer Mechanisms of Polyphyllin D.

Polyphyllin D (PD), one of the important steroid saponins in traditional medicinal herb Paris polyphylla, has been demonstrated to have anticancer activity both in vitro and in vivo. However, the mechanisms through which PD exerts its anticancer effects in triple-negative breast cancer (TNBC) remain unclear. Our study was presented to evaluate the anticancer effect and the potential mechanisms of PD in two TNBC cell lines, BT-549 and MDA-MB-231. Through comprehensively comparing the liquid chromatography-tandem mass spectrometry (LC-MS/MS) data of PD-treated and untreated BT-549 and MDA-MB-231 cells, we found that PD could induce apoptosis of TNBC cells by activating oxidative phosphorylation pathway in BT-549 cells, as well as inhibiting spliceosome function alteration in MDA-MB-231 cells. These results suggested that the mechanisms underlying the pro-apoptotic effect of PD on TNBC may be cell type-specificity-dependent. Moreover, we found that nodal modulator 2/3 (NOMO2/3) were downregulated both in PD-treated BT-549 and MDA-MB-231 cells, suggesting that NOMO2/3 may be the potential target of PD. Verification experiments revealed that PD deceased NOMO2/3 expression at protein level, rather than mRNA level. Whether NOMO2/3 are the upstream modulators of oxidative phosphorylation pathway and spliceosome needs further validation. In conclusion, a comprehensive proteomics study was performed on PD-treated or untreated TNBC cells, revealing the anticancer mechanisms of PD.

[Construction and performance analysis of a microbial electrochemical sensor for monitoring heavy metals in water environment].

A microbial fuel cell (MFC)-based microbial electrochemical sensor was developed for real-time on-line monitoring of heavy metals in water environment. The microbial electrochemical sensor was constructed with staggered flow distribution method to optimize the parameters such as external resistance value and external circulation rate. The inhibition of concentration of simulated heavy metal wastewater on voltage under optimal parameters was analyzed. The results showed that the best performance of MFC electrochemical sensor was achieved when the external resistance value was 130 Ω and the external circulation rate was 1.0 mL/min. In this case, the microbial electrochemical sensors were responsive to 1-10 mg/L Cu2+, 0.25-1.25 mg/L Cd2+, 0.25-1.25 mg/L Cr6+ and 0.25-1.00 mg/L Hg2+ within 60 minutes. The maximum rejection rates of the output voltage were 92.95%, 73.11%, 82.76% and 75.80%, respectively, and the linear correlation coefficients were all greater than 0.95. In addition, the microbial electrochemical sensor showed a good biological reproducibility. The good performance for detecting heavy metals by the newly developed microbial electrochemical sensor may facilitate the real-time on-line monitoring of heavy metals in water environment.

Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1.

Proteins in the tripartite motif-containing protein (TRIM) family participates in carcinogenesis. However, little attention was focused on the role of TRIM6 on development of breast cancer. Expression level of TRIM6 was found to be markedly enhanced in breast cancer cells and tissues. Functional assays demonstrated that overexpression of TRIM6 promoted breast cancer progression through increase of YAP1 (Yes-associated Protein 1), while knockdown of TRIM6 suppressed in vitro breast cancer progression and in vivo tumor growth through decrease of YAP1. Co-Immunoprecipitation (co-IP) showed that TRIM6 interacted with STUB1 (stress induced phosphoprotein 1 homology and U-box containing protein 1). TRIM6 promoted ubiquitination-mediated degradation of STUB1 to promote YAP1 signaling. Overexpression of STUB1 attenuated TRIM6-induced promotion of breast cancer growth. In conclusion, TRIM6 contributed to breast cancer progression through ubiquitination-dependent proteasomal degradation of STUB1 and provocation of YAP1 pathway, providing potential therapeutic target for breast cancer.

circFAT1(e2) Promotes Papillary Thyroid Cancer Proliferation, Migration, and Invasion via the miRNA-873/ZEB1 Axis.

Circular RNAs (circRNAs) play an extremely important regulatory role in the occurrence and development of various malignant tumors including papillary thyroid cancer (PTC). circFAT1(e2) is a new type of circRNA derived from exon 2 of the FAT1 gene, which is distributed in the cytoplasm and nucleus of PTC cells. However, so far, the role of circFAT1(e2) in PTC is still unclear. In this study, circFAT1(e2) was found to be highly expressed in PTC cell lines and tissues. circFAT1(e2) knockdown suppressed PTC cell growth, migration, and invasion. Also, circFAT1(e2) acted as a sponge for potential microRNAs (miRNAs) to modulate cancer progression. A potential miRNA target was discovered to be miR-873 which was targeted by circFAT1(e2) in PTC. The dual-luciferase assay conducted later also confirmed that there was indeed a direct interaction between circFAT1(e2) and miR-873. This study also confirmed that circFAT1(e2) inhibited the miR-873 expression and thus promoted the ZEB1 expression, thus affecting the proliferation, metastasis, and invasion of PTC cells. In conclusion, the results of this study indicated that circFAT1(e2) played a carcinogenic role by targeting the miR-873/ZEB1 axis to promote PTC invasion and metastasis, which might become a potential novel target for therapy of PTC.