The potential use and experimental validation of genomic instability-related lncRNA in pancreatic carcinoma.

This study explored the potential role of long noncoding RNA (lncRNAs) associated with genomic instability in the diagnosis and treatment of pancreatic adenocarcinoma (PAAD). Transcriptome and single-nucleotide variation data of PAAD samples were downloaded from the cancer genome atlas database to explore genomic instability-associated lncRNAs. We constructed a genomic instability-associated lncRNA prognostic signature. Then gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were used to explore the physiological role of lncRNAs involved in genomic instability. Tumor microenvironments, immunotherapy response, immune cell infiltration, immune checkpoint, and drug sensitivity were compared between high-risk and low-risk groups. In vitro experiments were performed for external validation. Six lncRNAs associated with genomic instability were identified, capable of predicting the prognosis of PAAD. Patients were assigned to low-risk or high-risk groups using these biomarkers, with better or worse prognosis, respectively. The tumor immune score, immune cell infiltration, and efficacy of immunotherapy were worse in the high-risk group. A drug sensitivity analysis revealed the high- and low-risk groups had different half-maximal inhibitory concentrations. The expression of cancer susceptibility candidate 8 was significantly higher in tumor tissues than in normal tissues, while the expression of LYPLAL1-AS1 exhibited an opposite pattern. They may be potential diagnostic or prognostic biomarkers for patients with pancreatic cancer. Genomic instability-associated lncRNAs were explored in this study and predicted the prognosis of PAAD and stratified patients risk in PAAD. These lncRNAs also predicted the efficacy of immunotherapy and potential therapeutic targets in PAAD.

CCT6A promotes esophageal squamous cell carcinoma cell proliferation, invasion and epithelial-mesenchymal transition by activating TGF-ß/Smad/c-Myc pathway.

OBJECTIVE: Chaperonin-containing TCP1 subunit 6A (CCT6A) facilitates several malignant cancer behaviors, but its regulation of esophageal squamous cell carcinoma (ESCC) has not been reported. This study aimed to investigate the effect of CCT6A on cell proliferation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) and its interaction with the TGF-ß/Smad/c-Myc pathway in ESCC. METHODS: CCT6A expression was detected in ESCC and normal esophageal epithelial cell lines by RT‒qPCR and western blotting. Furthermore, CCT6A siRNA, negative control (NC) siRNA, CCT6A encoding plasmid and NC encoding plasmid were transfected into OE21 and TE-1 cells. Subsequently, CCT6A siRNA- and NC siRNA-transfected cells were treated with TGF-ß for rescue experiments. Cell proliferation, apoptosis, invasion, and E-cadherin/N-cadherin and p-Smad2/p-Smad3/c-Myc expression were detected. RESULTS: CCT6A expression was increased in KYSE-180, TE-1, TE-4 and OE21 cells compared with HET-1A cells. In both OE21 and TE-1 cells, CCT6A knockdown inhibited cell proliferation, invasion and N-cadherin expression while promoting cell apoptosis and E-cadherin expression; meanwhile, CCT6A overexpression had the opposite effects. Furthermore, in both OE21 and TE-1 cells, CCT6A knockdown decreased p-Smad2/Smad2, p-Smad3/Smad3 and c-Myc/GAPDH expression; CCT6A overexpression had the opposite effects. Next, TGF-ß facilitated cell proliferation, invasion, and N-cadherin, p-Smad2/Smad2, p-Smad3/Smad2 and c-Myc/GAPDH expression while repressing cell apoptosis and E-cadherin expression in OE21 and TE-1 cells; importantly, TGF-ß could compensate for the regulation of CCT6A knockdown on these activities. CONCLUSION: CCT6A facilitates ESCC malignant activities by activating the TGF-ß/Smad/c-Myc pathway, which sheds light on the identification of a possible therapeutic target in the management of ESCC.

Ab initio prediction of the electronic, magnetic and topological properties of Ln2O3 clusters.

The structural, electronic and magnetic properties of the lanthanide oxide Ln2O3 clusters, where Ln signifies lanthanides from La to Lu, have been calculated using spin-polarized density functional theory with the B3LYP hybrid functional. The intensities of ferromagnetic RKKY interaction are found comparable with that of antiferromagnetic superexchange interaction in Ce2O3 / Pr2O3 / Nd2O3 / Gd2O3 / Tb2O3 / Tm2O3 clusters, while the other Ln2O3 clusters prefer ferromagnetic states to antiferromagnetic states in energy, except nonmagnetic La2O3 and Lu2O3 clusters. The theoretical spin magnetic moments, calculated three-dimensional spin density maps and dipole moments of Ln2O3 clusters suggest that the induced polarizations of oxygen atoms in Sm2O3, Eu2O3 and Yb2O3 clusters remarkably lead to the elongated Ln-O bond lengths in these clusters. The partial density of states of Ln2O3 clusters reveals that Sm3+ /Eu3+ /Yb3+ ions are distinctive from other Ln3+ ions in that their Ln-4f electrons are strongly hybrid with O-2 p electrons. The topological analysis of the electron density was also performed with quantum theory of atoms in molecules, which indicates the ionic Ln-O bonds have partial covalent characteristics.