CircVDAC3 sequesters microRNA-592 and elevates EIF4E3 expression to inhibit the progression of gastric cancer.

BACKGROUND: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. METHODS: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. RESULTS: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. CONCLUSION: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.

Ubiquitin specific peptidase 38 epigenetically regulates KLF transcription factor 5 to augment malignant progression of lung adenocarcinoma.

Protein ubiquitination is a common post-translational modification and a critical mechanism for regulating protein stability. This study aimed to explore the role and potential molecular mechanism of ubiquitin-specific peptidase 38 (USP38) in the progression of lung adenocarcinoma (LUAD). USP38 expression was significantly higher in patients with LUAD than in their counterparts, and higher USP38 expression was closely associated with a worse prognosis. USP38 silencing suppresses the proliferation of LUAD cells in vitro and impedes the tumorigenic activity of cells in xenograft mouse models in vivo. Further, we found that USP38 affected the protein stability of transcription factor Krüppel-like factors 5 (KLF5) by inhibiting its degradation. Subsequent mechanistic investigations showed that the N-terminal of USP38 (residues 1-400aa) interacted with residues 1-200aa of KLF5, thereby stabilizing the KLF5 protein by deubiquitination. Moreover, we found that PIAS1-mediated SUMOylation of USP38 was promoted, whereas SENP2-mediated de-SUMOylation of USP38 suppressed the deubiquitination effects of USP38 on KLF5. Additionally, our results demonstrated that KLF5 overexpression restored the suppression of the malignant properties of LUAD cells by USP38 knockdown. SUMOylation of USP38 enhances the deubiquitination and stability of KLF5, thereby augmenting the malignant progression of LUAD.

Nickel chloride promotes lung cancer invasion and metastasis by up-regulating the expression of E3 ubiquitin ligase TRIM31 through the IL-6/STAT3 signaling axis.

Nickel compounds are widely used in industries and daily life as important industrial products. Long-term exposure to nickel compounds has been associated with increased incidence and poor prognosis of lung cancer. However, the molecular mechanism by which exposure to nickel compounds induces the malignant phenotype of lung cancer cells remains unclear. In this study, we confirmed that nickel chloride (NiCl2) exposure promotes invasion and metastasis through IL-6/STAT3 both in vitro and vivo. Mechanistically, we found that NiCl2 mediated the transcriptional regulation of E3 ubiquitin ligase TRIM31 by SATAT3 phosphorylation, and promoted its up-regulation. Overexpression TRIM31 is an independent risk factor for lung cancer patients, and it promotes the invasion and metastasis of lung cancer cells. In addition, E3 ubiquitination ligase TRIM31 binds to its substrate TP53 protein in the RING region and accelerates TP53 protein ubiquitination and degradation. Functional recovery experiments showed that NiCl2 exposure promotes the invasion and metastasis ability of lung cancer and ubiquitination-mediated degradation of TP53 protein through the STAT3/TRIM31 axis. These findings reveal the role and mechanism of NiCl2 in lung cancer progression, indicating that STAT3 and TRIM31 may be promising targets for the treatment of lung cancer.

ZDHHC11B is decreased in lung adenocarcinoma and inhibits tumorigenesis via regulating epithelial-mesenchymal transition.

PURPOSE: The role and mechanism of zinc finger DHHC protein 11B (ZDHHC11B) in lung adenocarcinoma (LUAD) remain unclear. We, thus, analyzed the expression pattern, biological function, and potential mechanism of ZDHHC11B in LUAD. METHODS: The expression level and prognostic value of ZDHHC11B were evaluated based on The Cancer Genome Atlas (TCGA) database and further confirmed in LUAD tissues and cells. The effect of ZDHHC11B on the malignant biological progression of LUAD was evaluated in vitro and in vivo. Gene set enrichment analysis (GSEA) and western blot were used to explore the molecular mechanisms of ZDHHC11B. RESULTS: In vitro, ZDHHC11B inhibited the proliferation, migration, and invasion of LUAD cells and induced the apoptosis of LUAD cells. In addition, ZDHHC11B inhibited the growth of tumors in nude mice. GSEA revealed that ZDHHC11B expression is positively correlated with epithelial-mesenchymal transition (EMT). Western blot analysis demonstrated that molecular markers of EMT were inhibited under ZDHHC11B overexpression conditions. CONCLUSIONS: Our findings indicated that ZDHHC11B plays a significant role in inhibiting tumorigenesis via EMT. In addition, ZDHHC11B may be a candidate molecular target for LUAD treatment.

KAT7 promotes radioresistance through upregulating PI3K/AKT signaling in breast cancer.

Chromatin-modifying enzymes are commonly altered in cancers, but the molecular mechanism by which they regulate cancers remains poorly understood. Herein, we demonstrated that Lysine acetyltransferase 7 (KAT7) was upregulated in breast cancer. KAT7 expression negatively correlated with the survival of breast cancer patients, and KAT7 silencing suppressed breast cancer radioresistance in vitro. Mechanistically, KAT7 activated Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) transcription, leading to enhanced PI3K/AKT signaling and radioresistance. Overexpression of AKT or PIK3CA restored radioresistance suppression induced by KAT7 inhibition. Moreover, overexpression of KAT7, but not KAT7 acetyltransferase activity-deficient mutants promoted AKT phosphorylation at the Ser473 site, PIK3CA expression and radioresistance suppression due to KAT7 inhibition. In conclusion, KAT7 has huge prospects for clinical application as a new target for predicting radioresistance in breast cancer patients.

Methods for Measuring Thermal Conductivity of Two-Dimensional Materials: A Review.

Two-dimensional (2D) materials are widely used in microelectronic devices due to their excellent optical, electrical, and mechanical properties. The performance and reliability of microelectronic devices based 2D materials are affected by heat dissipation performance, which can be evaluated by studying the thermal conductivity of 2D materials. Currently, many theoretical and experimental methods have been developed to characterize the thermal conductivity of 2D materials. In this paper, firstly, typical theoretical methods, such as molecular dynamics, phonon Boltzmann transport equation, and atomic Green's function method, are introduced and compared. Then, experimental methods, such as suspended micro-bridge, 3ω, time-domain thermal reflectance and Raman methods, are systematically and critically reviewed. In addition, the physical factors affecting the thermal conductivity of 2D materials are discussed. At last, future prospects for both theoretical and experimental thermal conductivity characterization of 2D materials is given. This paper provides an in-depth understanding of the existing thermal conductivity measurement methods of 2D materials, which has guiding significance for the application of 2D materials in micro/nanodevices.

MYC/MAX-Activated LINC00958 Promotes Lung Adenocarcinoma by Oncogenic Transcriptional Reprogramming Through HOXA1 Activation.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. The role of the long non-coding RNA (lncRNA) LINC00958, which regulates the malignant behavior of multiple tumors, in LUAD has not been elucidated. METHODS: Tissue microarray, FISH, and qRT-PCR were used to detect the expression of LINC00958. Plasmid and viral infections were used to manipulate gene expression. The role of LINC00958 in LUAD was studied by cell proliferation analysis, cell apoptosis analysis, cell migration and invasion analysis, and subcutaneous inoculation of animal models. At the same time, RNA-Seq, RNA pull-down, ChIRP, ChIP, and luciferase reporter gene assays were performed to clarify the mechanism. RESULTS: The expression of LINC00958 in LUAD tissues was significantly upregulated when compared with that in adjacent tissues and could independently predict poor survival of patients with LUAD. LINC00958 knockdown significantly inhibited the growth and metastasis of lung cancer cells in vitro and in vivo. LINC00958 localized to the nucleus, regulated oncogenes and metabolism-related and immune response-related genes, and interacted with histones. The targets of LINC00958 were TRPV3, STAP2, and EDN2 promoters with motifs of HOXA1, NANOG, FOSL2, JUN, and ATF4. Moreover, HOXA1 overexpression mitigated the LINC00958 knockdown-induced oncogenic phenotype. MYC/MAX motif, which was detected at the cis-element of LINC00958, trans-activated the LINC00958 promoter. CONCLUSIONS: MYC/MAX-trans-activated LINC00958 promotes the malignant behavior of LUAD by recruiting HOXA1 and inducing oncogenic reprogramming.

Knockdown of TRIM66 inhibits malignant behavior and epithelial-mesenchymal transition in non-small cell lung cancer.

OBJECTIVE: The tripartite motif 66(TRIM66) is an important member of the TRIM protein superfamily, which can participate in the expression of multiple proteins, and is closely associated with the behaviors of non-small cell lung cancer (NSCLC). In this study, we aimed to explore the effect of TRIM66 in this process in vitro using NSCLC cell lines, and the role of TRIM66 in regulating epithelial-mesenchymal transition(EMT) in NSCLC. METHODS: Western blotting was used to detect the TRIM66 protein expression levels in NSCLC cell lines and normal lung epithelial cells BEAS-2B. We silenced its expression in A549 cells by transient siRNA transfection to ascertain the function of TRIM66 in NSCLC cells. Western blotting was used to detect the expression of EMT-related proteins. RESULTS: TRIM66 protein content was highest in NSCLC cell line A549, compared with BEAS-2B, it showed that the TRIM66-siRNA group lung cancer cell proliferation was significantly reduced after knockdown of TRIM66, and knockdown of TRIM66 also suppressed invasion, migration and clonogenic ability of A549 cells. Finally, we found that siRNA-mediated TRIM66 silencing suppressed EMT by downregulating expression of N-cadherin and vimentin and upregulating that of E-cadherin in NSCLC cells, which could effectively reduce the invasive, migratory, and proliferative capacities of lung cancer cells. CONCLUSION: Silence TRIM66 expression suppressed NSCLC cell proliferation, invasion, and migration. The siRNA-mediated TRIM66 silencing could block the occurrence of EMT. TRIM66 could be a promising novel target for future NSCLC treatments.

TRIM66 expression in non-small cell lung cancer: A new predictor of prognosis.

OBJECTIVE: The tripartite motif-containing protein (TRIM) family is involved in important biological processes such as the cell cycle, cell apoptosis, and innate immunity of virus. This study aimed to investigate TRIM66 expression and its predictive role in non-small cell lung cancer (NSCLC) patients. METHODS: We detected the expression levels of TRIM66 protein and TRIM66 mRNA in NSCLC tissues, and evaluated the prognostic role of TRIM66 in NSCLC. RESULTS: TRIMM66 was highly expressed in NSCLC tissues compared with normal paracancerous tissues (P= 0.001). The high TRIM66 expression closely associated with lymph node metastasis and TNM stage in NSCLC patients (P< 0.05). Kaplan-Meier survival model indicated that survival time of NSCLC patients in the high TRIM66 expression group were markedly lower than those in the low expression group (P< 0.05). Cox regression analysis showed that high expression of TRIM66 is associated with poor prognosis in NSCLC patients. CONCLUSION: TRIM66 can be serve as an important molecular marker for predicting the prognosis in NSCLC patients.