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.

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.