RESUMEN
The long non-coding RNA (lncRNA) TMEM44-AS1 is a novel lncRNA whose pro-carcinogenic role in gastric cancer and glioma has been demonstrated. However, its function in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we identified that TMEM44-AS1 was highly expressed in ESCC tissues and cells. Functionally, TMEM44-AS1 promoted ESCC cell proliferation, invasion and metastasis in vitro and in vivo. TMEM44-AS1 inhibited ferroptosis in ESCC cells, and ferroptosis levels were significantly increased after knockdown of TMEM44-AS1. Mechanistically, TMEM44-AS1 was positively correlated with GPX4 expression, and TMEM44-AS1 could bind to the RNA-binding protein IGF2BP2 to enhance the stability of GPX4 mRNA, thereby affecting ferroptosis and regulating the malignant progression of ESCC. In summary, this study reveals the TMEM44-AS1-IGF2BP2-GPX4 axis could influence cancer progression in ESCC. TMEM44-AS1 can be used as a potential treatment target against ESCC.
RESUMEN
Most of the existing metasurfaces are effective for the incident wave with the specific circularly polarized (CP) or linearly polarized (LP) state, that is the polarization-sensitive metasurface. This drawback dramatically hinders the practical use of the metasurface. Herein, this paper presents a strategy of polarization-insensitive transmissive microwave metasurfaces to manipulate the incident wave with arbitrary CP and LP states. The metasurface consists of polarization-insensitive unit cells. For the left circularly polarized (LCP) and right circularly polarized (RCP) incident waves, the same abrupt phase covering 0° to 360° can be realized by combining the Pancharatnam-Berry (PB) and resonant phases. As the arbitrary LP wave can decompose into the LCP and RCP waves, metasurfaces consisting of designed unit cells are valid for any polarization states. The polarization-insensitive transmissive microwave metalens and orbital angular momentum multiplexing metasurface working at 23 GHz are devised for verification. Simulation and measurement results verify the availability of the approach. The proposed method is suitable for designing microwave-transmissive metasurfaces capable of polarization insensitivity.
RESUMEN
Ten-eleven translocation proteins (TETs) are dioxygenases that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an important epigenetic mark that regulates gene expression during development and differentiation. Here, we found that the TET2 expression was positively associated with adipogenesis. Further, in vitro and in vivo experiments showed that TET2 deficiency blocked adipogenesis by inhibiting the expression of the key transcription factors CCAAT/enhancer-binding protein beta (C/EBPß), C/EBPα and peroxisome proliferator-activated receptor gamma (PPARγ). In addition, TET2 promoted 5hmC on the CpG islands (CGIs) of Cebpb, Cebpa and Pparg at the initial time point of their transcription, which requires the cAMP-responsive element-binding protein (CREB). At last, specific knockout of Tet2 in preadipocytes enabled mice to resist obesity and attenuated the obesity-associated insulin resistance. Together, TET2 is recruited by CREB to promote the expression of Cebpb, Cebpa and Pparg via 5hmC during adipogenesis and may be a potential therapeutic target for obesity and insulin resistance.
RESUMEN
Ferroptosis is an emerging form of non-apoptotic regulated cell death which is different from cell death mechanisms such as autophagy, apoptosis and necrosis. It is characterized by iron-dependent lipid peroxide accumulation. Circular RNA (circRNA) is a newly studied evolutionarily conserved type of non-coding RNA with a covalent closed-loop structure. It exhibits universality, conservatism, stability and particularity. At present, the functions that have been studied and found include microRNA sponge, protein scaffold, transcription regulation, translation and production of peptides, etc. CircRNA can be used as a biomarker of tumors and is a hotspot in RNA biology research. Studies have shown that ferroptosis can participate in tumor regulation through the circRNA molecular pathway and then affect cancer progression, which may become a direction of cancer diagnosis and treatment in the future. This paper reviews the molecular biological mechanism of ferroptosis and the role of circular RNA in tumors and summarizes the circRNA related to ferroptosis in tumors, which may inspire research prospects for the precise prevention and treatment of cancer in the future.
RESUMEN
BACKGROUND: Long non-coding RNA HOXC cluster antisense RNA 1 (HOXC-AS1) is a novel lncRNA whose cancer-promoting effect in gastric cancer and nasopharyngeal carcinoma has already been demonstrated. However, its functions in esophageal squamous cell carcinoma (ESCC) remains unknown. LncRNAs can interact with RNA-binding proteins (RBPs) and affect gene expression levels through post-transcriptional regulation. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a widely studied RBP, and sirtuin 1 also known as SIRT1 has been reported to be involved in cancer progression. METHODS: Establishment of in vivo models, HE and immunohistochemistry staining verified the oncogenic effect of HOXC-AS1. The interaction relationship between HOXC-AS1, IGF2BP2 and SIRT1 was verified by RNA pulldown and RNA immunoprecipitation (RIP) assay. Relative expression and stability changes of genes were detected by qPCR and actinomycin D experiments. Finally, the effect of HOXC-AS1-IGF2BP2-SIRT1 axis on ESCC was verified by rescue experiments. RESULTS: HOXC-AS1 is highly expressed in ESCC cells and plays oncogenic effects in vivo. qPCR showed the positive relationship between HOXC-AS1 and SIRT1 following HOXC-AS1 knockdown or overexpression. RNA-pulldown, mass spectrometry and RIP assay demonstrated that IGF2BP2 is an RBP downstream of HOXC-AS1. Then, RIP and qPCR showed that IGF2BP2 could bind to SIRT1 mRNA and knockdown IGF2BP2 resulted in decreased SIRT1 mRNA level. Finally, a series of rescue assay showed that the HOXC-AS1-IGF2BP2-SIRT1 axis can affect the function of ESCC. CONCLUSION: LncRNA HOXC-AS1 acts as an oncogenic role in ESCC, which impacts ESCC progression by interaction with IGF2BP2 to stabilize SIRT1 expression.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma de Células Escamosas de Esófago/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Sirtuina 1/genética , Neoplasias Esofágicas/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , ARN Mensajero , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Proliferación Celular/genéticaRESUMEN
BACKGROUND: TP53 is an important tumor suppressor gene on human 17th chromosome with its mutations more than 60% in tumor cells. Lung cancer is the highest incidence malignancy in men around the world. N-6 methylase (m6A) is an enzyme that plays an important role in mRNA splicing, translation, and stabilization. However, its role in TP53-mutant non-small-cell lung cancer (NSCLC) remains unknown. METHOD: First, we investigated 17 common m6A regulators' prognostic values in NSCLC. Then, after the establishment of risk signature, we explored the diagnostic value of m6A in TP53-mutant NSCLC. Finally, gene set enrichment analysis (GSEA), gene ontology (GO) enrichment analysis, and differential expression analysis were used to reveal the possible mechanism of m6A regulators affecting TP53-mutant NSCLC patients. RESULTS: Study showed that nine m6A regulators (YTHDC2, METTL14, FTO, METTL16, YTHDF1, HNRNPA2B1, RBM15, KIAA1429, and WTAP) were expressed differently between TP53-mutant and wild-type NSCLC (p < 0.05); and ALKBH5 and HNRNPA2B1 were associated with the prognostic of TP53-mutant patients. After construction of the risk signature combined ALKBH5 and HNRNPA2B1, we divided patients with TP53 mutations into high- and low-risk groups, and there was a significant survival difference between two groups. Finally, 338 differentially expression genes (DEGs) were found between high- and low-risk groups. GO enrichment analysis, PPI network, and GSEA enrichment analysis showed that m6A may affect the immune environment in extracellular and change the stability of mRNA. CONCLUSION: In conclusion, m6A regulators can be used as prognostic predictors in TP53-mutant patients.
Asunto(s)
Metiltransferasas/genética , Proteína p53 Supresora de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Biología Computacional , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Metilación , Mutación/genética , PronósticoRESUMEN
BACKGROUND: Long non-coding RNAs (lncRNAs) have been verified to play fatal role in regulating the progression of lung adenocarcinoma (LUAD). Although lncRNAs play important role in regulating the autophagy of tumor cells, the function and molecular mechanism of LINC01559 in regulating lung cancer development remain to be elucidated. METHOD AND MATERIALS: In this study, we used bioinformatics to screen out autophagy-related lncRNAs from TCGA-LUAD repository. Then the least absolute shrinkage and selection operator (LASSO) regression was applied to establish the signature of autophagy-related lncRNAs so that clinical characteristics and survival in LUAD patients be evaluated. Finally, we selected the most significant differences lncRNA, LINC01559, to verify its function in regulating LUAD progression in vitro. RESULTS: We found high expression of LINC01559 indicates lymph node metastasis and poor prognosis. Besides, LINC01559 promotes lung cancer cell proliferation and migration in vitro, by enhancing autophagy signal pathway via sponging hsa-miR-1343-3p. CONCLUSION: We revealed a novel prognostic model based on autophagy-related lncRNAs, and provide a new therapeutic target and for patients with lung adenocarcinoma named LINC01559.
RESUMEN
BACKGROUND: N-6 methylation (m6A) pushes forward an immense influence on the occurrence and development of lung adenocarcinoma (LUAD). However, the methylation on non-coding RNA in LUAD, especially long non-coding RNA (lncRNA), has not been received sufficient attention. METHODS: Spearman correlation analysis was used to screen lncRNA correlated with m6A regulators expression from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories, respectively. Then, the least absolute shrinkage and selection operator (LASSO) was applied to build a risk signature consisting m6A-related lncRNA. Univariate and multivariate independent prognostic analysis were applied to evaluate the performance of signature in predicting patients' survival. Next, we applied Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) to conduct pathway enrichment analysis of 3344 different expression genes (DEGs). Finally, we set up a competing endogenous RNAs (ceRNA) network to this lncRNA. RESULTS: A total of 85 common lncRNAs were selected to acquire the components related to prognosis. The final risk signature established by LASSO regression contained 11 lncRNAs: ARHGEF26-AS1, COLCA1, CRNDE, DLGAP1-AS2, FENDRR, LINC00968, TMPO-AS1, TRG-AS1, MGC32805, RPARP-AS1, and TBX5-AS1. M6A-related lncRNA risk score could predict the prognostic of LUAD and was significantly associated with clinical pathological. And in the evaluation of lung adenocarcinoma tumor microenvironment (TME) by using ESTIMATE algorithm, we found a statistically significant correlation between risk score and stromal/immune cells. CONCLUSION: M6A-related lncRNA was a potential prognostic and therapy target for lung adenocarcinoma.
Asunto(s)
Adenocarcinoma del Pulmón , Adenosina/análogos & derivados , Neoplasias Pulmonares , ARN Largo no Codificante , Microambiente Tumoral/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Adenosina/química , Adenosina/genética , Adenosina/metabolismo , Anciano , Biología Computacional , Metilación de ADN/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , ARN Largo no Codificante/química , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transcriptoma/genéticaRESUMEN
OBJECTIVE: To study the changes of dietary pattern among adult residents in different areas of Liaoning province from 1989 to 2006. METHODS: Healthy adults (6213 subjects) at age of 18 - 65 years from 480 households in three cities (Shenyang, Yingkou, Wafangdian) and three counties (Qingyuan, Huanren, Chaoyang) were selected with stratified multiple cluster random sampling. The information on nutrient intake of the subjects were collected from datasets of Chinese Health and Nutrition Survey conducted in 1989, 1991, 1993, 2000, 2004, and 2006. Different food intake, the nutrients intake percentages for recommended nutrition intake (RNI) and appropriate intake (AI), and the percentages of total energy and protein from grain, animal product, bean and its product were calculated to assess the residents' dietary pattern and nutrition status. The changes of dietary pattern among adult residents were analyzed. RESULTS: Among the residents, there were a 38.1% of decreased intake for grain (from 601.9 to 372.5 g/d), 20.5% for potato (from 75.6 to 60.1 g/d), 25.1% for beans (from 38.7 to 29.0 g/d), and a 77.2% of increased intake for fish and shrimp (from 25.0 to 44.3 g/d), 36.9% for livestock and poultry (from 65.6 to 89.8 g/d), 47.7% for fruit (from 70.7 to 104.4 g/d), and intake of milk product (from 5.8 to 21.3 g/d), egg (from 17.3 to 35.7 g/d), vegetable (from 296.1 to 316.3 g/d) were also increased from 1989 to 2006. During the period, the intake percentages of energy and protein from grain decreased from 67.5% (8.7 MJ/12.8 MJ per day) to 51.5% (5.0 MJ/9.6 MJ per day) and from 72.0% (66.2 g/91.9 g per day) to 59.7% (45.3 g/75.9 g per day), and on the contrary those from animal products increased from 8.9% (1.1 MJ/12.8 MJ per day) to 14.8 (1.4 MJ/9.6 MJ per day) and from 15.9% (14.6 g/91.9 g per day) to 27.9% (21.2 g/75.9 g per day), respectively. In 2006, the intake of vitamin A (508.9 µg/d) was 67.6% of it's RNI, intake of vitamin B(2) (0.9 mg/d) was 64.6% and the intake of calcium (453.7 mg/d) was 52.5% of it's AI among the residents. CONCLUSION: The intake of plant food decreased and that of animal food increased from 1989 to 2006 and the dietary intakes of calcium, vitamin A, vitamin B(2) need to be increased among adult population of Liaoning province.