Low‐level EFCAB1 promoted progress by upregulated DNMT3B and could be as a potential biomarker in lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) incidence is on the rise. We found that EFCAB1 (EF‐Hand Calcium Binding Domain 1) was significantly downregulated in LUAD tissues, but the mechanism of EFCAB1 is unknown.MethodsOne hundred and two LUAD samples and corresponding NT samples were prospectively collected from patients at the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, from August 2018 to August 2021.EFCAB1 expression was estimated in LUAD cells and tissues by qPCR. In‐vitro cytology assays were used to detect the role of EFCAB1 in LUAD cells.ResultsEFCAB1 expression level of LUAD was significantly lower than it''s adjacent cancer tissues and that of LUAD with big tumor size (>2 cm) was significantly lower than that of small tumor size (≤2 cm) group. It shown that expression levels of EFCAB1 from A549, HCC827, PC9 were lowly expressed. The cell migration, invasion, colony formation, proliferation ability of EFCAB1 OE A549, PC9 were lower than that of EFCAB1 OE A549, PC9 NC group, while the apoptotic cells percentage of the EFCAB1 OE A549, PC9 group were significantly increased. We found that DNMT1 mRNA expression level of PC9 was higher than that of BEAS‐2B, while these of A549, HCC827 decreased. Compared with BEAS‐2B, DNMT3A mRNA expression level of PC9 increased. DNMT3B mRNA expression level of PC9, HCC827 were higher than these of BEAS‐2B.ConclusionThe EFCAB1 mRNA in LUAD patients and cell lines were downregulated; EFCAB1 overexpression inhibited cell proliferation, migration, invasion, while promoted apoptosis. EFCAB1 was expected to become a biomarker of LUAD.     

Aberrant expression of HIF3A in plasma of patients with non‐small cell lung cancer and its clinical significance

BackgroundHypoxia‐inducible factors (HIFs) have been evaluated in various cancers and diseases. However, the specific role of hypoxia‐inducible factor 3 alpha (HIF3A) in non‐small cell lung cancer (NSCLC) remains controversial.Materials and MethodsWe investigated HIF3A mRNA expression in the plasma and tumor tissues of patients with NSCLC and explored its clinical significance. Plasma samples from 103 cases of lung adenocarcinoma (LUAD) and 96 cases of lung squamous cell carcinoma (LUSC), and tumor‐adjacent normal tissues from 58 LUAD and 62 LUSC cases were retrospectively evaluated at the No.8 People''s Hospital of Qing Dao. HIF3A expression was explored using RT‐qPCR. The clinical significance of HIF3A was evaluated in the plasma and tumor tissues using the receiver operating curve (ROC) and the area under the curve (AUC).ResultsHypoxia‐inducible factor 3 alpha expression was notably downregulated in the plasma or tumor tissues of patients with LUAD and LUSC, compared with the healthy control group or adjacent normal tissues. Furthermore, HIF3A expression had a significant positive correlation in the plasma and tumor tissues of LUAD and LUSC patients. Meanwhile, the ROC‐AUCs achieved a significantly higher range, from 0.84 to 0.93, with the plasma or tumor tissues of NSCLC patients. Thus, HIF3A expression was not only correlated with plasma and tumor tissues, but also showed potential significance in NSCLC.ConclusionHypoxia‐inducible factor 3 alpha is aberrantly detectable in NSCLC patients in the plasma and tumor tissues. HIF3A may be involved in hypoxic responses during the development and occurrence of NSCLC.     

Super enhancer‐LncRNA SENCR promoted cisplatin resistance and growth of NSCLC through upregulating FLI1

BackgroundSuper enhancer‐lncRNA smooth muscle and endothelial cell‐enriched migration/differentiation‐associated lncRNA (SENCR) were highly overexpressed in cisplatin‐resistant A549/DDP cells, while the mechanism was unclear.MethodsSE‐lncRNA SENCR and FLI1 mRNA expression in A549/DDP cell, LAD tissues were detected. SENCR knockdown of A549/DDP cell and SENCR overexpression of cisplatin‐sensitive A549 cell were constructed. Experiments of cell‐confirmed function of SENCR and the correlation between SENCR and FLI1 were validated.ResultsThe expression of SENCR and FLI1 mRNA in A549/DDP cell were both upregulated and mainly localized in the nucleus. Compared with DDP‐sensitive tissues with disease relief, SENCR expression was higher in DDP‐resistant tissues with disease progression from LAD. Knockdown of SENCR in A549/DDP reduced proliferation ability and cisplatin resistance, consistent with the decreased levels of proteins PCNA, MDMX, and P‐gp. Besides, whatever without cisplatin or with 2 μg/ml cisplatin, knockdown of SENCR reduced the migration, invasion, and colony formation abilities of A549/DDP cell and promoted apoptosis. However, when SENCR was overexpressed in A549 cell, all above results were reversed. Mechanistically, FLI1 expression was reduced after knocking down SENCR, while overexpressing SENCR increased FLI1 expression.ConclusionSE‐LncRNA SENCR was upregulated in A549/DDP, which could promote cisplatin resistance and growth of NSCLC cell through upregulating FLI1 expression.     

Bioinformatics analysis of differentially expressed miRNAs in non‐small cell lung cancer

ObjectiveNon‐small cell lung cancer (NSCLC) contains 85% of lung cancer. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the largest NSCLC subgroups. The aim of the study was to investigate the underlying mechanism in developing more effective subtype‐specific molecular therapeutic procedures.MethodsA total of 876 specimens were used in this study: 494 LUAD tissues (ie, 449 LUAD tissues and 45 matched normal tissues) and 382 LUSC tissues (ie, 337 LUSC tissues and 45 matched normal tissues). The miRNA sequencing data were processed using R. The differential expressed miRNAs between lung cancer and normal tissues were analyzed using the limma package in R. Gene expression, Western blotting, hematoxylin and eosin staining, and luciferase assay were used to test LUAD and LUSC.ResultsLUAD and LUSC appear sharply distinct at molecular and pathological level. Let‐7a‐5p, miR‐338, miR‐375, miR‐217, miR‐627, miR‐140, miR‐147b, miR‐138‐2, miR‐584, and miR‐197 are top 10 relevant miRNAs and CLDN3, DSG3, KRT17, TMEM125, KRT5, NKX2‐1, KRT7, ABCC5, KRAS, and PLCG2 are top 10 relevant genes in NSCLC. At the same time, the miRNAs expression levels were also quite different between the two groups. Among the differential expressed miRNAs, let‐7a‐5p was significantly down‐regulated in LUAD while miR‐338 was markedly down‐regulated in LUSC. Bioinformatics analyses appeared that let‐7a‐5p directly targets high–molecular weight keratin 5 (KRT5) which were shown to be a strong risk factor for LUAD. And NK2 homeobox 1(NKX2‐1) which was associated with tumor progression in LUSC was identified as a target gene of miR‐338.ConclusionsDistinct profile of miRNAs can take a part in the development of LUAD and LUSC and thus could serve as a subtype‐specific molecular therapeutic target to protect against LUAD and LUSC.     

MiR‐133a‐3p attenuates resistance of non‐small cell lung cancer cells to gefitinib by targeting SPAG5

BackgroundGefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI), clinically used to treat patients with non‐small cell lung cancer driven by EGFR mutations. Unfortunately, EGFR‐TKI resistance has become a clinical problem for the effective treatment of NSCLC patients. The purpose of this study was to explore the effect and mechanism of miR‐133a‐3p on the gefitinib sensitivity of NSCLC cells.MethodsThe gefitinib‐resistant PC9 (PC9/GR) cells were established through repeated long‐term exposure to gefitinib for half a year. Then, PC9/GR cells were transfected with miR‐133a‐3p mimics and PC9 cells were transfected with miR‐133a‐3p inhibitors to increase or decrease the expression of miR‐133a‐3p. CCK‐8 assay, colony formation assay, and caspase‐3 activity assay were employed to detect cell resistance to gefitinib. Quantitative real‐time PCR and Western blotting were used to evaluate the levels of miR‐133a‐3p, SPAG5, and other related genes. Starbase database was used to predict the target gene of miR‐133a‐3p and the prognosis of NSCLC patients. Target gene of miR‐133a‐3p was verified through dual‐luciferase reporter gene assay.ResultsMiR‐133a‐3p was significantly downregulated in gefitinib‐resistant cell line PC9/GR vs. gefitinib‐sensitive cell line PC9. Overexpression of miR‐133a‐3p increased the sensitivity of NSCLC cells to gefitinib and vice versa. Furthermore, SPAG5 is an important target gene of miR‐133a‐3p, and SPAG5 can reverse miR‐133a‐3p‐mediated gefitinib sensitivity of NSCLC cells.ConclusionsThese findings indicated that miR‐133a‐3p/SPAG5 axis played a vital role in acquired resistance to gefitinib in NSCLC cells, and miR‐133a‐3p may represent a potential therapeutic strategy for the treatment of human NSCLC.     

MiR‐630 suppresses non‐small cell lung cancer by targeting vimentin

ObjectiveThis study aimed to clarify the function of miR‐630 on non‐small cell lung cancer (NSCLC) cells.MethodsQuantitative real‐time PCR was utilized to detect the mRNA expression of miR‐630 and vimentin (VIM) in NSCLC tissues and cells. The protein expression of VIM, P53, Caspase‐3, Bcl‐2, Bax and JAK2/STAT3 was evaluated via Western blot. Dual‐luciferase reporter assay was applied to evaluate whether VIM is the target gene of miR‐630. The migration, invasion, proliferation and apoptosis of NSCLC cells were examined by wound‐healing assay, transwell assay, CCK‐8 assay, and flow cytometry, respectively.ResultsMiR‐630 was lowly expressed in NSCLC tissues and cells, while VIM was highly expressed in NSCLC cells. Dual‐luciferase reporter assay data validated that miR‐630 directly targeted VIM. MiR‐630 overexpression inhibited VIM expression, but the inhibition of miR‐630 upregulated VIM expression. Besides, miR‐630 mimics restrained cell migration, invasion, and proliferation, and promoted NSCLC cell apoptosis. Whereas, VIM overexpression partly attenuated the inhibitory effect of miR‐630 on NSCLC cells. Moreover, miR‐630 mimics impeded p‐JAK2 and p‐STAT3 protein expression; and miR‐630 inhibitor upregulated p‐STAT3 and VIM protein expression, which was reversed after the addition of STAT3 inhibitor C188‐9.ConclusionMiR‐630 constrained the progression of NSCLC by inhibiting JAK2/STAT3 pathway and downregulating VIM expression.     

Circular RNA hsa_circ_0011298 enhances Taxol resistance of non‐small cell lung cancer by regulating miR‐486‐3p/CRABP2 axis

BackgroundCircular RNAs (circRNAs) serve as critical regulators in the chemoresistance of human cancers, including non‐small cell lung cancer (NSCLC). We aimed to explore the role of hsa_circ_0011298 (circ_0011298) and its mechanism in Taxol resistance of NSCLC.MethodsCirc_0011298, microRNA‐486‐3p (miR‐486‐3p), and CRABP2 mRNA expression were determined using qRT‐PCR. EdU and MTT assays were used to detect cell proliferation. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Cell migratory and invasive abilities were detected using transwell assay. Cellular glycolysis was determined by specific kits. Protein levels were examined by western blot. Dual‐luciferase reporter and RIP assays were performed to confirm the relationship between miR‐486‐3p and circ_0011298 or CRABP2. Xenograft mice model was established to confirm the function of circ_0011298 in vivo.ResultsCirc_0011298 was overexpressed in Taxol‐resistant NSCLC cells and tissues. Circ_0011298 knockdown enhanced Taxol sensitivity by decreasing cell proliferation, migration, invasion, and glycolysis and inducing apoptosis and cell cycle arrest in Taxol‐resistant NSCLC cells. Circ_0011298 was a sponge of miR‐486‐3p, and the impact of circ_0011298 silencing on Taxol resistance was rescued by miR‐486‐3p inhibition. Moreover, miR‐486‐3p directly targeted CRABP2, and miR‐486‐3p inhibited Taxol resistance by targeting CRABP2. Furthermore, circ_0011298 regulated CRABP2 expression through targeting miR‐486‐3p. Importantly, circ_0011298 interference elevated Taxol sensitivity of NSCLC in vivo.ConclusionCirc_0011298 elevated Taxol resistance of NSCLC by sponging miR‐486‐3p and upregulating CRABP2, providing a possible circRNA‐targeted therapy for NSCLC.     

Serum transfer RNA‐derived fragment tRF‐31‐79MP9P9NH57SD acts as a novel diagnostic biomarker for non‐small cell lung cancer

BackgroundtRNA‐derived fragments (tRFs) have been found to have a crucial function in the pathophysiology of cancers. However, the function of tRFs in non‐small cell lung cancer (NSCLC) is yet unknown. The goal of this study was to assess the tRF‐31‐79MP9P9NH57SD serum expression from NSCLC patients and to determine its diagnostic usefulness.MethodsBy using stem‐loop quantitative real‐time PCR, we were able to detect various tRF‐31‐79MP9P9NH57SD expressions in 96 NSCLC serum samples, 96 healthy controls, and 20 pairs of NSCLC serum samples pre‐ and post‐surgery (qRT‐PCR). After that, we analyzed its diagnostic effectiveness using the receiver operating characteristic (ROC) curve.ResultsSerum tRF‐31‐79MP9P9NH57SD expression was higher in NSCLC patients, and levels of tRF‐31‐79MP9P9NH57SD were linked to the clinical stage (p = 0.002) and the malignancy of lymph node (p = 0.012). In addition, after the procedure, the serum tRF‐31‐79MP9P9NH57SD expression in NSCLC patients dropped. With 48.96 percent sensitivity and 90.62 percent specificity, the area under ROC curve (AUC) was 0.733.Conclusionserum tRF‐31‐79MP9P9NH57SD possibly is a new and groundbreaking biomarker for the NSCLC.     

Expression and prognostic significance of m6A‐related genes in TP53‐mutant non‐small‐cell lung cancer

BackgroundTP53 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.MethodFirst, 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.ResultsStudy 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.ConclusionIn conclusion, m6A regulators can be used as prognostic predictors in TP53‐mutant patients.     

A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

BackgroundImmunotherapy was widely used for the treatment of non‐small cell lung cancer (NSCLC). However, whether inhibition of immune checkpoints individually or simultaneously could improve the therapeutic efficacy of NSCLC remains to be investigated. Here, we explored the aberrant levels of several checkpoints and evaluated their potential diagnostic values for NSCLC.MethodsSerum samples of 89 NSCLC patients and 57 healthy donors were collected from Nanjing Drum Tower Hospital between November 2019 and July 2020. Fourteen human immune checkpoints were quantified by Procarta‐Plex Human Immuno‐Oncology Checkpoint Panel.ResultsThe expression levels of sTIM‐3, sCD137, sCD27, sLAG‐3, sIDO, sPD‐L2, sCD152, sCD80, and sPD‐1 were all significantly increased in serum of NSCLC patients. Especially, sLAG‐3 was significantly elevated in serum of NSCLC patients at early‐stage (stages I and II), TIM‐3, CD137, and CD27 were significantly higher in the advanced NSCLC patients (stages III and IV) than in the early‐stage groups. Receiver operating characteristics (ROC) results showed that except for PD‐1, all the other immune checkpoint proteins had potential diagnostic values for NSCLC. sTIM‐3 had the highest diagnostic accuracy, followed by sLAG‐3. Combining sTIM‐3, sLAG‐3, and sCD137 could increase the accuracy to a higher level. Moreover, sCD27 was correlated with NSCLC cancer type, age, sex, and disease stage, while sCD137 was correlated with age and disease stage. sTIM‐3 and sIDO were correlated with stage and age, respectively.ConclusionsTIM‐3 and LAG‐3 were independent biomarkers for the early diagnosis of NSCLC. The combination of TIM‐3, LAG‐3, and CD137 could increase the diagnostic accuracy.     

miR‐423‐3p activates FAK signaling pathway to drive EMT process and tumor growth in lung adenocarcinoma through targeting CYBRD1

BackgroundLung adenocarcinoma (LUAD) is a malignant tumor with a high fatality rate and poor overall survival, while molecular targets diagnosing and alleviating lung cancer remain inadequate.MethodsIn this article, we highlighted the upregulation of microRNA‐423‐3p (miR‐423‐3p) in LUAD, especially in smokers aged over 40, and revealed that the high expression of miR‐423‐3p was significantly associated with smoker, age, and pathologic stage of LUAD patients.ResultsMoreover, overexpressing miR‐423‐3p could facilitate LUAD cell proliferation, invasion, adhesion, and epithelial–mesenchymal transition (EMT) process, while depleted miR‐423‐3p caused repressive influence upon it. Mechanically, we identified that miR‐423‐3p could activate FAK signaling pathway through binding to the 3''‐UTR of cytochrome B reductase 1 (CYBRD1). Furthermore, we demonstrated that CYBRD1 was lowly expressed in LUAD, and miR‐423‐3p overexpression could rescue the impairment of LUAD cell proliferation, invasion, adhesion, and EMT caused by CYBRD1 depletion. Noticeably, miR‐423‐3p depletion efficiently hindered LUAD tumor growth in vivo.ConclusionCollectively, our findings demonstrated that miR‐423‐3p/CYBRD1 axis could be regarded as a promising biomarker to alleviate the poor LUAD prognosis.     

miR‐548d‐3p inhibits the invasion and migration of gastric cancer cells by targeting GKN1

BackgroundThe aim of this study was to explore the function and mechanism of GKN1 in gastric cancer (GC) progression.MethodsFirstly, we used GEO2R to perform differential gene analysis on {"type":"entrez-geo","attrs":{"text":"GSE26942","term_id":"26942"}}GSE26942 and {"type":"entrez-geo","attrs":{"text":"GSE79973","term_id":"79973"}}GSE79973 and constructed the protein–protein interaction network of differential genes by STRING. Next, the cytoHubba, Mcode plugins, and GEPIA were used to obtain our follow‐up research object GKN1. Then, the function of GKN1 in GC was verified by scratch and transwell assay in GC cells. We further analyzed the genes related to GKN1 through LinkedOmics, and exported top 100 genes positively or negatively correlated with GKN1. Meanwhile, Metascape was performed on these genes. Finally, we analyzed the miRNAs that bind to GKN1 through the miRDB and verified the correlation between miR‐548d‐3p and GKN1 using dual‐fluorescence and quantitative PCR experiments.ResultsBioinformatics analysis showed that there were 52 differential genes on {"type":"entrez-geo","attrs":{"text":"GSE26942","term_id":"26942"}}GSE26942 and {"type":"entrez-geo","attrs":{"text":"GSE79973","term_id":"79973"}}GSE79973. In addition, the results of functional assays indicated that overexpressed GKN1 can inhibit GC cell migration and invasion, while GKN1 knockdown demonstrated the opposite effect. Additionally, Metascape analysis results showed that the 3′‐UTR region of mRNA is rich in AU sequences, based on which we infer that mRNA may be regulated by miRNA. Dual‐fluorescence and quantitative PCR assays clarified that miR‐548d‐3p may be one of the target miRNAs of GKN1, which was up‐regulated in GC tissues.ConclusionsIn summary, we clarified that miR‐548d‐3p regulates GKN1 to participate in GC cell migration and invasion, and provides a possible target for the prognostic diagnosis and treatment of GC.     

Plasma SNORD42B and SNORD111 as potential biomarkers for early diagnosis of non‐small cell lung cancer

BackgroundNon‐small‐cell lung cancer (NSCLC) still occupied the leading reason of cancer death due to lack of availability of early detection. This study aimed to identify the effective biomarkers for the early‐stage NSCLC diagnostics based on plasma snoRNAs.Materials and MethodsThe differential snoRNAs between lung cancer patients and healthy donors were analyzed using the SNORic and TCGA databases. SNORD42B and SNORD111 were screened out and further verified in 48 FFPE NSCLC and adjacent normal tissues, as well as in plasma from 165 NSCLC patients and 118 health donors using qRT‐PCR. Next, their diagnostic efficiency, as well as combined with carcinoembryonic antigen (CEA), was obtained by the analysis of receiver operating characteristic (ROC).ResultsWe first screened out 47 top differential snoRNAs, among which the top 10 upregulated snoRNAs in LUAD were U44, U75, U78, U77, SNORD72, SNORD13, SNORD12B, SCARNA5, U80, SNORD41, and in LUSC were U44, U75, U78, SNORD41, SNORD111, SNORA56, U17a, SNORD35A, SNORD32A, SNORA71D. SNORD42B and SNORD111 was significantly increased not only in tumor tissues but also in plasma from NSCLC and early‐stage NSCLC patients. They were capable to act as promising biomarkers for NSCLC and early‐stage NSCLC diagnosis. Moreover, CEA diagnostic efficiency for early‐stage NSCLC was significantly improved when combined with these two plasma snoRNAs.ConclusionSNORD42B and SNORD111 could act as the potential and non‐invasive diagnostic biomarkers for NSCLC and early‐stage NSCLC.     

Ameliorative effect and mechanism of Yi‐Suan‐Cha against hyperuricemia in rats

BackgroundThis study aimed to evaluate the urate‐lowering effects of Yi‐Suan‐Cha and explore its underlying mechanisms in experimental hyperuricemia induced in rats.MethodsForty‐eight male SD rats were randomly allocated into normal control, model, allopurinol, benzbromarone, low‐dose Yi‐Suan‐Cha (0.2 g/ml), and high‐dose Yi‐Suan‐Cha (0.4 g/ml) groups (n = 8 rats per group). Rat models of hyperuricemia were established through intragastric administration of adenine 25 mg/kg + potassium oxalate 300 mg/kg for 3 weeks. After the last administration, serum uric acid, creatinine, and urea nitrogen levels were measured. Renal histopathology was observed by hematoxylin‐eosin staining. Xanthine oxidase level in serum and liver homogenates was measured by ELISA. The protein and mRNA expression of URAT1, ABCG2, OAT1, and GLUT9 in the kidney was detected by Western blotting and RT‐PCR, respectively.ResultsThe serum uric acid levels were significantly lowered in all medication groups than in the model group. The benzbromarone and both Yi‐Suan‐Cha groups showed clear kidney structures with no obvious abnormalities. Compared with the normal control group, the model group showed increased URAT1/GLUT9 protein expression and decreased ABCG2/OAT1 protein expression. Compared with the model group, both Yi‐Suan‐Cha groups showed decreased URAT1/GLUT9 protein expression and increased ABCG2/OAT1 protein expression. Compared with that in the normal control group, URAT1/GLUT9 mRNA expression increased in the model group. Compared with the model group, the low‐dose and high‐dose Yi‐Suan‐Cha groups showed decreased URAT1/GLUT9 mRNA expression and increased ABCG2/OAT1 mRNA expression.ConclusionYi‐Suan‐Cha may lower uric acid level by downregulating URAT1/GLUT9 expression and upregulating ABCG2/OAT1 expression.     

Circular RNA circβ‐catenin aggravates the malignant phenotype of non‐small‐cell lung cancer via encoding a peptide

BackgroundMore and more evidences demonstrate that circular RNAs (circNRAs) can encode protein. As a circRNA with translation capabilities, outcomes of circβ‐catenin in non‐small cell lung cancer (NSCLC) still need to be explored.MethodThe research methods of circβ‐catenin in the article include qRT‐PCR, wound healing assay, CCK‐8, colony formation, and Transwell assay. Western blotting and immunofluorescence were provided to detect protein expression levels and peptide encoded by circβ‐catenin, respectively.ResultsA prominently higher circβ‐catenin expression was found in NSCLC tissues. Silencing of circβ‐catenin was able to inhibit NSCLC cell migrating, invasive, and proliferative phenotypes. Overexpression of circβ‐catenin could enhance the migrating, invasive, and proliferative phenotypes of NSCLC cells. Importantly, circβ‐catenin was found to encode a peptide in NSCLC cells. Silencing or overexpression of circβ‐catenin could reduce or increase β‐catenin protein expression via suppressing the degradation of β‐catenin.ConclusionCircβ‐catenin could promote NSCLC cell malignant phenotypes via peptide‐regulated β‐catenin pathway. Our study provided a new understanding for the mechanisms of NSCLC.     

Seven tumor‐associated autoantibodies as a serum biomarker for primary screening of early‐stage non‐small cell lung cancer

ObjectiveThe purpose of this study was to analyze the levels of tumor‐associated autoantibodies (TAAbs) in lung diseases and determine their diagnostic efficiency in early‐stage non‐small cell lung cancer (NSCLC).MethodsWe retrospectively analyzed the levels of 7‐TAAbs in 177 newly diagnosed early‐stage NSCLC patients, 202 patients with lung benign diseases and 137 healthy cases. The levels of a panel of 7‐TAAbs, including p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, GBU4‐5, were measured by ELISA.ResultsThe serum levels of p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, and GBU4‐5 were not statistically different among NSCLC, benign and healthy groups (p > 0.05). The area under the curve (AUC) of 7‐TAAbs was all lower than 0.70. The sensitivity of combined detection was the highest (23.73%), while the specificity was the lowest (88.79%). The positive rates of PGP9.5, SOX2, and combined detection were significantly different among the three groups (p < 0.05). Among them, PGP9.5 and combined detection were significantly different between the NSCLC and benign groups (p < 0.05), PGP9.5, SOX2 and combined detection were significantly different between the NSCLC and healthy groups (p < 0.05).ConclusionsThe diagnostic efficiency of 7‐TAAbs in early‐stage NSCLC was not high, so it cannot be used alone as a screening method for NSCLC.