BackgroundNon-small cell lung cancer (NSCLC) is a major subtype of lung cancer, with high mortality and limited treatment approaches. This paper explores the function of TAL1 in NSCLC progression and glycolysis and its mechanism.MethodsBioinformatics analysis screened out TAL1 and the upstream and downstream molecules. MTT, EdU, wound healing assay, Transwell assay, and TUNEL were utilized to detect the malignant phenotype of A549 and H460 cells. Western blot analysis was conducted to detect the expression of the proliferation-associated protein (Ki67), EMT-associated proteins (E-cadherin, N-cadherin), and glycolysis-associated proteins (GLUT1, LDHA, and PDK1). Cellular metabolism assays detected changes in glucose metabolites. A xenograft model was constructed, and the mouse tumor weight and volumes were measured periodically. Dual-luciferase assays and ChIP assays were performed to authenticate the transcriptional regulation of TAL1 on PKM2 and the relationship between DNMT3B and TAL1.ResultsTAL1 was lowly expressed in NSCLC, and TAL1 overexpression prevented the proliferation, migration, and invasion and elevated apoptosis. TAL1 inhibited PKM2 transcription, and overexpression of PKM2 reversed the trend of overexpression of TAL1 and promoted glycolysis. DNMT3B inhibited TAL1 expression through methylation modification. DNMT3B overexpression facilitated NSCLC cell growth and promoted glycolysis, and further overexpression of TAL1 reversed this trend. In vivo experiments showed that overexpression of TAL1 inhibited NSCLC progression, while combined overexpression of PKM2 promoted NSCLC progression. Overexpression of DNMT3B promoted NSCLC progression, and combined knockdown of PKM2 inhibited NSCLC progression.ConclusionDNMT3B activates glycolysis and promotes NSCLC progression by mediating methylation modification of TAL1 and inducing PKM2 transcription.

BackgroundNon-small cell lung cancer (NSCLC) is the predominant type of lung cancer and continues to be a major cause of cancer-related death globally. The identification of novel molecular targets is essential for developing effective therapeutic strategies.MethodsIn this study, we investigated the functional and mechanistic role of the E3 ubiquitin-protein ligase CBL in NSCLC progression. CBL expression was analyzed in NSCLC tumor tissues and cell lines using quantitative RT-PCR and Western blotting. The impact of CBL on NSCLC cell proliferation, migration, and invasion was assessed by a number of in vitro functional tests. Co-immunoprecipitation (Co-IP) and ubiquitination assays were performed to elucidate the molecular interaction between CBL and kinase insert domain receptor (KDR), a key mediator of angiogenesis.ResultsCBL expression was markedly reduced in NSCLC tissues and cell lines relative to normal equivalents. Gain- and loss-of-function tests demonstrated that CBL suppressed the NSCLC cell proliferation, migration, and invasion, highlighting its tumor-suppressive role. Mechanistically, CBL regulates KDR protein degradation via ubiquitination, thereby disrupting KDR-mediated signaling pathways associated with angiogenesis and tumor progression. Notably, overexpression of KDR reversed the anti-tumor effects of CBL, restoring the aggressive phenotype of NSCLC cells. These results suggest that CBL acts as a negative regulator of NSCLC malignancy through targeted degradation of KDR.ConclusionOur findings identify CBL as a functional tumor suppressor in NSCLC that exerts its anti-cancer effects via ubiquitin-mediated degradation of KDR. The CBL-KDR axis signifies a new regulatory route with significant therapeutic potential for NSCLC therapy.

1 8 6 / s 1 3 0 0 8 -0 2 4 -0 0 1 1 8 -w In this article [1], the FCM analysis representative image (Fig. 2D-control-plasmid group; Fig. 7B-PPP2R2Aplasmid + LY2940002 group) was incorrectly used by

BackgroundMETTL16 has recently emerged as an N6-methyladenosine (m6A) methyltransferase that serves an integral role in tumor regulation. However, its involvement in lung adenocarcinoma (LUAD) remains unexamined. This investigation aims to explore METTL16’s role and mechanism in LUAD progression.MethodsThe expression of METTL16 and G2 and S phase-expressed-1 (GTSE1) in LUAD was evaluated by qRT-PCR or western blotting. LUAD cell malignancy was checked by CCK-8, wound healing, and transwell invasion assays. The relationship among METTL16 and GTSE1 was determined via Pearson correlation analysis and MeRIP assay. The p53 pathway-related proteins were detected by western blotting, and cell cycle was analyzed by flow cytometry.ResultsMETTL16 was elevated in LUAD, and its silencing significantly reduced LUAD cell proliferation, migration, and invasion. GTSE1 was significantly downregulated upon silencing METTL16. Furthermore, increased levels of GTSE1 mRNA and protein were found in LUAD, and it was correlated positively with METTL16 in LUAD tissues. The stability of GTSE1 was modulated by METTL16 in an m6A-dependent way, and GTSE1 overexpression partially rescued the suppressive effects METTL16 silencing on LUAD cells. In addition, GTSE1 overexpression also inhibited p53 pathway to promote LUAD cell cycle.ConclusionsThese results indicate that METTL16-mediated m6A modification of GTSE1 accelerates LUAD progression by regulating p53 pathway and cell cycle. The aforementioned findings suggest METTL16 and GTSE1 may serve as potential targets for LUAD management.

BackgroundSeveral studies have delineated that dysregulated N6-methyladenosine (m6A) regulators participate in glioma progression. The objective of this study is to investigate the mechanism of Wilms’ tumor 1-associating protein (WTAP)-mediated m6A modification of long noncoding RNA (lncRNA) LINC00200 in glioma.MethodsThe LINC00200 expression in glioma was analyzed by qRT-PCR. The expressions of WTAP and Wnt/β-catenin pathway associated proteins were determined via qRT-PCR or western blotting. The levels of WTAP-mediated m6A modification of LINC00200 was ascertained by MeRIP-qPCR. Functionally, the effects of LINC00200 knockdown and the interaction of WTAP with LINC00200 on the glioma cell characteristics were examined by CCK8, colony formation, and transwell migration/invasion assays. In vivo experiments were performed to verify the effect of LINC00200 on tumor growth.ResultsLINC00200 was overexpressed in glioma, and high LINC00200 level was related to higher-grade tumor. Moreover, its knockdown inhibited the malignant properties and expression of molecules related to Wnt/β-catenin pathway in glioma cell lines. In vivo, LINC00200 knockdown attenuated tumor growth. WTAP was also overexpressed in glioma tissues and demonstrated a positive association with LINC00200 expression. Furthermore, the relative enrichment of LINC00200 m6A was enhanced/reduced in a WTAP-dependent manner. Meanwhile, silencing LINC00200 partially reversed the malignant effects of WTAP overexpression in glioma.ConclusionThese results demonstrate that WTAP-mediated m6A modification of LINC00200 promotes glioma progression by modulating Wnt/β-catenin pathway.

ObjectiveRegulatory Factor X (RFX) transcription factors have been implicated in different cancers. Ras association domain family (RASSF) has been shown clinical significance in lung cancer. This paper was to investigate the interaction of RFX2 and RASSF1 in lung adenocarcinoma (LUAD).MethodsThe transcriptome differences of LUAD patients in GSE32863, GSE43458, and GSE21933 datasets were analyzed. A-549 and NCI-H358 cell lines after overexpression of RFX2 were co-cultured with activated CD8+ T cells, and the release of IFN-γ, GZMB, PRF1 by CD8+ T cells, and PD-L1 in the LUAD cells were detected. Cell viability, invasion, and apoptosis were analyzed by CCK-8, Transwell, and TUNEL assays. Dual-luciferase assay and ChIP were conducted to detect the interaction between RFX2 and RASSF1 promoter. An in vivo tumor model was constructed to monitor tumor growth. YAP protein levels and phosphorylation were measured. A-549 and NCI-H358 cells treated with DMSO or PY-60 after RFX2 overexpression were co-cultured with activated CD8+ T cells.ResultsRFX2 was notably downregulated in LUAD. RFX2 overexpression increased infiltrating CD8+ T cells within transplanted tumors and inhibited immune escape, proliferation, and invasion of LUAD cells. RFX2 was enriched in the RASSF1 promoter, and RFX2 activated RASSF1 transcription by binding to the RASSF1 promoter. RASSF1 knockdown reversed the ability of RFX2 overexpression to inhibit immune escape. RFX2 depletion downregulated RASSF1, which reduced YAP phosphorylation, thus affecting the Hippo pathway to promote the immune escape.ConclusionRFX2 Loss in LUAD downregulates RASSF1 expression and YAP phosphorylation, thereby promoting immune escape through Hippo signaling.

MicroRNAs (miRNAs) are small, noncoding RNA molecules that play a vital role in regulating gene expression, especially in the differentiation of mesenchymal stem cells (MSCs) into vascular smooth muscle cells (VSMCs). MSCs hold considerable promise for vascular repair and regenerative medicine, given their ability to differentiate into smooth muscle cells (SMCs) under specific molecular cues. Recent studies have shown that miRNAs, through complex regulatory networks, influence MSC differentiation by targeting essential signaling pathways and modulating the expression of differentiation markers, underscoring the intricate roles of these molecules in cellular development.This review comprehensively examines the functions of various miRNAs in MSC differentiation, focusing on miR-143 and miR-145, which are upregulated by transforming growth factor beta 1 (TGF-β1), a key growth factor in SMC development. These miRNAs enhance differentiation by promoting the expression of SMC markers, including α-smooth muscle actin (α-SMA) and calponin, and by inhibiting factors that preserve MSCs in an undifferentiated state. This review further discusses the roles of miR-503, which supports SMC differentiation through SMAD7 inhibition via the TGF-β pathway, and miR-222-5p, which counteracts differentiation by downregulating ROCK2 and α-SMA. By highlighting these regulatory mechanisms, this review aims to clarify the bidirectional and multifaceted role of miRNAs in VSMC differentiation. This study offers insights into the therapeutic potential of miRNA-mediated MSC differentiation for vascular repair and regeneration, ultimately contributing to improved cardiovascular outcomes.

BackgroundCircular RNA (circRNA) and extracellular vesicles (EVs) in tumors are crucial for the malignant phenotype of tumor cells. Nevertheless, the mechanisms and clinical effects of EV-delivered hsa_circ_0090081 in gastric cancer (GC) are unclear. This study aimed to reveal the effect of eukaryotic translation initiation factor 4A3 (EIF4A3)-mediated hsa_circ_0090081 expression and EV-delivered hsa_circ_0090081 on GC progression.MethodsqRT-PCR was conducted to clarify hsa_circ_0090081 and EIF4A3 levels in GC tissues. Transmission electronic microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting identified the EVs isolated from GC cells by ultracentrifugation. The roles of hsa_circ_0090081, EIF4A3, and EV-delivered hsa_circ_0090081 in GC cells were analyzed using Transwell, EdU, and CCK-8 assays. The regulatory role between EIF4A3 and hsa_circ_0090081 was investigated using RIP, qRT-PCR, and Pearson’s analysis.ResultsOur study showed that hsa_circ_0090081 and EIF4A3 were highly expressed in GC, and hsa_circ_0090081 was associated with poor prognosis. Data revealed that hsa_circ_0090081 inhibition restrained GC cell proliferation, invasion, and migration. Additionally, EIF4A3 could bind to the pre-mRNA of PHEX (linear form of hsa_circ_0090081) to enhance hsa_circ_0090081 expression in GC cells. Moreover, EIF4A3 overexpression nullified the malignant phenotypic suppression caused by hsa_circ_0090081 silencing in GC cells. Furthermore, EVs secreted by GC cells delivered hsa_circ_0090081 to facilitate the malignant progression of targeted GC cells.ConclusionThis study showed that hsa_circ_0090081 was enhanced by EIF4A3 to play a promotive role in GC development. The results may help understand the mechanism of EIF4A3 and EV-delivered hsa_circ_0090081 and offer a valuable GC therapeutic target.

BackgroundThe precise mechanisms underlying preeclampsia (PE) pathogenesis remain unclear. Mesenchymal stem cells (MSCs) are involved in the pathology of PE. The aim of our study was to identify the effects of protein phosphatase 2 regulatory subunit B α (PPP2R2A) on MSCs and ascertain its latent role in the progression of PE.MethodsReverse-transcription quantitative polymerase chain reaction and western blot analyses were performed to determine the expression of PPP2R2A in decidual tissue and decidual (d)MSCs from healthy pregnant women and patients with PE as well as the expression levels of Bax and Bcl-2 in dMSCs. The levels of p-PI3K, PI3K, p-AKT, and AKT were determined using western blotting. Cell growth, apoptosis, and migration were analyzed using MTT, flow cytometry, and Transwell assays, respectively. Human umbilical vein endothelial cell (HUVEC) tube formation ability was assayed using a HUVEC capillary-like tube formation assay.ResultsPPP2R2A was downregulated in decidual tissues and dMSCs of patients with PE when compared with that in healthy pregnant women. Moreover, upregulation of PPP2R2A enhanced cell proliferation, reduced apoptotic dMSC, inhibited Bax expression, and increased Bcl-2 levels. Conditioned medium from PPP2R2A-overexpressing dMSCs promoted HTR-8/SVneo cell migration and angiogenesis of HUVEC. Furthermore, the PPP2R2A plasmid suppressed PI3K/AKT pathway activation in dMSCs. However, these effects were partially reversed by LY2940002 treatment.ConclusionPPP2R2A inhibition contributes to PE by regulating the proliferation, apoptosis, and angiogenesis of MSCs, providing a new therapeutic target for PE diagnosis and treatment.