Role of ventrolateral part of ventromedial hypothalamus in post-myocardial infarction cardiac dysfunction induced by sympathetic nervous system.

Psychological stress has been recognized as a contributing factor to worsened prognosis in patients with cardiac failure following myocardial infarction (MI). Although the ventrolateral part of the ventromedial hypothalamus (VMHVL) has been implicated in emotional distress, its involvement in post-MI cardiac dysfunction remains largely unexplored. This study was designed to investigate the effect of the VMHVL activation in the MI rat model and its underlying mechanisms. Our findings demonstrate that activation of VMHVL neurons enhances the activity of the cardiac sympathetic nervous system through the paraventricular nucleus (PVN) and superior cervical ganglion (SCG). This activation leads to an elevation in catecholamine levels, which subsequently modulates myosin function and triggers the release of anti-inflammatory factors, to exacerbate the post-MI cardiac prognosis. The denervation of the superior cervical ganglion (SGN) effectively blocked the cardiac sympathetic effects induced by the VMHVL activation, and ameliorated the cardia fibrosis and dysfunction. Therefore, our study identified the role of the "VMHVL-PVN-SCG" sympathetic pathway in the post-MI heart, and proposed SGN as a promising strategy in mitigating cardiac prognosis in stressful rats.

Increased sympathetic outflow induced by emotional stress aggravates myocardial ischemia-reperfusion injury via activation of TLR7/MyD88/IRF5 signaling pathway.

BACKGROUND AND OBJECTIVE: Emotional stress substantially increases the risk of ischemic cardiovascular diseases. Previous study indicates that sympathetic outflow is increased under emotional stress. We aim to investigate the role of increased sympathetic outflow induced by emotional stress in myocardial ischemia-reperfusion (I/R) injury, and explore the underlying mechanisms. METHODS AND RESULTS: We used Designer Receptors Exclusively Activated by Designer Drugs technique to activate the ventromedial hypothalamus (VMH), a critical emotion-related nucleus. The results revealed that emotional stress stimulated by VMH activation increased sympathetic outflow, enhanced blood pressure, aggravated myocardial I/R injury, and exacerbated infarct size. The RNA-seq and molecular detection demonstrated that toll-like receptor 7 (TLR7), myeloid differentiation factor 88 (MyD88), interferon regulatory factor 5 (IRF5), and downstream inflammatory markers in cardiomyocytes were significantly upregulated. Emotional stress-induced sympathetic outflow further exacerbated the disorder of the TLR7/MyD88/IRF5 inflammatory signaling pathway. While inhibition of the signaling pathway partially alleviated myocardial I/R injury aggravated by emotional stress-induced sympathetic outflow. CONCLUSION: Increased sympathetic outflow induced by emotional stress activates TLR7/MyD88/IRF5 signaling pathway, ultimately aggravating I/R injury.

Long Noncoding RNA ZBED5-AS1 Facilitates Tumor Progression and Metastasis in Lung Adenocarcinoma via ZNF146/ATR/Chk1 Axis.

Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis, including lung adenocarcinoma (LUAD). However, the functional and regulatory mechanisms of lncRNAs in LUAD remain poorly understood. In this study, we investigated the role of lncRNA ZBED5-AS1 in LUAD. We found that ZBED5-AS1 was upregulated in LUAD specimens and overexpressed in LUAD cell lines. ZBED5-AS1 promoted LUAD cell proliferation, migration, and invasion in vitro and promoted LUAD cell growth in vivo. ZBED5-AS1 promoted ZNF146 expression, activating the ATR/Chk1 pathway and leading to LUAD progression. We observed that exosomes from LUAD cells have a higher expression of ZBED5-AS1 compared with exosomes from the normal cell line BEAS-2B. Coculture experiments with exosomes showed that ZBED5-AS1 expression was downregulated after coculture with Si-ZBED5-AS1 exosomes, and coculture with exosomes with low ZBED5-AS1 expression inhibited proliferation and invasion of LUAD cells. Our results indicate that ZBED5-AS1 functions as an oncogenic factor in LUAD cells by targeting the ZNF146/ATR/Chk1 axis.

Melatonin improves cardiac remodeling and brain-heart sympathetic hyperactivation aggravated by light disruption after myocardial infarction.

Light in the external environment might affect cardiovascular function. The light disruption seems to be related to changes in cardiovascular physiological functions, and disturbing light may be a risk factor for cardiovascular diseases. Prior studies have found that light disruption after myocardial infarction (MI) exacerbates cardiac remodeling, and the brain-heart sympathetic nervous system may be one of the key mechanisms. However, how to improve light-disrupted cardiac remodeling remains unclear. Melatonin is an indoleamine secreted by the pineal gland and controlled by endogenous circadian oscillators within the suprachiasmatic nucleus, which is closely associated with light/dark cycle. This study aimed to explore whether melatonin could improve light-disrupted cardiac remodeling and modulate the brain-heart sympathetic nervous system. Our study revealed that light disruption reduced serum melatonin levels, aggravated cardiac sympathetic remodeling, caused overactivation of the brain-heart sympathetic nervous system, exacerbated cardiac dysfunction, and increased cardiac fibrosis after MI, while melatonin treatment improved light disruption-exacerbated cardiac remodeling and brain-heart sympathetic hyperactivation after MI. Furthermore, RNA-Seq results revealed the significant changes at the cardiac transcription level. In conclusion, melatonin may be a potential therapy for light-disrupted cardiac remodeling.

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

BACKGROUND: Super 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. METHODS: SE-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. RESULTS: The 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. CONCLUSION: SE-LncRNA SENCR was upregulated in A549/DDP, which could promote cisplatin resistance and growth of NSCLC cell through upregulating FLI1 expression.

Low-level gastrokine 2 promoted progress of NSCLC and as a potential biomarker.

BACKGROUND: Gastrokine 2 (GKN2) is significantly downregulated in non-small cell lung cancer (NSCLC) tissues than in normal tissues (NT), as assessed by mRNA microassay; however, the mechanism and clinical value of GKN2 is unknown in NSCLC. METHODS: A total of 60 NSCLC samples and corresponding NT samples were prospectively collected GKN2 expression in NSCLC tissues was estimated. Also, the expression level of GKN2 promoter methylation and correlation with clinical data in NSCLC patients from public databases were analyzed. Cytology experiments were also carried out. RESULTS: The GKN2 mRNA and protein expression level in NSCLC was significantly lower than that in the NT, and the GKN2 expression level in large tumors NSCLC was significantly lower than that in the small tumor group. Public data showed that expression of GKN2 in LUAD with P53 mutation group was lower than that of the P53 non-mutation group, and GKN2 promoter methylation level of LUAD was significantly higher than its NT and close to age and clinical stage. Cell migration, invasion, and proliferation ability of GKN2 overexpressed were lower in A549 and PC9 groups than those in GKN2 overexpressed A549 and PC9 negative control groups, while the percentage of apoptotic cells increased in the GKN2 overexpressed A549 and PC9 groups. The DNMT3B mRNA expression levels were higher in PC9 and A549 cells than BEAS-2B cells. CONCLUSION: The overexpression of GKN2 significantly inhibited cell proliferation, migration, and invasion and promoted apoptosis. Low-level GKN2 promoted the progression of NSCLC via DNMT3B and is expected to be a biomarker for NSCLC.

Construction and analysis of expression profile of exosomal lncRNAs in pleural effusion in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a highly malignant tumor with a very low five-year survival rate. In this study, we aimed to identify differentially expressed long-chain non-coding RNA (lncRNAs) and mRNAs from benign and malignant pleural effusion exosomes. METHODS: We used gene microassay and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect and verify differentially expressed mRNAs and lncRNAs in benign and malignant pleural effusion exosomes. Gene Ontology (GO) functional significance and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway significance enrichment analyses were performed to identify the difference in biological processes and functions between different mRNAs. We selected the lncRNA ZBED5-AS1 with an upregulated differential fold of 3.003 and conducted a preliminary study on its cellular function. RESULTS: Gene microassay results revealed that 177 differentially expressed lncRNAs were upregulated, and 215 were downregulated. The top 10 upregulated were FMN1, AL118505.1, LINC00452, AL109811.2, CATG00000040683.1, AC137932.1, AC008619.1, AL450344.1, AC092718.6, and ZBED5-AS1. The top 10 downregulated were TEX41, G067726, JAZF1-AS1, AC027328.1, AL445645.1, AL022345.4, AC008572.1, AC123777.1, AC093714.1, and PHKG1. For the mRNAs, 79 were upregulated, and 123 were notably downregulated. GO analysis revealed that the upregulated differential mRNAs were mainly involved in "cellular response to acidic pH" (biological processes), "endoplasmic reticulum part" (cellular components), and "at DNA binding, cyclase activity" (molecular functions). KEGG pathways were found to be related to V. cholerae infection, Parkinson's disease, and cell adhesion molecules. RT-qPCR showed that ZBED5-AS1 was highly expressed in LUAD tissues, cells, and benign and malignant pleural fluid exosomes. Overexpression of ZBED5-AS1 could significantly promote the proliferation, migration, invasion, and colony formation of LUAD cells, and knockdown had the opposite consequence. CONCLUSION: The pleural effusion exosomes from patients with LUAD include several improperly expressed genes, and lncRNA-ZBED5-AS1 is a new biomarker that aids in our understanding of the occurrence and progression of LUAD.

Panchromatic Image Super-Resolution Via Self Attention-Augmented Wasserstein Generative Adversarial Network.

Panchromatic (PAN) images contain abundant spatial information that is useful for earth observation, but always suffer from low-resolution ( LR) due to the sensor limitation and large-scale view field. The current super-resolution (SR) methods based on traditional attention mechanism have shown remarkable advantages but remain imperfect to reconstruct the edge details of SR images. To address this problem, an improved SR model which involves the self-attention augmented Wasserstein generative adversarial network ( SAA-WGAN) is designed to dig out the reference information among multiple features for detail enhancement. We use an encoder-decoder network followed by a fully convolutional network (FCN) as the backbone to extract multi-scale features and reconstruct the High-resolution (HR) results. To exploit the relevance between multi-layer feature maps, we first integrate a convolutional block attention module (CBAM) into each skip-connection of the encoder-decoder subnet, generating weighted maps to enhance both channel-wise and spatial-wise feature representation automatically. Besides, considering that the HR results and LR inputs are highly similar in structure, yet cannot be fully reflected in traditional attention mechanism, we, therefore, designed a self augmented attention (SAA) module, where the attention weights are produced dynamically via a similarity function between hidden features; this design allows the network to flexibly adjust the fraction relevance among multi-layer features and keep the long-range inter information, which is helpful to preserve details. In addition, the pixel-wise loss is combined with perceptual and gradient loss to achieve comprehensive supervision. Experiments on benchmark datasets demonstrate that the proposed method outperforms other SR methods in terms of both objective evaluation and visual effect.

Analysis of lncRNA UCA1-related downstream pathways and molecules of cisplatin resistance in lung adenocarcinoma.

BACKGROUND: To analyze the lncRNA UCA1-related downstream pathways and molecules of cisplatin resistance in lung adenocarcinoma. METHODS: We constructed overexpression and siRNA vectors targeting UCA1 and TXNIP and then used next-generation sequencing to compare the UCA1 overexpression and negative control from A549 cell. RESULTS: It shown that 647 upregulated mRNAs and 633 downregulated differentially expressed mRNAs-related UCA1, and the top ten upregulated mRNAs were CPD, AC007192.1, TGOLN2, LGR4, TFPI, CYP1B1, TOMM6, HLA-B, SLC35F6, and TOP2A, and top ten downregulated mRNAs were TXNIP, SESN2, STC2, HSPA1A, MMP10, CHAC1, DNAJB1, AC004922.1, ATF3, and GABARAPL1. We found TXNIP mRNA expression level was the most significantly downexpressed mRNA. TXNIP mRNA expression level of LAD tissues was clearly lower than the adjacent tissues. UCA1 expression level of cisplatin insensitive group was markedly higher than that of cisplatin-sensitive group, while TXNIP mRNA expression level of cisplatin insensitive group was clearly lower than that of cisplatin-sensitive group. Compared to the BEAS-2B, TXNIP mRNA expression level cut down in A549 and A549/DDP cell and that of A549/DDP cell was lower than A549 cell. After UCA1 overexpression, TXNIP mRNA obviously decreased, while proliferation ability and IC50 of A549 heightened. After knocking down UCA1, TXNIP mRNA was significantly increased, while proliferation ability and IC50 of A549/DDP lowered. PPI analysis result showed that TXNIP could interact with multiple proteins such as TXN, DDIT4, and NLRP3. CONCLUSION: UCA1 promoted cisplatin resistance by downregulating TXNIP expression in LAD, and TXNIP could interact with multiple proteins. So, UCA1/TXNIP axis might affect cisplatin resistance in LAD.

RGB-IR Cross Input and Sub-Pixel Upsampling Network for Infrared Image Super-Resolution.

Deep learning-based image super-resolution has shown significantly good performance in improving image quality. In this paper, the RGB-IR cross input and sub-pixel upsampling network is proposed to increase the spatial resolution of an Infrared (IR) image by combining it with a color image of higher spatial resolution obtained with a different imaging modality. Specifically, this is accomplished by fusion of the features map of two RGB-IR inputs in the reconstruction of an infrared image. To improve the accuracy of feature extraction, deconvolution is replaced by sub-pixel convolution to upsample image in the network. Then, the guided filter layer is introduced for image denoising of IR images, and it can preserve the image detail. In addition, the experimental dataset, which is collected by us, contains large numbers of RGB images and corresponding IR images with the same scene. Experimental results on our dataset and other datasets demonstrate that the method is superior to existing methods in accuracy and visual improvement.

Infrared and visible image perceptive fusion through multi-level Gaussian curvature filtering image decomposition.

The aim of infrared and visible image fusion is to obtain an integrated image that contains obvious object information and high spatial resolution background information. The integrated image is more conductive for a human or a machine to understand and mine the information contained in the image. To attain this purpose, a fusion algorithm based on multi-level Gaussian curvature filtering (MLGCF) image decomposition is proposed. First, a MLGCF is presented and employed to decompose the input source images into three different layers: small-scale, large-scale, and base layers. Then, three fusion strategies-max-value, integrated, and energy-based-are applied to combine the three types of layers, which are based on the different properties of the three types of layers. Finally, the fusion image is reconstructed by summing the three types of fused layers. Six groups of experiments demonstrate that the proposed algorithm performs effectively in most cases by subjective and objective evaluations and even exceeds many high-level fusion algorithms.

Fusion of multi-focus images via a Gaussian curvature filter and synthetic focusing degree criterion.

The aim of multi-focus image fusion technology is to acquire an image of every scene all focused on the same visual point at different focal settings. To achieve this goal, we propose an improved multi-focus image fusion algorithm based on a Gaussian curvature filter and synthetic focusing degree criterion. First, in order to realize the salient feature extraction, a Gaussian curvature filter is applied to obtain the most sharpness regions. Then we obtain a coarse fusion map by composing a synthetic focusing degree criterion, which is a combination of the spatial frequency and the local variance of image. The coarse fusion map is further processed by morphological filters and median filters to acquire an optimized fusion map. Finally, the fusion image is obtained via a weighted fusion operation. Experimental results demonstrate that our proposed algorithm can be competitive with, or even outperform, many existing fusion methods on both qualitative and quantitative measures.

Multi-focus image fusion using a guided-filter-based difference image.

The aim of multi-focus image fusion technology is to integrate different partially focused images into one all-focused image. To realize this goal, a new multi-focus image fusion method based on a guided filter is proposed and an efficient salient feature extraction method is presented in this paper. Furthermore, feature extraction is primarily the main objective of the present work. Based on salient feature extraction, the guided filter is first used to acquire the smoothing image containing the most sharpness regions. To obtain the initial fusion map, we compose a mixed focus measure by combining the variance of image intensities and the energy of the image gradient together. Then, the initial fusion map is further processed by a morphological filter to obtain a good reprocessed fusion map. Lastly, the final fusion map is determined via the reprocessed fusion map and is optimized by a guided filter. Experimental results demonstrate that the proposed method does markedly improve the fusion performance compared to previous fusion methods and can be competitive with or even outperform state-of-the-art fusion methods in terms of both subjective visual effects and objective quality metrics.

Infrared and visible image fusion with spectral graph wavelet transform.

Infrared and visible image fusion technique is a popular topic in image analysis because it can integrate complementary information and obtain reliable and accurate description of scenes. Multiscale transform theory as a signal representation method is widely used in image fusion. In this paper, a novel infrared and visible image fusion method is proposed based on spectral graph wavelet transform (SGWT) and bilateral filter. The main novelty of this study is that SGWT is used for image fusion. On the one hand, source images are decomposed by SGWT in its transform domain. The proposed approach not only effectively preserves the details of different source images, but also excellently represents the irregular areas of the source images. On the other hand, a novel weighted average method based on bilateral filter is proposed to fuse low- and high-frequency subbands by taking advantage of spatial consistency of natural images. Experimental results demonstrate that the proposed method outperforms seven recently proposed image fusion methods in terms of both visual effect and objective evaluation metrics.

Molecular mapping of leaf rust resistance gene LrNJ97 in Chinese wheat line Neijiang 977671.

Neijiang 977671 and 19 near-isogenic lines with known leaf rust resistance genes were inoculated with 12 pathotypes of Puccinia triticina for postulation of leaf rust resistance genes effective at the seedling stage. The reaction pattern of Neijiang 977671 differed from those of the lines with known leaf rust resistance genes used in the test, indicating that Neijiang 977671 may carry a new leaf rust resistance gene(s). With the objective of identifying and mapping the new gene for resistance to leaf rust, F1 and F2 plants, and F2:3 families, from Neijiang 977671 × Zhengzhou 5389 (susceptible) were inoculated with Chinese P. triticina pathotype FHNQ in the greenhouse. Results from the F2 and F2:3 populations indicated that a single dominant gene, temporarily designated LrNJ97, conferred resistance. In order to identify other possible genes in Neijiang 977671 other eight P. triticina pathotypes avirulent on Neijiang 977671 were used to inoculate 25 F2:3 families. The results showed that at least three leaf rust resistance genes were deduced in Neijiang 977671. Bulked segregant analysis was performed on equal amounts of genomic DNA from 20 resistant and 20 susceptible F2 plants. SSR markers polymorphic between the resistant and susceptible bulks were used to analyze the F2:3 families. LrNJ97 was linked to five SSR loci on chromosome 2BL. The two closest flanking SSR loci were Xwmc317 and Xbarc159 at genetic distances of 4.2 and 2.2 cM, respectively. At present two designated genes (Lr50 and Lr58) are located on chromosome 2BL. In the seedling tests, the reaction pattern of LrNJ97 was different from that of Lr50. Lr50 and Lr58 were derived from T. armeniacum and Ae. triuncialis, respectively, whereas according to the pedigree of Neijiang 977671 LrNJ97 is from common wheat. Although seeds of lines with Lr58 were not available, it was concluded that LrNJ97 is likely to be a new leaf rust resistance gene.

Identifying the common elements of psychological and psychosocial interventions for preventing postpartum depression: Application of the distillation and matching model to 37 winning protocols from 36 intervention studies.

AIM: Postpartum depression is prevalent worldwide and seriously endangers maternal and child health. Previous studies have demonstrated the effectiveness of psychological and psychosocial intervention programmes in preventing postpartum depression. However, the literature offers limited practice guidance. Therefore, this study aimed to deeply analyse prior findings to gather rich evidence-based information on this topic. METHODS: Using the distillation and matching model, we conducted a systematic review of psychological and psychosocial interventions used to effectively prevent postpartum depression. Four researchers trained in coding system independently read eligible studies and identified reliable (Cohen's kappa >0.40) and frequently occurring (frequency ≥3 winning study groups) practice elements. RESULTS: Our review included 36 studies containing 37 winning study groups. Fourteen practice elements were identified and subsequently divided into six categories: postpartum practical problems-related, social support-related, interpersonal psychotherapy-related, cognitive behavioural therapy-related, labour trauma-related and non-specific techniques. The most common practice elements were baby care skills and mother-infant bonding/interaction enhancement. Inter-rater reliability averaged 0.86, ranging from 0.48 to 1. CONCLUSION: The practice elements identified in this study provide rich evidence-based information that can guide clinical practitioners in selecting or developing effective, realistically available intervention programmes.

NUF2 Expression Promotes Lung Adenocarcinoma Progression and Is Associated With Poor Prognosis.

Aberrant expression of the gene encoding the Ndc80 kinetochore complex component (NUF2) reportedly contributes to the progression of several human cancers. However, the functional roles of NUF2 and their underlying mechanisms in lung adenocarcinoma (LUAD) are largely unknown. The current study aimed to investigate the role of NUF2 in LUAD tumorigenesis. Here, TCGA, ONCOMINE, the Human Protein Atlas, UALCAN, and the results of our cohort were used to analyze the expression of NUF2 in LUAD. A Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were performed to estimate the prognostic values of NUF2 expression in the Cancer Genome Atlas cohort. We studied the effects of NUF2 expression on proliferation, migration, invasion, and tumor growth using LUAD cell lines. Gene set enrichment analysis (GSEA) was used to analyze the pathways and biological function enrichment of NUF2 in LUAD. The ssGSEA database was used to analyze the relationship between NUF2 expression and immune cell infiltration in LUAD. Results revealed elevated expression of NUF2 in LUAD specimens. Patients overexpressing NUF2 had poor prognoses relative to those with low NUF2 expression. Knockdown of NUF2 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition, and colony formation of LUAD cells. Moreover, NUF2 knockdown induced cell cycle arrest at the G0/G1 phase. Gene Ontology and GSEA analyses suggested that NUF2 may be involved in immunity, proliferation, and apoptosis-related pathways. NUF2 overexpression was positively correlated with differential immune cell infiltration. In conclusion, NUF2 expression was associated with the clinical phenotype of LUAD and hence has potential implications in LUAD treatment.

LncRNA RP3-326I13.1 promotes cisplatin resistance in lung adenocarcinoma by binding to HSP90B and upregulating MMP13.

Cisplatin (DDP) resistance has become the major obstacle in the therapy of malignant tumors, including lung adenocarcinoma (LAD). Long non-coding RNAs (lncRNAs) were confirmed to be related to DDP-resistance. Studies have shown that RP3-326I13.1 (also known as PINCR) could promote the progression of colorectal cancer, and RP3-326I13.1 knockdown could induce hypersensitivity to chemotherapy drugs. While the function of RP3-326I13.1 in LAD is unclear, therefore, this study aimed to research the biological function and related molecular mechanisms of RP3-326I13.1 in DDP-resistance of LAD. QPCR analysis found that RP3-326I13.1 was highly expressed in A549/DDP cells and LAD tissues. Cytological assays found that RP3-326I13.1 pro-moted the proliferation, migration, invasion, and DDP-resistance of LAD cell lines. Moreover, knock-down of RP3-326I13.1 could induce G1 phase arrest. Nude mouse xenograft assay confirmed that RP3-326I13.1 could promote tumor growth and DDP-resistance in vivo. Mechanically, RNA pull-down and mass spectrometry analysis indicated that heat shock protein HSP 90-beta (HSP90B) could be combined with RP3-326I13.1. HSP90B knockdown inhibited the effect of RP3-326I13.1 on proliferation, invasion, and promoted LAD cell lines apoptosis. Transcriptome sequencing analysis found that MMP13 was the downstream mRNA of RP3-326I13.1. In conclusion, RP3-326I13.1 could promote DDP-resistance of LAD by binding to HSP90B and upregulating human matrix metalloproteinase-13 (MMP-13) and may serve as a therapeutic target, as well as a biomarker for predicting DDP-resistance in LAD.Abbreviations:DDP: Cisplatin; LAD: Lung adenocarcinoma; LncRNAs: Long non-coding RNAs; qPCR: real-time fluorescent quantitative PCR; HSP90B: Heat shock protein HSP 90-beta; RPMI: Roswell Park Memorial Institute; FBS: Fetal bovine serum; CT: computed tomography; MRI: magnetic resonance imaging; RECIST: Response evaluation criteria in solid tumors; NC: Negative control; OE: overexpression; shRNA: short hairpin RNA; siRNA: small interfering RNA; CCK-8: Cell Counting Kit-8; IC50: The half maximal inhibitory concentration; PBS: Phosphate buffer saline; PI: propidium iodide; SDS-PAGE: sodiumdodecylsulfate-polyacrylamide gel electrophoresis; ceRNA: Competing endogenous RNA; HE: hematoxylin-eosin; ns: no significance.

ADH1C Facilitates Cisplatin Resistance of Lung Adenocarcinoma Cells.

Lung adenocarcinoma (LUAD) is a common form of lung cancer. Although cisplatin chemotherapy is an effective treatment option, some patients with LUAD can develop drug resistance. Modulated ADH1C expression has been reported in various cancer types. However, the mechanism by which ADH1C potentially influences progression and cisplatin resistance of LUAD remains poorly understood. In this study, we aimed to explore the role of ADH1C with respect to cisplatin resistance and to uncover the clinical significance of methionine adenosyltransferase (MAT1A). Compared with cisplatin-sensitive A549 cells, ADH1C was highly enriched in cisplatin-resistant A549/cis-dichlorodiammineplatinum II (DDP) cells. Inhibition of ADH1C expression in the latter suppressed cell proliferation and decreased their resistance to cisplatin. Furthermore, the proliferative capacity under cisplatin stimulation was reduced. Downregulation of ADH1C expression inhibited the expression of proliferating cell nuclear antigen and excision repair cross-complementing 1 (ERCC1). Knockdown of ADH1C resulted in arrested cell cycle (in G2/M phase). The proliferative capacity and cisplatin sensitivity induced by ADH1C upregulation in A549 cells were reversed upon knockdown of ADH1C. Bioinformatic analyses revealed ADH1C to be mainly enriched in cell cycle, RNA transport, biosynthesis of amino acids, and platinum drug resistance pathways. Meanwhile, the gene MAT1A with considerable positive association with ADH1C was identified. Furthermore, expression of MAT1A was upregulated in LUAD tissues relative to the paired adjacent normal specimens. Human Protein Atlas, The university of alabama at birmingham cancer data analysis portal (UALCAN), and Kaplan-Meier Plotter analysis indicated that upregulated MAT1A expression is correlated with poor prognosis of LUAD. Our results indicate that the ADH1C/MAT1A axis possibly increases cisplatin resistance in LUAD cells. The experiment was repeated three times and approved by the Medical Ethical Committee of the First Affiliated Hospital of Wenzhou Medical University (approval No.YS2018001).

CircRAPGEF5 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma through the miR-1236-3p/ZEB1 Axis and Serves as a Potential Biomarker.

Lung adenocarcinoma (LAD) is a common malignancy; however, its underlying molecular mechanism is unclear. Circular RNAs (circRNAs) serve as significant cancer regulators. The overexpression of circRAPGEF5 in LAD tissues and cells indicated that it may be involved in promoting LAD progression. Analysis of 61 LAD tissues revealed that circRAPGEF5 was related to lymph node metastasis. Functionally, circRAPGEF5 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition of LAD cells in vitro and promoted LAD cells growth in vivo. Mechanistically, dual-luciferase reporter assays confirmed direct interaction of circRAPGEF5, miR-1236-3p, and ZEB1. miR-1236-3p was upregulated and ZEB1 expression reduced after circRAPGEF5 knockdown, and the proliferation, migration, and invasion of LAD cells was inhibited. circRAPGEF5 was significantly overexpressed in LAD cell exosomes, and co-culture experiments showed that exosomal circRAPGEF5 enhanced the metastatic ability of LAD cells. Further experiments found that serum exosomal circRAPGEF5 was overexpressed in LAD; moreover, the area under the receiver operator characteristic curve of exosomal circRAPGEF5 was superior to that of serum carcinoembryonic antigen (CEA). Jointly detected serum exosomal circRAPGEF5 and serum CEA had better diagnostic performance than when detected individually. Thus, exosomal circRAPGEF5 could promote the proliferation and metastasis of LAD via the miR-1236-3p/ZEB1 axis and serum exosomal circRAPGEF5 may serve as a promising biomarker for LAD.