Basement membrane-related lncRNA signature for the prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the main type of primary liver cancer. This study aimed to develop a basement membrane (BM) related lncRNAs risk signature to evaluate the prognosis of HCC patients. We screened differentially expressed BM-related lncRNAs (DE-BMRlncRNAs) for risk evaluation, and identified six DE-BMRlncRNAs (AC072054.1, NUP50-DT, AC026412.3, AC109322.2, POLH-AS1 and LINC00595) for prognostic risk signature. HCC patients were divided to high or low risk according to median risk score. Our prognostic model predicted that patients with higher risk score had worse prognosis. We also created a nomogram to assist clinical decision-making according to risk score and clinicopathological features. Meanwhile, we confirmed the expression of six lncRNAs in HCC tissue and cells. POLH-AS1 knockdown inhibited the migration and invasion of HCC cells. In conclusion, we established a predictive model based on BMRlncRNAs to predict the prognosis of HCC. Our findings offer a rationale to further explore BM-related biomarkers for HCC.

Brazilin-7-2-butenoate inhibits amyloid ß-protein aggregation, alleviates cytotoxicity, and protects Caenorhabditis elegans.

The fibrillogenesis of amyloid ß-protein (Aß) gradually accumulates to form neurotoxic Aß aggregates in the human brain, which is the direct cause of Alzheimer's disease (AD) related symptoms. There are currently no effective therapies for AD. Brazilin, a natural polyphenol, inhibits Aß fibrillogenesis, disrupts the mature fibrils and alleviates the corresponding cytotoxicity, but it also has the high toxic. Therefore, brazilin-7-2-butenoate (B-7-2-B), a brazilin derivative, was designed and synthesized. B-7-2-B exhibited lower toxicity and stronger inhibitory effect on Aß aggregation than brazilin. B-7-2-B could prevent the formation of Aß fibrils and oligomers, and depolymerize pre-formed aggregates in a dose-dependent manner. Furthermore, B-7-2-B prominently alleviated the cytotoxicity and the oxidative stress induced by Aß aggregates in PC12 cells. The protective impacts of B-7-2-B were further demonstrated by using the Caenorhabditis elegans model, including decreasing the extent of Aß aggregation, improving the motility and sensation disorders. Eventually, B-7-2-B was proven to be no apparent damage to worms. In summarize, it can be concluded that B-7-2-B has the potential as a drug for treating AD.

Selenium Improves the Control Efficacy of Phytophthora nicotianae by Damaging the Cell Membrane System and Promoting Plant Energy Metabolism.

Tobacco black shank (TBS), caused by Phytophthora nicotianae, poses a significant threat to tobacco plants. Selenium (Se), recognized as a beneficial trace element for plant growth, exhibited inhibitory effects on P. nicotianae proliferation, disrupting the cell membrane integrity. This action reduced the energy supply and hindered hyphal transport through membrane proteins, ultimately inducing hyphal apoptosis. Application of 8 mg/L Se through leaf spraying resulted in a notable decrease in TBS incidence. Moreover, Se treatment preserved chloroplast structure, elevated chitinase activities, ß-1,3-GA, polyphenol oxidase, phenylalanine ammonia-lyase, and increased hormonal content. Furthermore, Se enhanced flavonoid and sugar alcohol metabolite levels while diminishing amino acid and organic acid content. This shift promoted amino acid degradation and flavonoid synthesis. These findings underscore the potential efficacy of Se in safeguarding tobacco and potentially other plants against P. nicotianae.

Selenium-molybdenum interactions reduce chromium toxicity in Nicotiana tabacum L. by promoting chromium chelation on the cell wall.

Chromium (Cr) is a hazardous heavy metal that negatively affects animals and plants. The micronutrients selenium (Se) and molybdenum (Mo) have been widely shown to alleviate heavy metal toxicity in plants. However, the molecular mechanism of Cr chelation on the cell wall by combined treatment with Se and Mo has not been reported. Therefore, this study aimed to explore the effects of Se-Mo interactions on the subcellular distribution of Cr (50 µM) and on cell wall composition, structure, functional groups and Cr content, in addition to performing a comprehensive analysis of the transcriptome. Our results showed that the cell walls of shoots and roots accumulated 51.0% and 65.0% of the Cr, respectively. Furthermore, pectin in the cell wall bound 69.5%/90.2% of the Cr in the shoots/roots. Se-Mo interactions upregulated the expression levels of related genes encoding galacturonosyltransferase (GAUT), UTP-glucose-1-phosphate uridylyltransferase (UGP), and UDP-glucose-4-epimerase (GALE), involved in polysaccharide biosynthesis, thereby increasing pectin and cellulose levels. Moreover, combined treatment with Se and Mo increased the lignin content and cell wall thickness by upregulating the expression levels of genes encoding cinnamyl alcohol dehydrogenase (CAD), peroxidase (POX) and phenylalanine amino-lyase (PAL), involved in lignin biosynthesis. Fourier-transform infrared (FTIR) spectroscopy results showed that Se + Mo treatment (in combination) increased the number of carboxylic acid groups (-COOH) groups, thereby enhancing the Cr chelation ability. The results not only elucidate the molecular mechanism of action of Se-Mo interactions in mitigating Cr toxicity but also provide new insights for phytoremediation and food safety.

Capturing the multifaceted function of adipose tissue macrophages.

Adipose tissue macrophages (ATMs) bolster obesity-induced metabolic dysfunction and represent a targetable population to lessen obesity-associated health risks. However, ATMs also facilitate adipose tissue function through multiple actions, including adipocyte clearance, lipid scavenging and metabolism, extracellular remodeling, and supporting angiogenesis and adipogenesis. Thus, high-resolution methods are needed to capture macrophages' dynamic and multifaceted functions in adipose tissue. Herein, we review current knowledge on regulatory networks critical to macrophage plasticity and their multifaceted response in the complex adipose tissue microenvironment.

Performance of 18F-DCFPyL PET/CT in Primary Prostate Cancer Diagnosis, Gleason Grading and D'Amico Classification: A Radiomics-Based Study.

This study aimed to investigate the performance of 18F-DCFPyL positron emission tomography/computerized tomography (PET/CT) models for predicting benign-vs-malignancy, high pathological grade (Gleason score > 7), and clinical D'Amico classification with machine learning. The study included 138 patients with treatment-naïve prostate cancer presenting positive 18F-DCFPyL scans. The primary lesions were delineated on PET images, followed by the extraction of tumor-to-background-based general and higher-order textural features by applying five different binning approaches. Three layer-machine learning approaches were used to identify relevant in vivo features and patient characteristics and their relative weights for predicting high-risk malignant disease. The weighted features were integrated and implemented to establish individual predictive models for malignancy (Mm), high path-risk lesions (by Gleason score) (Mgs), and high clinical risk disease (by amico) (Mamico). The established models were validated in a Monte Carlo cross-validation scheme. In patients with all primary prostate cancer, the highest areas under the curve for our models were calculated. The performance of established models as revealed by the Monte Carlo cross-validation presenting as the area under the receiver operator characteristic curve (AUC): 0.97 for Mm, AUC: 0.73 for Mgs, AUC: 0.82 for Mamico. Our study demonstrated the clinical potential of 18F-DCFPyL PET/CT radiomics in distinguishing malignant from benign prostate tumors, and high-risk tumors, without biopsy sampling. And in vivo 18F-DCFPyL PET/CT can be considered a noninvasive tool for virtual biopsy for personalized treatment management. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00108-y.

Selenium and molybdenum synergistically alleviate chromium toxicity by modulating Cr uptake and subcellular distribution in Nicotiana tabacum L.

Chromium (Cr) is a harmful heavy metal that poses a serious threat to plants and animals. Selenium (Se) and molybdenum (Mo) are two beneficial elements for plant growth and resistance. However, their interactive effects on Cr uptake and distribution are poorly understood. Therefore, a hydroponics experiment was conducted to explore the effects of the use of Se and Mo alone and simultaneously on mitigating Cr toxicity. In this study, Nicotiana tabacum L. seedlings were exposed to control, 50 µM Cr, 50 µM Cr + 2 µM Se, 50 µM Cr + 1 µM Mo, or 50 µM Cr + 2 µM Se + 1 µM Mo in Hoagland solution. After 2 weeks, the plant biomass, Cr, Se and Mo contents, photosynthesis, leaf ultrastructure, antioxidant system, subcellular distribution and associated gene expression in Nicotiana tabacum L. were determined. The results showed that simultaneous use of Se and Mo promoted tobacco growth under Cr stress, as evidenced by reducing reactive oxygen species (ROS) content and reducing Cr translocation factor (TF) and inducing a 51.3% reduction in Cr content in shoots. Additionally, Se-Mo interactions increased the levels of glutathione (GSH) and phytochelatin (PC) and the distribution of Cr in the cell walls and organelles. Furthermore, the relative expression of PCS1 was upregulated, while those of NtST1 and MSN1 were downregulated. The results concluded that the simultaneous use of Se and Mo effectively alleviated Cr toxicity in Nicotiana tabacum L., which not only offers an efficient way for crops to resist Cr toxicity but also provides evidence for the benefit of Se combined with Mo.

Macrophages at the Crossroad of Meta-Inflammation and Inflammaging.

Macrophages are central players in systemic inflammation associated with obesity and aging, termed meta-inflammation and inflammaging. Activities of macrophages elicited by the two chronic conditions display shared and distinct patterns mechanistically, resulting in multifaceted actions for their pathogenic roles. Drastically expanded tissue macrophage populations under obesity and aging stress attribute to both enhanced recruitment and local expansion. Importantly, molecular networks governing the multifaceted actions of macrophages are directly altered by environmental cues and subsequently contribute to metabolic reprogramming, resulting in meta-inflammation in obesity or inflammaging in aging. In this review, we will summarize how meta-inflammation and inflammaging affect macrophages and the molecular mechanisms involved in these processes.

Correlation of miRNA-21 and blood Cr levels with tumor infiltration and distant metastasis in renal cancer patients.

The object of this study was to explore the correlation analysis between miRNA-21 and blood Cr levels with tumor invasion and distant metastasis in renal cancer patients. For this purpose 49 cases of renal cancer patients treated in our hospital from February 2018 to March 2020 were selected as the study group, and another 165 cases of renal benign tumors that were pathologically confirmed in our hospital during the same period were selected as the control group. MiRNA-21 and blood Cr levels, miRNA-21 and blood Cr levels at different stages, and miRNA-21 and blood Cr levels when tumor invasion and distant metastasis were present were compared between the two groups. Results showed that compared with the control group, the levels of miRNA-21 and blood Cr in the study group increased, the difference was significant (P < 0. 05); compared with stage I patients, the levels of miRNA-21 and blood Cr in stage II patients increased, compared with stage II patients, the levels of miRNA-21 and blood Cr in stage III patients increased, compared with stage III patients, the levels of miRNA-21 and blood Cr in stage IV patients increased, the difference was significant Compared with the case without tumor invasion, the levels of miRNA-21 and blood Cr in the case of tumor invasion were increased, the difference was statistically significant (P < 0. 05); compared with the case without distant metastasis, the levels of miRNA-21 and blood Cr in the case of tumor distant metastasis were increased, the difference was significant (P < 0. 05) When distant metastasis, miRNA-21 and blood Cr levels increased significantly, which showed that miRNA-21 and blood Cr levels were positively correlated with tumor invasion and distant metastasis; compared with the control group, TIMP1, TIMP2, MACC1 protein expression in the study group increased, and the three showed a positive correlation, the difference was significant (P < 0. 05). It is concluded when renal cancer patients were tested, we found that miRNA-21 and blood Cr levels were abnormally increased, and the two had a certain correlation with renal cancer tumor invasion and distant metastasis, which showed a positive correlation.

Brown-fat-mediated tumour suppression by cold-altered global metabolism.

Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues1-6. Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis2,7,8. Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes4,5,9. However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1-the key mediator for BAT-thermogenesis-ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers.

Lysosomal K+ channel TMEM175 promotes apoptosis and aggravates symptoms of Parkinson's disease.

Lysosomes are degradative organelles and play vital roles in a variety of cellular processes. Ion channels on the lysosomal membrane are key regulators of lysosomal function. TMEM175 has been identified as a lysosomal potassium channel, but its modulation and physiological functions remain unclear. Here, we show that the apoptotic regulator Bcl-2 binds to and inhibits TMEM175 activity. Accordingly, Bcl-2 inhibitors activate the channel in a caspase-independent way. Increased TMEM175 function inhibits mitophagy, disrupts mitochondrial homeostasis, and increases production of reactive oxygen species (ROS). ROS further activates TMEM175 and thus forms a positive feedback loop to augment apoptosis. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD), knockout (KO) of TMEM175 mitigated motor impairment and dopaminergic (DA) neuron loss, suggesting that TMEM175-mediated apoptosis plays an important role in Parkinson's disease (PD). Overall, our study reveals that TMEM175 is an important regulatory site in the apoptotic signaling pathway and a potential therapeutic target for Parkinson's disease (PD).

NtRAV4 negatively regulates drought tolerance in Nicotiana tabacum by enhancing antioxidant capacity and defence system.

KEY MESSAGE: NtRAV4 is a nucleus-localised protein and no self-activation effect. ntrav4 mutants maintain the steady state of the ROS system under drought stress by enhancing antioxidant capacity and defence system. The APETALA2/ethylene response factor (AP2/ERF) transcription factor (TF) family plays an important role in plant responses to environmental stresses. In this study, we identified a novel NtRAV4 TF, a member of RAV subfamily among AP2/ERF gene family, which have AP2 and B3 domain in its N- and C-terminus, respectively. Subcellular localisation and self-activation activity analysis revealed that NtRAV4 localised in the nucleus and had no self-activation effect. The overexpression and gene editing vectors of NtRAV4 were constructed by homologous recombination and CRISPR/Cas9 gene editing methods, and transformed into tobacco by agrobacterium-mediated method. ntrav4 led to the appearance of termination codon in advance and lacked the unique B3 domain of RAV subfamily protein. Further analysis displayed that knockout of the NtRAV4 in tobacco increased drought tolerance with high relative water content, accompanied by reduced stomatal aperture, density, and stomatal opening ratio compared to overexpression lines and WT. Moreover, ntrav4 knockout plants also exhibited increased osmotic tolerance with low malondialdehyde (MDA) and ion leakage (EL), less accumulation of O2•- and H2O2, and high enzymatic antioxidant (SOD, POD, CAT) activities, non-enzymatic antioxidant (AsA-GSH cycle) contents and hormone (IAA, ABA, GA3, and ZR) levels under drought stress. Furthermore, ntrav4 mutants in tobacco improved the expression levels of ROS-related proline synthesis and stress-responsive genes under osmotic stress. Our results indicate that NtRAV4 negatively regulates plant tolerance to drought stress by reducing water loss and activating the antioxidant system and stress-related gene expression to maintain the steady state of the ROS system.

A novel strategy to dissect multifaceted macrophage function in human diseases.

Macrophages are widely distributed immune cells that play central roles in a variety of physiologic and pathologic processes, including obesity and cardiovascular disease (CVD). They are highly plastic cells that execute diverse functions according to a combination of signaling and environmental cues. While macrophages have traditionally been understood to polarize to either proinflammatory M1-like or anti-inflammatory M2-like states, evidence has shown that they exist in a spectrum of states between those 2 phenotypic extremes. In obesity-related disease, M1-like macrophages exacerbate inflammation and promote insulin resistance, while M2-like macrophages reduce inflammation, promoting insulin sensitivity. However, polarization markers are expressed inconsistently in adipose tissue macrophages, and they additionally exhibit phenotypes differing from the M1/M2 paradigm. In atherosclerotic CVD, activated plaque macrophages can also exist in a range of proinflammatory or anti-inflammatory states. Some of these macrophages scavenge lipids, developing into heterogeneous foam cell populations. To better characterize the many actions of macrophages in human disease, we have designed a novel set of computational tools: MacSpectrum and AtheroSpectrum. These tools provide information on the inflammatory polarization status, differentiation, and foaming of macrophages in both human and mouse samples, allowing for better characterization of macrophage subpopulations based on their function. Using these tools, we identified disease-relevant cell states in obesity and CVD, including the novel concept that macrophage-derived foam cell formation can follow homeostatic noninflammatory or pathogenic inflammatory foaming programs.

Impact of microRNA Regulated Macrophage Actions on Adipose Tissue Function in Obesity.

Obesity-induced adipose tissue dysfunction is bolstered by chronic, low-grade inflammation and impairs systemic metabolic health. Adipose tissue macrophages (ATMs) perpetuate local inflammation but are crucial to adipose tissue homeostasis, exerting heterogeneous, niche-specific functions. Diversified macrophage actions are shaped through finely regulated factors, including microRNAs, which post-transcriptionally alter macrophage activation. Numerous studies have highlighted microRNAs' importance to immune function and potential as inflammation-modulatory. This review summarizes current knowledge of regulatory networks governed by microRNAs in ATMs in white adipose tissue under obesity stress.

Clinical Potential of lncRNA PPP1R26-AS1 in Breast Cancer and Its Contribution to Cancer Progression.

Breast cancer has become the most leading diagnosed tumor worldwide in 2020. In this study, the biomarker potential and influence on the cellular function of lncRNA PPP1R26-AS1 was investigated in breast cancer. Expression levels of lncRNA PPP1R26-AS1 in breast tissues and cells were detected by RT-qPCR. Association between lncRNA PPP1R26-AS1 level and clinical parameters was investigated by Chi-square analysis. The prognostic potential was assessed by Kaplan-Meier and multivariate Cox regression analysis. Knockdown of lncRNA PPP1R26-AS1 was subjected to study the effect on cell proliferation, invasion, and migration by CCK-8 and transwell assay. The bind between PPP1R26-AS1 and miR-1226-3p was investigated. LncRNA PPP1R26-AS1 was highly expressed in breast tissues and cell lines. This upregulation was correlated with pTNM, positive ER status, luminal B subtype, positive nodal status, and shorter overall survival in breast cancer patients. Significant decreases in proliferation, migration, and invasion activity were observed upon knockdown of lncRNA PPP1R26-AS1. lncRNA PPP1R26-AS1 could act as ceRNA to bind with miR-1226-3p in breast cancer. LncRNA PPP1R26-AS1, as oncogenic lncRNA, could provide a new perspective on the development of prognostic biomarkers and a new approach in tailoring the treatment personalized in breast cancer.

A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients.

Immune checkpoint inhibitor (ICI) therapy continues to revolutionize melanoma treatment, but only a subset of patients respond. Major efforts are underway to develop minimally invasive predictive assays of ICI response. Using single-cell transcriptomics, we discovered a unique CD8 T cell blood/tumor-shared subpopulation in melanoma patients with high levels of oxidative phosphorylation (OXPHOS), the ectonucleotidases CD38 and CD39, and both exhaustion and cytotoxicity markers. We called this population with high levels of OXPHOS "CD8+ TOXPHOS cells." We validated that higher levels of OXPHOS in tumor- and peripheral blood-derived CD8+ TOXPHOS cells correlated with ICI resistance in melanoma patients. We then developed an ICI therapy response predictive model using a transcriptomic profile of CD8+ TOXPHOS cells. This model is capable of discerning responders from nonresponders using either tumor or peripheral blood CD8 T cells with high accuracy in multiple validation cohorts. In sum, CD8+ TOXPHOS cells represent a critical immune population to assess ICI response with the potential to be a new target to improve outcomes in melanoma patients.

AtheroSpectrum Reveals Novel Macrophage Foam Cell Gene Signatures Associated With Atherosclerotic Cardiovascular Disease Risk.

BACKGROUND: Whereas several interventions can effectively lower lipid levels in people at risk for atherosclerotic cardiovascular disease (ASCVD), cardiovascular event risks remain, suggesting an unmet medical need to identify factors contributing to cardiovascular event risk. Monocytes and macrophages play central roles in atherosclerosis, but studies have yet to provide a detailed view of macrophage populations involved in increased ASCVD risk. METHODS: A novel macrophage foaming analytics tool, AtheroSpectrum, was developed using 2 quantitative indices depicting lipid metabolism and the inflammatory status of macrophages. A machine learning algorithm was developed to analyze gene expression patterns in the peripheral monocyte transcriptome of MESA participants (Multi-Ethnic Study of Atherosclerosis; set 1; n=911). A list of 30 genes was generated and integrated with traditional risk factors to create an ASCVD risk prediction model (30-gene cardiovascular disease risk score [CR-30]), which was subsequently validated in the remaining MESA participants (set 2; n=228); performance of CR-30 was also tested in 2 independent human atherosclerotic tissue transcriptome data sets (GTEx [Genotype-Tissue Expression] and GSE43292). RESULTS: Using single-cell transcriptomic profiles (GSE97310, GSE116240, GSE97941, and FR-FCM-Z23S), AtheroSpectrum detected 2 distinct programs in plaque macrophages-homeostatic foaming and inflammatory pathogenic foaming-the latter of which was positively associated with severity of atherosclerosis in multiple studies. A pool of 2209 pathogenic foaming genes was extracted and screened to select a subset of 30 genes correlated with cardiovascular event in MESA set 1. A cardiovascular disease risk score model (CR-30) was then developed by incorporating this gene set with traditional variables sensitive to cardiovascular event in MESA set 1 after cross-validation generalizability analysis. The performance of CR-30 was then tested in MESA set 2 (P=2.60×10-4; area under the receiver operating characteristic curve, 0.742) and 2 independent data sets (GTEx: P=7.32×10-17; area under the receiver operating characteristic curve, 0.664; GSE43292: P=7.04×10-2; area under the receiver operating characteristic curve, 0.633). Model sensitivity tests confirmed the contribution of the 30-gene panel to the prediction model (likelihood ratio test; df=31, P=0.03). CONCLUSIONS: Our novel computational program (AtheroSpectrum) identified a specific gene expression profile associated with inflammatory macrophage foam cells. A subset of 30 genes expressed in circulating monocytes jointly contributed to prediction of symptomatic atherosclerotic vascular disease. Incorporating a pathogenic foaming gene set with known risk factors can significantly strengthen the power to predict ASCVD risk. Our programs may facilitate both mechanistic investigations and development of therapeutic and prognostic strategies for ASCVD risk.

Metabolomic profiling of single enlarged lysosomes.

Lysosomes are critical for cellular metabolism and are heterogeneously involved in various cellular processes. The ability to measure lysosomal metabolic heterogeneity is essential for understanding their physiological roles. We therefore built a single-lysosome mass spectrometry (SLMS) platform integrating lysosomal patch-clamp recording and induced nano-electrospray ionization (nanoESI)/mass spectrometry (MS) that enables concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes. The accuracy and reliability of this technique were validated by supporting previous findings, such as the transportability of lysosomal cationic amino acids transporters such as PQLC2 and the lysosomal trapping of lysosomotropic, hydrophobic weak base drugs such as lidocaine. We derived metabolites from single lysosomes in various cell types and classified lysosomes into five major subpopulations based on their chemical and biological divergence. Senescence and carcinoma altered metabolic profiles of lysosomes in a type-specific manner. Thus, SLMS can open more avenues for investigating heterogeneous lysosomal metabolic changes during physiological and pathological processes.

LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1 axis.

BACKGROUND: Long intergenic non-protein coding RNA 00342 (LINC00342) has been identified as a novel oncogene. However, the functional role of LINC00342 in colorectal cancer (CRC) remains unclear. METHODS: The expression of LINC00342 is detected by real-time PCR (RT-PCR) analysis. Cell proliferation, migration and invasion and xenograft model are examined to analyze the biological functions of LINC00342 in vitro and in vivo using colony formation, would healing and transwell analyses. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays are used to identify the target interactions between LINC00342, miR-19a-3p and aminopeptidase like 1 (NPEPL1). RESULTS: LINC00342 was highly expressed in CRC. Down-regulation of LINC00342 inhibited cell proliferation and metastasis of CRC cells. Moreover, knocking down LINC00342 inhibited the tumor growth in vivo. Mechanistic investigation revealed that LINC00342 might sponge miR-19a-3p to regulate NPEPL1 expression. Further investigation indicated that the ontogenesis facilitated by LINC00342 was inhibited due to the depletion of NPEPL1. CONCLUSION: LINC00342 promotes CRC progression by competitively binding miR-19a-3p with NPEPL1.

Value of 18F-FDG PET/CT in patients with hepatic metastatic carcinoma of unknown primary.

PURPOSE: This retrospective study aimed to investigate the clinical value of -deoxy-2-(F)-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in detecting primary lesions of hepatic metastases. METHODS: A total of 124 patients with hepatic metastatic carcinoma of unknown primary underwent whole body F-FDG PET/CT imaging. According to the final diagnoses for both primary sites and hepatic metastases that were confirmed either histopathologically or by clinical follow up, all patients were divided into 4 groups: a true positive group (TP, 95 cases), a false positive group (FP, 9), a true negative group (TN, 8) and a false negative group (FN, 12). RESULTS: The TP rate of primary lesions, detected by F-FDG PET/CT, was 76.61%, the FP rate 7.26%, the TN rate 6.45% and the FN rate 9.68%. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of F-FDG PET/CT in the detection of primary tumors were 88.78%, 52.94%, 91.35%, 40%, and 83.06%, respectively. Accurate diagnosis groups (TP, TN) showed a significantly higher SUVmax (standard uptake maximum value) level than that in error diagnosis groups (FP, FN). The SUVmax between hepatic metastases and primary lesions had a positive correlation. The primary tumor sites of hepatic metastases were mainly located in the gastrointestinal organs and the lungs. CONCLUSIONS: Whole body F-FDG PET/CT imaging was sensitive for detecting primary sites/lesions with hepatic metastatases of unknown primary, especially when the SUVmax of hepatic metastases were greater than 4.7.