Long non-coding RNAFOXD1-AS1 modulated CTCs epithelial-mesenchymal transition and immune escape in hepatocellular carcinoma in vitro by sponging miR-615-3p.

BACKGROUND: Hepatocellular carcinoma (HCC) is widely recognized as a globally prevalent malignancy. Immunotherapy is a promising therapy for HCC patients. Increasing evidence suggests that lncRNAs are involved in HCC progression and immunotherapy. AIM: The study reveals the mechanistic role of long non-coding RNA (lncRNA) FOXD1-AS1 in regulating migration, invasion, circulating tumor cells (CTCs), epithelial-mesenchymal transition (EMT), and immune escape in HCC in vitro. METHODS: This study employed real-time PCR (RT-qPCR) to measure FOXD1-AS1, miR-615-3p, and programmed death-ligand 1 (PD-L1). The interactions of FOXD1-AS1, miR-615-3p, and PD-L1 were validated via dual-luciferase reporter gene and ribonucleoprotein immunoprecipitation (RIP) assay. In vivo experimentation involves BALB/c mice and BALB/c nude mice to investigate the impact of HCC metastasis. RESULTS: The upregulation of lncRNA FOXD1-AS1 in malignant tissues significantly correlates with poor prognosis. The investigation was implemented on the impact of lncRNA FOXD1-AS1 on the migratory, invasive, and EMT of HCC cells. It has been observed that the lncRNA FOXD1-AS1 significantly influences the generation and metastasis of MCTC in vivo analysis. In mechanistic analysis, lncRNA FOXD1-AS1 enhanced immune escape in HCC via upregulation of PD-L1, which acted as a ceRNA by sequestering miR-615-3p. Additionally, lncRNA FOXD1-AS1 was found to modulate the EMT of CTCs through the activation of the PI3K/AKT pathway. CONCLUSION: This study presents compelling evidence supporting the role of lncRNA FOXD1-AS1 as a miRNA sponge that sequesters miR-655-3p and protects PD-L1 from suppression.

Uptake, tissue distribution, and biotransformation pattern of triclosan in tilapia exposed to environmentally-relevant concentrations.

Although triclosan has been ubiquitously detected in aquatic environment and is known to have various adverse effects to fish, details on its uptake, bioconcentration, and elimination in fish tissues are still limited. This study investigated the uptake and elimination toxicokinetics, bioconcentration, and biotransformation potential of triclosan in Nile tilapia (Oreochromis niloticus) exposed to environmentally-relevant concentrations under semi-static regimes for 7 days. For toxicokinetics, triclosan reached a plateau concentration within 5-days of exposure, and decreased to stable concentration within 5 days of elimination. Approximately 50 % of triclosan was excreted by fish through feces, and up to 29 % of triclosan was excreted through the biliary excretion. For fish exposed to 200 ng·L-1, 2000 ng·L-1, and 20,000 ng·L-1, the bioconcentration factors (log BCFs) of triclosan in fish tissues obeyed similar order: bile ≈ intestine > gonad ≈ stomach > liver > kidney ≈ gill > skin ≈ plasma > brain > muscle. The log BCFs of triclosan in fish tissues are approximately maintained constants, no matter what triclosan concentrations in exposure water. Seven biotransformation products of triclosan, involved in both phase I and phase II metabolism, were identified in this study, which were produced through hydroxylation, bond cleavages, dichlorination, and sulfation pathways. Metabolite of triclosan-O-sulfate was detected in all tissues of tilapia, and more toxic product of 2,4-dichlorophenol was also found in intestine, gonad, and bile of tilapia. Meanwhile, two metabolites of 2,4-dichlorophenol-O-sulfate and monohydroxy-triclosan-O-sulfate were firstly discovered in the skin, liver, gill, intestine, gonad, and bile of tilapia in this study. These findings highlight the importance of considering triclosan biotransformation products in ecological assessment. They also provide a scientific basis for health risk evaluation of triclosan to humans, who are associated with dietary exposure through ingesting fish.

N6-methyladenosine of TRIM27 enhances the stem cell-type phenotype of cisplatin-resistant colorectal cancer cells.

Colorectal cancer (CRC), classified as a lethal form of cancer, substantially threatens human well-being. Cancer stem cells (CSCs) reflect subsets for cancerous cells having basic stem-cell type properties, being significantly involved in the development of chemoresistance and tumor relapsing. The aberrant TRIM27 expression in various types of cancer indicates its potential involvement in cancer growth and progression. The current understanding of the TRIM27 involvement in CRC remains limited. In current study indicated that TRIM27 can potentially promote CSC-type phenotype of Cisplatin (DDP)-resistant CRC cells. YTHDF1 recruitment onto m6A-amended TRIM27 was crucial for facilitating the TRIM27 translating process in DDP-resistant CRC cells. The present research proposes that TRIM27 exhibits an oncogenic role by enhancing the CSC-type properties in DDP-resistant CRC via the m6A-modified pathway. The potential therapy for combating the relapse of CRC may include TRIM27 and YTHDF1, as they have been found to have significant roles in promoting CSC-type phenotypic characteristics.

Dynamic circulating tumor DNA during chemoradiotherapy predicts clinical outcomes for locally advanced non-small cell lung cancer patients.

The value of circulating tumor DNA (ctDNA) during chemoradiotherapy (CRT) remains unclear but is critical for detecting molecular residual disease (MRD). In this prospective study, we sequenced 761 blood samples from 139 patients with locally advanced non-small cell lung cancer treated with definitive radiation therapy (RT). ctDNA concentrations showed a significantly declining trend as CRT progressed at on-RT and after-RT time points versus baseline. Thirty-eight (27.3%) patients with early undetectable ctDNA at both on-RT (RT reached 40 Gy) and after-RT time points, indicating early response to CRT, had better survival outcomes for both with or without consolidation immune checkpoint inhibitors. Longitudinal undetectable MRD was found in 20.1% patients. The 2-year cancer-specific progression-free survival of these patients was 88.4%, corresponding to a potentially cured population. Further analysis revealed that pretreatment ctDNA variants serve as an essential MRD informed source. These data provide clinical insights for ctDNA-MRD detection.

Efficacy evaluation of neoadjuvant immunotherapy plus chemotherapy for non-small-cell lung cancer: comparison of PET/CT with postoperative pathology.

OBJECTIVES: To assess the value of positron emission tomography/computed tomography (PET/CT) in the efficacy evaluation of patients undergoing neoadjuvant immunotherapy plus chemotherapy, and to analyze its correlation with postoperative pathology. METHODS: The PET/CT metabolic parameters and CT size were retrospectively analyzed before and after neoadjuvant immunotherapy plus chemotherapy in 67 patients with resectable stage II/IIIA non-small-cell lung cancer (NSCLC). CT assessment based on immune response evaluation criteria in solid tumor criteria ((i)RECIST) was compared with PET/CT assessment based on the response criteria in solid tumors (PERCIST). The correlations between PET/CT metabolic parameters and postoperative pathology were analyzed. The value of PET/CT in the efficacy evaluation was assessed. RESULTS: The PET/CT assessment showed high consistency with postoperative pathological evaluation, yet the CT assessment showed low consistency with postoperative pathological evaluation. The (i)RECIST and PERCIST criteria showed statistically significant differences (p < 0.001). The postoperative pathological response was negatively associated with ΔSUVmax (%) (r = - 0.812, p < 0.001), ΔSUVmean (%) (r = - 0.805, p < 0.001), and ΔSUVpeak (%) (r = - 0.800, p < 0.001). The cut-off values of 75.8 for ΔSUVmax (%), 67.8 for ΔSUVmean (%), and 74.6 for ΔSUVpeak (%) had the highest sensitivity and specificity. CONCLUSION: The PERCIST criteria are more sensitive and accurate than (i)RECIST criteria to identify more responders when evaluating the response of neoadjuvant immunotherapy plus chemotherapy for NSCLC. PET/CT shows high accuracy in predicting postoperative pathological response. Our study shows the important role PET/CT plays in the efficacy evaluation of NSCLC patients undergoing neoadjuvant immunotherapy plus chemotherapy, as well as in predicting the prognosis and guiding postoperative treatment. CLINICAL RELEVANCE STATEMENT: Neoadjuvant immunotherapy plus chemotherapy is highly effective in the treatment of non-small-cell lung cancer. And PET/CT played an important role in the efficacy evaluation following neoadjuvant immunotherapy plus chemotherapy for non-small-cell lung cancer. KEY POINTS: • Neoadjuvant immunotherapy plus chemotherapy is highly effective in the treatment of NSCLC. • The PERCIST criteria are more sensitive and accurate than (i)RECIST criteria to identify more responders when evaluating the response of neoadjuvant immunotherapy plus chemotherapy for NSCLC. • PET/CT played an important role in the efficacy evaluation; ΔSUVmax (%), ΔSUVmean (%), and ΔSUVpeak (%) following neoadjuvant immunotherapy plus chemotherapy for NSCLC had high consistency and strong correlations with postoperative pathology.

[Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels].

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

Detection and Classification of Cotton Foreign Fibers Based on Polarization Imaging and Improved YOLOv5.

It is important to detect and classify foreign fibers in cotton, especially white and transparent foreign fibers, to produce subsequent yarn and textile quality. There are some problems in the actual cotton foreign fiber removing process, such as some foreign fibers missing inspection, low recognition accuracy of small foreign fibers, and low detection speed. A polarization imaging device of cotton foreign fiber was constructed based on the difference in optical properties and polarization characteristics between cotton fibers. An object detection and classification algorithm based on an improved YOLOv5 was proposed to achieve small foreign fiber recognition and classification. The methods were as follows: (1) The lightweight network Shufflenetv2 with the Hard-Swish activation function was used as the backbone feature extraction network to improve the detection speed and reduce the model volume. (2) The PANet network connection of YOLOv5 was modified to obtain a fine-grained feature map to improve the detection accuracy for small targets. (3) A CA attention module was added to the YOLOv5 network to increase the weight of the useful features while suppressing the weight of invalid features to improve the detection accuracy of foreign fiber targets. Moreover, we conducted ablation experiments on the improved strategy. The model volume, mAP@0.5, mAP@0.5:0.95, and FPS of the improved YOLOv5 were up to 0.75 MB, 96.9%, 59.9%, and 385 f/s, respectively, compared to YOLOv5, and the improved YOLOv5 increased by 1.03%, 7.13%, and 126.47%, respectively, which proves that the method can be applied to the vision system of an actual production line for cotton foreign fiber detection.

Crosstalk of renal cell carcinoma cells and tumor-associated macrophages aggravates tumor progression by modulating muscleblind-like protein 2/B-cell lymphoma 2/beclin 1-mediated autophagy.

BACKGROUND AIMS: M2-polarized tumor-associated macrophages contribute to the development of multiple human cancers, including renal cell carcinoma (RCC). However, the crosstalk mechanism between M2 macrophages and RCC remains unclear. METHODS: The authors constructed a co-culture system of M2 macrophages differentiated from THP-1 and RCC cells. Microscopic examination and quantitative real­time polymerase chain reaction (qRT-PCR) validated the morphology and types of macrophages. The proliferation, migration and invasion of RCC cells were assessed by Cell Counting Kit 8 (Dojindo Molecular Technologies, Inc, Santa Clara, CA, USA) and Transwell assay (Corning, Corning, NY, USA). Messenger RNA (mRNA) and protein expression of target molecules was detected by qRT­PCR and western blotting. Expression of Ki-67, E-cadherin and N-cadherin was measured by immunofluorescence staining or immunohistochemistry. Molecular interaction was evaluated by RNA pull-down, RNA immunoprecipitation and co-immunoprecipitation. A xenograft model was established to determine tumor growth in vivo. RESULTS: RCC cells triggered the activation of M2 macrophages. Functionally, M2-polarized macrophages facilitated the growth, migration, invasion and epithelial-mesenchymal transition of RCC cells by suppressing autophagy, whereas rapamycin, an activator of autophagy, significantly counteracted the tumor-promoting effects of M2 macrophages. Mechanistically, M2 macrophage-derived C-C motif chemokine 2 (CCL2) enhanced modulation of muscleblind-like protein 2 (MBNL2) expression. MBNL2 raised the stability of B-cell lymphoma 2 (Bcl-2) by directly binding to Bcl-2 mRNA, which endowed RCC cells with malignant properties via inhibition of beclin 1-dependent autophagy. CONCLUSIONS: RCC-induced M2-polarized macrophages secrete CCL2 to promote the growth and metastasis of RCC cells via inhibition of MBNL2/Bcl-2/beclin 1-mediated autophagy, which provide a novel perspective for the development of a therapeutic strategy for -RCC.

Investigation on the incidence and risk factors of lung cancer among Chinese hospital employees.

OBJECTIVE: In recent years, the lung cancer incidence has grown and the population is younger. We intend to find out the true detection rate of pulmonary nodules and the incidence of lung cancer in the population and search for the risk factors. METHOD: Hospital employees ≥40 years old who underwent low-dose computed tomography (CT) lung cancer screening from January 2019 to March 2022 were selected to record CT-imaging characteristics, pathology, staging, and questionnaires to investigate past history, smoking history, diet, mental health, etc. PM2.5 and radiation intake in radiation-related occupation received monitoring in hospital. RESULT: The detection rate of suspicious pulmonary nodules was 9.1% (233/2552), and the incidence rate of lung cancer (including adenocarcinoma in situ) was 4.0% (103/2552). Morbidity among doctors, nurses, technicians, administers, and logistics was no difference (p = 0.184), but higher in women than in men (4.7% vs 2.4% p = 0.002). The invasiveness increased with age and CT density of nodules (p = 0.018). The relationship between lung cancer morbidity and PM2.5 was not clear (p = 0.543); and no lung cancer has been found in employees related ionizing radiation. CONCLUSION: The high screening rate has brought about a high incidence of lung cancer. At present, the risk factor analysis of lung cancer based on small samples cannot find the direct cause. Most of the ground glass opacity (GGO)s detected by LDCT screening are indolent, but there are also rapidly progressive lung cancer. A predictive model to identify active and indolent GGO is necessary.

Dynamic 18 F-FDG PET/CT can predict the major pathological response to neoadjuvant immunotherapy in non-small cell lung cancer.

Major pathological response (MPR) is a potential surrogate for overall survival. We determined whether the dynamic changes in 18 F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) were associated with MPR in patients receiving neoadjuvant immunotherapy. Forty-four patients with stage II-III non-small cell lung cancer (NSCLC) who received neoadjuvant immunotherapy and radical surgery were enrolled. Moreover, 18 F-FDG PET/CT scans were performed at baseline and within 1 week before surgery to evaluate the disease. All histological sections were reviewed to assess MPR. The detailed clinical features of the patients were analyzed. The reliability of the clinical variables was assessed in differentiating between MPR and non-MPR using logistic regression. Receiver-operating characteristic (ROC) curve analysis identified the SUVmax changes threshold most associated with MPR. Most of the patients were pathologically diagnosed with squamous cell carcinoma and received anti-PD-1 antibodies plus chemotherapy. The immunotherapy regimens included nivolumab, pembrolizumab, and camrelizumab. MPR was observed in more than half of lesions. Tumors with MPR had a higher decrease in the longest dimension on dynamic PET/CT than those without MPR. Furthermore, the decline in SUVmax was significantly different between MPR and non-MPR diseases, and MPR lesions had a prominent mean reduction in SUVmax. SUVmax reduction was independently associated with MPR in the multivariate regression. On ROC analysis, the threshold of SUVmax decrease in 60% was associated with MPR. Dynamic changes in SUVmax were associated with MPR. The tumors with MPR showed a greater PET/CT response than those without MPR. A SUVmax decrease of more than 60% is more likely to result in an MPR after receiving neoadjuvant immunotherapy.

A novel four-gene signature for predicting the prognosis of hepatocellular carcinoma.

OBJECTIVE: To identify and utilize gene signatures for the prognostic evaluation of postoperative patients with hepatocellular carcinoma (HCC). METHODS: The gene mRNA expression profiles and corresponding clinicopathological data of postoperative patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Highly differentially expressed genes (DEGs) in tumor tissues compared to adjacent tissues were identified, and their associations with the overall survival (OS) of HCC patients were analyzed. The strongly associated genes were used to develop a prognostic score for the survival stratification of HCC, and the underlying mechanisms were analyzed using bioinformatics. RESULTS: A total of 376 DEGs were identified and four DEGs (ADH4, COL15A1, RET and KCNJ16) were independently associated with OS. A prognostic score derived from the four genes could effectively stratify HCC patients with different OS outcomes, independent of clinical parameters. Patients with high scores exhibited poorer OS than patients with low scores (HR 5.526, 95% CI: 2.451-12.461, p < .001). The four genes were involved in cancer-related biological processes and were independent of each other in bioinformatics analyses. CONCLUSION: Four genes strongly associated with the prognosis of postoperative patients with HCC were identified, and the derived prognostic score was simple and valuable for overall survival prediction.

Comprehensive Analysis of the Immune Implication of TEX41 in Skin Cutaneous Melanoma.

Enhancer RNAs (eRNAs), a subclass of noncoding RNAs from enhancers, have been demonstrated to exhibit important regulatory effects on the expressions of various genes. However, the role of eRNAs in skin cutaneous melanoma (SKCM) remained largely unclear. In this study, we aimed to explore the expression and prognostic value of an enhancer RNA TEX41 in SKCM as well as the associations between TEX41 and tumor-infiltrating immune cells (TICs). We observed that TEX41 expression was distinctly increased in SKCM specimens compared with normal skin specimens using GEPIA. Survival assays based on TGCA datasets revealed that patients with low TEX41 expressions displayed a longer overall survival than those with high TEX41 expression. CIBERSORT datasets revealed that TEX41 was related to 8 types of TICs (macrophages M1, T cells regulatory, plasma cells, mast cells resting, T cells CD8, dendritic cells resting, and T cells follicular helper). Three kinds of TICs were negatively related to TEX41 expressions, including macrophages M2, NK cells resting, and macrophages M0. The expressions of TEX41 were involved in five KEGG pathways, including transcriptional misregulation in cancer, SNARE interactions in vesicular transport, mitophagy-animal, melanoma, melanogenesis, and progesterone-mediated oocyte maturation. Overall, TEX41 can be used as a novel biomarker for the prognosis of SKCM patients and is associated with TICs, indicating it as a therapeutic target for SKCM.

Occurrence, removal and mass loads of antiviral drugs in seven wastewater treatment plants with various treatment processes.

Antiviral drugs are among the most common and important classes of pharmaceuticals to treat viral infections, however their continuous emission and persistence in the receiving environment has attracted increasing attention about their potential ecological risks. Here we investigated the occurrence, fate and mass load of 9 antiviral drugs for acquired immunodeficiency syndrome and hepatitis B, in 7 wastewater treatment plants (WWTPs) with different treatment processes in Guangdong, China. Totally, 8 target antiviral drugs were detected in the WWTPs influent wastewater, effluent wastewater and sludge, with maximal concentrations up to 7624 ng/L (telbivudine), 568 ng/L (telbivudine), and 2013 ng/g wet weight (telbivudine), respectively. The removal efficiency varied widely between different antiviral drugs, with the mean aqueous removal efficiency and total removal efficiency ranging from -6.2% (nevirapine) to 100% (lamivudine) and -1.2% (nevirapine) to 100% (lamivudine), respectively. Mass balance analysis showed that their elimination was mostly attributed to the biodegradation/biotransformation. The total back-estimated usage and emission of 9 target antiviral drugs were 77.8 t/y and 13.2 t/y in Guangdong province, China, respectively. Based on the sewage epidemiology approach, the consumption and emission of antiviral drugs in seven studied WWTPs were ranged at 2.31 mg/d/1000 people (nevirapine) to 4970 mg/d/1000 people (telbivudine), and 0 (lamivudine) to 900 mg/d/1000 people (telbivudine), respectively. Preliminary risk assessment showed that the antiviral drugs of zidovudine, ritonavir, lopinavir, and telbivudine in the receiving rivers could pose high ecological risks for aquatic environment. The findings from the present study illustrate the persistence of nevirapine in WWTPs, and provide essential evidence for further study into the development of wastewater treatment technologies.

B Vitamins Supplementation Can Improve Cognitive Functions and May Relate to the Enhancement of Transketolase Activity in A Rat Model of Cognitive Impairment Associated with High-fat Diets.

OBJECTIVE: To determine whether B vitamin treatment was sufficient to reduce cognitive impairment associated with high-fat diets in rats and to modulate transketolase (TK) expression and activity. METHODS: To test this, we separated 50 rats into five groups that were either fed a standard chow diet (controls) or a high-fat diet (experimental groups H0, H1, H2, and H3). H0 group animals received no additional dietary supplementation, while H1 group animals were administered 100 mg/kg body weight (BW) thiamine, 100 mg/kg BW riboflavin, and 250 mg/kg BW niacin each day, and group H2 animals received daily doses of 100 mg/kg BW pyridoxine, 100 mg/kg BW cobalamin, and 5 mg/kg BW folate. Animals in the H3 group received the B vitamin regimens administered to both H1 and H2 each day. RESULTS: Over time, group H0 exhibited greater increases in BW and fat mass relative to other groups. When spatial and memory capabilities in these animals were evaluated via conditioned taste aversion (CTA) and Morris Water Maze (MWM), we found B vitamin treatment was associated with significant improvements relative to untreated H0 controls. Similarly, B vitamin supplementation was associated with elevated TK expression in erythrocytes and hypothalamus of treated animals relative to those in H0 (P<0.05). CONCLUSION: Together, these findings suggest B vitamin can modulate hypothalamic TK activity to reduce the severity of cognitive deficits in a rat model of obesity. As such, B vitamin supplementation may be a beneficial method for reducing cognitive dysfunction in clinical settings associated with high-fat diets.

LncRNA LINC00355 promotes EMT and metastasis of bladder cancer cells through the miR-424-5p/HMGA2 axis.

Bladder cancer is a common malignant tumor with a high recurrence rate and mortality, while the detailed mechanisms for bladder cancer progression and metastasis are unknown. Recently, long non-coding RNAs (lncRNAs) have been reported to be involved in the development of cancers. In this study, we aim to investigate the role of lncRNA LINC00355 in bladder cancer progression and metastasis. The association between LINC00355 and the prognosis of bladder cancer patients was determined by Kaplan-Meier survival analysis. Cell migration and invasion ability were detected using the Transwell migration and invasion assay. The relationships of LINC00355, miR-424-5p, and High Mobility Group AT-Hook 2 (HMGA2) were verified through the luciferase assay and RNA pull-down assay. Xenograft tumor was established to evaluate tumor lung metastasis in vivo. qRT-PCR and western blot were used to detect gene expression. LINC00355 was upregulated in bladder cancer patients, especially in patients with higher TNM stage. Elevated LINC00355 was correlated with the poor prognosis of bladder cancer patients. Besides, overexpressed LINC00355 promoted migration, invasion, and epithelial-mesenchymal transition (EMT) ability of bladder cancer cells. Contrarily, decreased LINC00355 suppressed migration, invasion, and EMT ability of bladder cancer cells, and lung metastasis of xenograft tumors. Furthermore, LINC00355 could regulate HMGA2 expression by acting as a sponge for miR-424-5p. Overexpression of HMGA2 induced EMT of bladder cancer cells. Additionally, LINC00355 regulated the migration, invasion, and EMT ability of bladder cancer cells through modulating HMGA2 expression via sponging miR-424-5p. LINC00355 promoted migration, invasion, and EMT ability of bladder cancer through elevating HMGA2 expression via acting as a sponge for miR-424-5p.

Blood-derived molecular signatures as biomarker panels for the early detection of colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of tumor morbidity and mortality worldwide. Endoscopy is currently the main screening method, but the invasiveness and high cost hamper the application of endoscopy in asymptomatic patients with a risk of CRC and lead to a low diagnostic rate for early CRC. In recent years, the progress of transcriptomics, epigenetics, immunomics and metabolomics has greatly contributed to the identification of novel molecular markers for the noninvasive screening of CRC, and many molecules in various biological processes have been identified and evaluated for CRC detection. However, individual molecules always have insufficient diagnostic performance as biomarkers for the detection of CRC; therefore, a frequent strategy to overcome this deficiency is the use of molecule signatures as biomarker panels to improve the diagnostic power. Here, we reviewed the diagnostic performance of blood-derived molecular signatures (mRNAs, microRNAs, autoantibodies, and metabolites) as biomarker panels for CRC detection, particularly for early detection, and discussed their limitations and prospects.

Cytoskeleton-associated membrane protein 4 is upregulated in tumor tissues and is associated with clinicopathological characteristics and prognosis in hepatocellular carcinoma.

The role of cytoskeleton-associated membrane protein 4 (CKAP4) in hepatocellular carcinoma (HCC) is controversial. The present study aimed to investigate the association between tumor CKAP4 mRNA expression and clinicopathological characteristics and prognosis in patients with HCC. Data relating to CKAP4 mRNA expression in HCC tumor and normal adjacent liver tissues, and clinicopathological characteristics, were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The CKAP4 mRNA levels in tumor tissues were compared with those in normal adjacent liver tissues, their association with clinicopathological parameters was analyzed, and diagnostic and prognostic values were evaluated in patients with HCC. In all 4 datasets (total samples, n=693), CKAP4 mRNA levels were significantly higher in tumor tissues compared with adjacent tissues (all P<0.001), with the area under the receiver operating characteristic curve ranging from 0.799-0.898 for HCC diagnosis. In patients with HCC with available clinical data (n=361), the low-level CKAP4 mRNA group exhibited a lower body mass index (P=0.005), higher α-fetoprotein level (P<0.001), more frequent adjacent liver tissue inflammation (P<0.001), poorer tumor histological grade (P<0.001), higher Ishak fibrosis score (P=0.035) and a more advanced tumor node metastasis (TNM) stage (P=0.014) compared with the high-level CKAP4 mRNA group. Patients stratified by all the above parameters, except for TNM stage, exhibited significantly different expression of tissue CKAP4 mRNA (P<0.05-0.001). Furthermore, higher CKAP4 mRNA levels were observed in patients who died within one year following diagnosis compared with those who survived >3 years (P=0.003). The high-level CKAP4 mRNA group also exhibited lower overall survival (OS) and disease-free survival (DFS) rates compared with the low-level group [hazard ratio (HR)=1.494; 95% confidence interval (CI), 1.044-2.138; P=0.028] for OS and (HR=1.616; 95% CI, 1.022-2.555; P=0.040) for DFS. The results of the present study suggest that CKAP4 mRNA is upregulated in HCC tumor tissues compared with normal adjacent tissues, and is associated with poor clinical prognosis, pathological features and survival in patients with HCC. Thus, CKAP4 is a potential biomarker for HCC diagnosis and prognosis.

In vitro genotoxicity study of silver nanoparticles and titanium dioxide nanoparticles.

Nanoparticles are widely used in cosmetic, pharmaceutical, and food industries, but their safety and genetic toxicity are still unclear. In this study, the genotoxicity of silver nanoparticles (AgNPs) and titanium dioxide nanoparticles (titanium dioxide nanoparticles) were evaluated by in vitro comet assay and PIG-A assay in TK6 cells. We exposed TK6 cells to two types of nanoparticles at the highest concentration of 200 µmol/L for 4 h and conducted the in vitro comet assay. We examined the mutation results of PIG-A gene in vitro after 4 h, 24 ho and 10 days of exposure, respectively. We also examined the endocytosis of nanoparticles in TK6 cells exposed to nanoparticles for 24 h. In the endocytosis assay, with the increase of nano-material concentration, the side scatter (SSC) of TK6 cells in flow cytometry showed a concentration-dependent and time-dependent increase, indicating that TK6 cells could uptake both types of nanoparticles. In the comet assay, AgNPs could induce a concentration-dependent increase in DNA tail intensity. However, titanium dioxide NPs could not induce the concentration-dependent increase of DNA fluorescence intensity of comet tail. In the PIG-A assay, both AgNPs and TiO2NPs did not induce PIG-A gene mutation frequency in TK6 cells. The results showed that AgNPs could induce DNA damage in TK6 cells, but could not induce increase of PIG-A gene mutation frequency. TiO2NPs neither induce DNA damage in TK6 cells nor increase PIG-A mutation frequency. Further tests are needed to determine whether TiO2NPs are genotoxic.

miR-10b suppresses cell invasion and metastasis through targeting HOXA3 regulated by FAK/YAP signaling pathway in clear-cell renal cell carcinoma.

BACKGROUND: MicroRNAs have been related to tumor progression in diverse human cancers including clear-cell renal cell carcinoma (ccRCC). Previous study has suggested the important regulation function of miR-10b in ccRCC. However, the direct target of miR-10b in ccRCC and the related molecular mechanisms has not yet been revealed. METHODS: miR-10b and HOXA3 was detected by qRT-PCR. MTT, colony formation assay, wound-healing and transwell assays were performed to detect cell proliferation, colony formation, migration, and invasion abilities in ccRCC. Western blot analyses were performed to evaluate the protein expression of HOXA3, YAP, FAK and MMP-9. Dual luciferase reporter assay was employed to measure potential molecular mechanism of miR-10b in ccRCC. RESULTS: miR-10b was down-regulated in 786-O and A498 cells as compared to renal tubular HK-2 cells. By contrast, HOXA3 and YAP was up-regulated in ccRCC cells and tissues. Functionally, knockdown of YAP inhibited cell proliferation, migration and invasion. Knockdown of FAK downregulated YAP, in turn, resulted in a decrease of HOXA3 expression. Mechanically, miR-10b targets HOXA3 to exert its tumor-suppressive effect on ccRCC in vitro. CONCLUSIONS: These novel data suggest that miR-10b suppresses cell invasion and metastasis through targeting HOXA3, which partially passed through the FAK/YAP signaling pathway.