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Abstract Background Non-small cell lung cancer (NSCLC) accounts for the vast majority of lung cancers. Early detection is crucial to reduce lung cancer-related mortality. Aberrant DNA methylation occurs early during carcinogenesis and can be detected in blood. It is essential to investigate the dysregulated blood methylation markers for early diagnosis of NSCLC. Methods NSCLC-associated methylation gene folate receptor gamma (FOLR3) was selected from an Illumina 850K array analysis of peripheral blood samples. Mass spectrometry was used for validation in two independent case–control studies (validation I: n = 2548; validation II: n = 3866). Patients with lung squamous carcinoma (LUSC) or lung adenocarcinoma (LUAD), normal controls (NCs) and benign pulmonary nodule (BPN) cases were included. FOLR3 methylations were compared among different populations. Their associations with NSCLC clinical features were investigated. Receiver operating characteristic analyses, Kruskal–Wallis test, Wilcoxon test, logistics regression analysis and nomogram analysis were performed. Results Two CpG sites (CpG_1 and CpG_2) of FOLR3 was significantly lower methylated in NSCLC patients than NCs in the discovery round. In the two validations, both LUSC and LUAD patients presented significant FOLR3 hypomethylations. LUSC patients were highlighted to have significantly lower methylation levels of CpG_1 and CpG_2 than BPN cases and LUAD patients. Both in the two validations, CpG_1 methylation and CpG_2 methylation could discriminate LUSC from NCs well, with areas under the curve (AUCs) of 0.818 and 0.832 in validation I, and 0.789 and 0.780 in validation II. They could also differentiate LUAD from NCs, but with lower efficiency. CpG_1 and CpG_2 methylations could also discriminate LUSC from BPNs well individually in the two validations. With the combined dataset of two validations, the independent associations of age, gender, and FOLR3 methylation with LUSC and LUAD risk were shown and the age-gender-CpG_1 signature could discriminate LUSC and LUAD from NCs and BPNs, with higher efficiency for LUSC. Conclusions Blood-based FOLR3 hypomethylation was shown in LUSC and LUAD. FOLR3 methylation heterogeneity between LUSC and LUAD highlighted its stronger associations with LUSC. FOLR3 methylation and the age-gender-CpG_1 signature might be novel diagnostic markers for the early detection of NSCLC, especially for LUSC.

PurposePrevious studies have shown that DNA methylation in peripheral blood may be associated with breast cancer (BC). To explore the association between the methylation level of the Cathepsin Z (CTSZ) gene in peripheral blood and BC, we conducted a case–control study in the Chinese population.MethodsPeripheral blood samples were collected from 567 BC cases, 635 healthy controls, and 303 benign breast disease (BBD) cases. DNA extraction and bisulfite-specific PCR amplification were performed for all samples. The methylation levels of seven sites of the CTSZ gene were quantitatively determined by Mass spectrometry. The odds ratios (ORs) of CpG sites were evaluated for BC risk using per 10% reduction and quartiles analyses by logistic regression.ResultsOur analysis showed that five out of the seven CpG sites exhibited significant associations with hypomethylation of CTSZ and BC, compared to healthy controls. The highest OR was for Q2 of CTSZ_CpG_1 (OR: 1.62, P=0.006), particularly for early-stage breast cancer in the case of per 10% reduction of CTSZ_CpG_1 (OR: 1.20, P=0.003). We also found that per 10% reduction of CTSZ_CpG_5 (OR: 1.39, P=0.004) and CTSZ_CpG_7,8 (OR: 1.35, P=0.005) were associated with increased BC risk. Our study also revealed that four out of seven CpG sites were linked to increased BC risk in women under 50 years of age, compared to healthy controls. The highest OR was for per 10% reduction of CTSZ_CpG_1 (OR: 1.47, P

Abstract Background Cervical cancer shows great differences in depth of invasion, metastasis, and other biological behaviors. The location of the lesion is special, so it is usually difficult to determine the clinical stage. This study aimed to explore the clinical value of magnetic resonance imaging (MRI) and tumor serum markers for the preoperative diagnosis of cervical cancer lymph node metastasis and para-uterine invasion. Methods A total of 200 patients with cervical cancer admitted to our hospital from January 2019 to January 2020 were collected as the research subjects. Comparing the diagnosis results of preoperative MRI scan, serum tumor markers, and postoperative pathological examination using single factor comparison, we determined the MRI scan results, the comprehensive matching rate between serum tumor markers (squamous cell carcinoma antigen (SCCA), carbohydrate antigen 125 (CA125)) and postoperative pathological results, and the differences of sensitivity, specificity, and accuracy in the prediction of lymph node metastasis and para-uterine infiltration of cervical cancer. Results The levels of SCCA and CA125 in patients with para-uterine invasion and lymph node metastasis were higher than those of patients without invasion and metastasis. Among them, the level of SCCA was significantly different (P0.05), so MRI combined with serum SCCA was selected for combined diagnosis in the later period. The sensitivity, specificity, and accuracy of MRI diagnosis of cervical cancer and para-uterine infiltrating lymph node metastasis and metastasis were 55.2, 91.6, and 89.5% and 55.2, 91.6, and 89.5%, respectively. These data in MRI combined with serum SCCA were 76.3, 95.3, and 94.3% and 63.2, 96.0, and 95.1%, respectively. The accuracy of tumor markers combined with MRI in the diagnosis of cervical cancer lymph node metastasis and para-uterine invasion was higher than that of MRI. Conclusions MRI combined with serum SCCA can more accurately identify cervical cancer lymph node metastasis and para-uterine invasion compared with MRI alone. Tumor marker combined with MRI diagnosis is an important auxiliary method for cervical cancer treatment and can provide comprehensive and reliable clinical evidence for evaluation before cervical cancer surgery.

Snow pea is a very important vegetable, and its postharvest storage characteristics vary with species. Few studies on the differences in its storage characteristics are available. In this study, postharvest changes in metabolic rate (respiration rate and water loss rate), membrane permeability (relative conductivity), nutrient contents (total sugar, amino acids, starch), lignin, cellulose, β-Glucosidase (β-GC) enzyme activity, texture properties, PG enzyme activity and their relationship were analyzed in large sweet broad peas and small snow peas. On the 8th day of storage, we found that the respiration rate and water loss rate were increased, total sugars and total amino acids were decreased significantly in these two legume vegetables, and that metabolic rate was slower with less nutrients consumed in large sweet broad peas than in small snow peas. Throughout the 8-day whole storage, the lignin and cellulose contents were always lower in large sweet broad peas than in small snow peas. With the increasing storage time, small snow peas were more susceptible to lignification and fibrosis, which was observed in their texture properties. The enzyme activities related to cellulose and pectin degradation (β-GC, PG) also showed the same trend during the storage. At the late stage of storage, the taste of large sweet broad peas was better than that of small snow peas. In conclusion, the storage period of large sweet broad peas was longer than that of the small snow peas, and its lignification degree was lower than that of the small snow peas. Meanwhile, senescence and lignin accumulation led to hardening of snow pea during postharvest storage. Our findings provide a theoretical reference for improving the postharvest storage quality of snow pea and extending the shelf life.

Accumulating evidence has uncovered long non-coding RNAs (lncRNAs) as central regulators in the pathogenesis of diverse human cancers including colorectal cancer (CRC). The present study discovered that a novel lncRNA ITIH4 antisense RNA 1 (ITHI4-AS1) was frequently under-expressed in most normal human tissues, including colon tissues. Therefore, we aimed to investigate the role of ITHI4-AS1 in CRC. Interestingly, a significant overexpression of ITIH4-AS1 was observed in CRC cell lines relative to normal NCM460 cells. Also, we investigated the facilitating role of ITIH4-AS1 in CRC cell growth and metastasis both in vitro and in vivo. Additionally, we explained that ITIH4-AS1 upregulation in CRC was attributed to downregulation or even depletion of RE1 silencing transcription factor (REST), a presently identified transcriptional repressor for ITIH4-AS1. Meanwhile, the contribution of ITIH4-AS1 to CRC development was validated to rely on the activation of the JAK/STAT3 pathway. More importantly, we verified that FUS interacted with both ITIH4-AS1 and STAT3, and that ITIH4-AS1 evoked nuclear translocation of phosphorylated (p)-STAT3 in CRC through recruiting FUS. In summary, our findings unveiled for the first time that REST downregulation-enhanced ITIH4-AS1 exerts pro-tumor functions in CRC through FUS-dependent activation of the JAK/STAT3 pathway, implying that targeting ITIH4-AS1 may be a novel effective strategy for CRC therapy. Keywords: ITIH4-AS1, colorectal cancer, REST, FUS, STAT3

Honey peach (Prunus persica L.) is highly nutritious; it is an excellent source of sugars, proteins, amino acids, vitamins, and mineral elements. However, it is a perishable climacteric fruit that is difficult to preserve. In this study, “Feicheng” honey peach fruit was used as a test material to investigate the synergistic preservation effect of 1-methylcyclopropene (1-MCP) and laser microporous film (LMF). The peach fruits were fumigated for 24 h with 2 μL L−1 1-MCP, then packed in LMF. In comparison with the control treatment, 1-MCP + LMF treatment markedly decreased the respiration rate, weight loss, and rot rate of peach fruits. Moreover, the combination of 1-MCP and LMF suppressed the increase in soluble solids (SS) and reducing sugars (RS), as well as the decrease in titratable acid (TA) and ascorbic acid (AsA). The combined application also maintained a high protopectin content and low soluble pectin content; it reduced the accumulation of superoxide anions (O2−) and hydrogen peroxide (H2O2). Except in a few samples, the catalase (CAT) and ascorbate peroxidase (APX) activities were higher when treated by 1-MCP + LMF. Conversely, the phenylalanine deaminase (PAL), peroxidase (POD), lipase, lipoxygenase (LOX), polygalacturonase (PG), β-glucosidase, and cellulase (Cx) activities were lower than in the control. Furthermore, 1-MCP + LMF treatment reduced the relative abundances of dominant pathogenic fungi (e.g., Streptomyces, Stachybotrys, and Issa sp.). The combined treatment improved the relative abundances of antagonistic fungi (e.g., Aureobasidium and Holtermanniella). The results indicated that the co-application of 1-MCP and LMF markedly reduced weight loss and spoilage, delayed the decline of nutritional quality, and inhibited the physiological and biochemical metabolic activities of peach during storage. These changes extended its shelf-life to 28 days at 5 °C. The results provide a reference for the commercial application of this technology.

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) function as essential regulators in the development and progression of multiple tumors. However, the molecular mechanisms of MIR31HG in regulating ESCC progression remain unknown. Here, we confirmed that MIR31HG facilitated ESCC cells proliferation in vivo. Besides, MIR31HG knockdown increases the percentage of cells at the G1 phase, along with reduced arrest in S phase and MIR31HG overexpression exhibits the opposite effects. Overexpressed MIR31HG decreases the percentage of apoptotic ESCC cells. Interestingly, MIR31HG can function as a competing endogenous RNA by sponging miR-34a. The rescue experiments demonstrated that MIR31HG function is partially reversed by inhibiting miR-34a. In addition, we found c-Met is a target gene of miR-34a and is indirectly regulated by MIR31HG. Taken together, our findings revealed that MIR31HG promotes ESCC progression by regulating miR-34a/ c-Met axis and may provide a new prospective for exploration and understanding of the biological effects of esophageal squamous cell carcinoma.

Background/Aims: The Hippo-Yap pathway is associated with tumor development and progression. However, little evidence is available concerning its role in cancer cell apoptosis and migration via mitochondrial homeostasis. Here, we identify mitochondrial fission as a regulator of the Hippo–Yap pathway in human rectal cancer tumorigenesis and metastasis. Methods: In this study, we performed loss-of function assays concerning Yap in RCC via shRNA. Cellular viability and apoptosis were measured via MTT, the TUNEL assay and trypan blue staining. Mitochondrial function was assessed via JC1 staining, the mPTP opening assay, mitochondrial respiratory function analysis, electron microscopy and immunofluorescence analysis of HtrA2/Omi. Mitophagy and mitochondrial fission were assessed via western blots and immunofluorescence. Cell migration was evaluated via the Transwell assay, wound-healing assay and immunofluorescence analysis of F-actin. The interaction between JNK and Yap was detected via co-immunoprecipitation and Yap recombinant mutagenic plasmid transfection. Western blots were used to analyze signaling pathways in conjunction with JNK inhibitors or HtrA2/Omi siRNA. Results: Yap is upregulated in human rectal cancer cells, where its expression correlates positively with cell survival and migration. Functional studies established that silencing of Yap drove JNK phosphorylation, which induced Drp1 activation and translocation to the surface of mitochondria, initiating mitochondrial fission. Excessive mitochondrial fission mediated HtrA2/Omi leakage from the mitochondria into the cytoplasm, where HtrA2/Omi triggered cellular apoptosis via the mitochondrial apoptosis pathway. Moreover, released HtrA2/Omi also phosphorylated cofilin and inhibited cofilin-mediated F-actin polymerization. F-actin collapse perturbed lamellipodia formation and therefore impaired cellular migration and invasion. Conclusion: Collectively, our results demonstrate that Hippo-Yap can serve as a tumor promoter in human rectal cancer and acts by restricting JNK/Drp1/mitochondrial fission/ HtrA2/Omi, with potential implications for new approaches to human rectal cancer therapy.

Exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSCs) expressing microRNAs (miRs) have been highlighted as important carriers for gene or drug therapy. Hence, this study aimed to explore the role of exosomal miR-148b-3p from HUCMSCs in breast cancer. Clinical samples subjected to RT-qPCR detection revealed that miR-148b-3p was poorly expressed, while tripartite motif 59 (TRIM59) was highly expressed in breast cancer tissues. Online analyses available at miRanda, TargetScan, and miRbase databases revealed that miR-148b-3p could bind to TRIM59, while dual-luciferase reporter gene assay further verified that TRIM59 was a target gene of miR-148b-3p. Next, miR-148b-3p mimic or inhibitor and siRNA against TRIM59 were delivered into the breast cancer cells (MDA-MB-231) to alter the expression of miR-148b-3p and TRIM59 so as to evaluate their respective effects on breast cancer cellular processes. Evidence was obtained demonstrating that miR-148b-3p inhibited cell proliferation, invasion, and migration, but promoted cell apoptosis in breast cancer by down-regulating TRIM59. Next, MDA-MB-231 cells were co-cultured with the exosomes derived from HUCMSCs expressing miR-148b-3p. The results of co-culture experiments demonstrated that HUCMSCs-derived exosomes carrying miR-148b-3p exerted inhibitory effects on MDA-MB-231 progression in vitro. In vivo experimentation further confirmed the anti-tumor effects of HUCMSCs-derived exosomes carrying miR-148b-3p. Taken together, HUCMSC-derived exosomes carrying miR-148b-3p might suppress breast cancer progression, which highlights the potential of exosomes containing miR-148b-3p as a promising therapeutic approach for breast cancer treatment.

Background: Long non-coding RNAs (lncRNAs) are powerful factors influencing the tumorigenesis and metastasis of multiple carcinomas. LncRNA MNX1-AS1 plays critical roles in the progression of tumor formation according to recent research, while its roles in esophageal squamous cell carcinoma (ESCC) remains unknown. Methods: The expression levels of lncRNA MNX1-AS1 were examined in ESCC tissues by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The role of lncRNA MNX1-AS1 was performed by WST-1 proliferation assays, migration and invasion assays. Besides, the molecular mechanism of lncRNA MNX1-AS1 was verified by online bioinformatics, qRT-PCR and rescue assays. Results: MNX1-AS1 was signifcantly upregulated in ESCC tissues. It was conformed that high MNX1-AS1 expression was associated with ESCC lymph node metastasis. Moreover, we found that knockdown of MNX1-AS1 apparently suppressed the cell proliferation, migration, and invasion capacity. Flow cytometry analysis showed MNX1-AS1 regulated ESCC cell cycle and apoptosis progression. Mechanism analysis revealed that miR-34a inhibitor could rescue the influence of inhibiting MNX1-AS1 on ESCC cells migration by serving as competing endogenous RNA (ceRNAs). Furthermore, we found that miR-34a specifically targeted SIRTI. Conclusions: Taken together, we demonstrated that lncRNA MNX1-AS1/miR-34a/SIRT1 regulatory axis could play an important role in ESCC progression, and MNX1-AS1 may act as a novel potential biomarker for esophageal squamous cell carcinoma.

Increasing evidence has demonstrated that histone deacetylase 2 (HDAC2) participates in the regulation of a variety of biological processes in numerous tumors. However, the potential role of HDAC2 in the development and progression of esophageal squamous cell carcinoma (ESCC) remains elusive. Immunohistochemistry was utilized to detect the expression of HDAC2, Cell Counting Kit-8 was used to determine the cell proliferation, and flow cytometry was employed to investigate cell cycle and cell apoptosis. Finally, western blotting was employed to detect the protein expression of cyclin D1, p21, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). The present study found that expression of HDAC2 protein in ESCC tissues was significantly increased compared with atypical hyperplasia tissues and normal esophageal mucosa (P<0.001). The expression of HDAC2 was not associated with the age or gender of patients (P>0.05), but was closely associated with the histological grade, invasion depth, tumor-node-metastasis stage and lymph node metastasis, respectively (all P<0.001). HDAC2 small interfering RNA effectively downregulated the expression of HDAC2 protein in ESCC EC9706 cells. Downregulation of HDAC2 expression evidently inhibited cell proliferation, arrested cell cycle at the G0/G1 phase and induced cell apoptosis in ESCC EC9706 cells, coupled with increased expression of p21 and Bax proteins and decreased expression of cyclin D1 and Bcl-2 proteins. Overall, the present findings suggest that HDAC2 may play an important role in the development and progression of ESCC and be considered as a novel molecular target for the treatment of ESCC. [ABSTRACT FROM AUTHOR]