From CNN to Transformer: A Review of Medical Image Segmentation Models.

Medical image segmentation is an important step in medical image analysis, especially as a crucial prerequisite for efficient disease diagnosis and treatment. The use of deep learning for image segmentation has become a prevalent trend. The widely adopted approach currently is U-Net and its variants. Moreover, with the remarkable success of pre-trained models in natural language processing tasks, transformer-based models like TransUNet have achieved desirable performance on multiple medical image segmentation datasets. Recently, the Segment Anything Model (SAM) and its variants have also been attempted for medical image segmentation. In this paper, we conduct a survey of the most representative seven medical image segmentation models in recent years. We theoretically analyze the characteristics of these models and quantitatively evaluate their performance on Tuberculosis Chest X-rays, Ovarian Tumors, and Liver Segmentation datasets. Finally, we discuss the main challenges and future trends in medical image segmentation. Our work can assist researchers in the related field to quickly establish medical segmentation models tailored to specific regions.

Circ_0001944 depletion inhibits glycolysis and esophageal cancer progression by binding to miR-338-5p to reduce PDK1 expression.

Circular RNA (circRNA) plays multiple roles in the development of esophageal cancer (EC). Herein, we investigate the function of circ_0001944 in EC progression and the related mechanism. Expression of circ_0001944, microRNA-338-5p (miR-338-5p), pyruvate dehydrogenase kinase 1 (PDK1), E-cadherin and N-cadherin was analyzed by quantitative real-time polymerase chain reaction, Western blotting or immunohistochemistry assay. Cell viability, proliferation, apoptosis, invasion and migration were investigated by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell invasion and wound-healing assays, respectively. Glucose consumption was detected by Glucose Assay Kit. Lactate production was analyzed by Lactate Assay Kit. ATP/ADP ratio was determined by ADP/ATP ratio Assay Kit. The associations among circ_0001944, miR-338-5p and PDK1 were identified by dual-luciferase reporter and RNA pull-down assays. Xenograft mouse model assay was used to explore the role of circ_0001944 on tumor tumorigenesis in vivo. Circ_0001944 and PDK1 expression were significantly upregulated, while miR-338-5p was downregulated in EC tissues and cells in contrast with normal esophageal tissues and cells. Circ_0001944 knockdown inhibited EC cell proliferation, invasion, migration and glycolysis but induced apoptosis. Meanwhile, circ_0001944 depletion suppressed tumor tumorigenesis in vivo. Mechanistically, circ_0001944 bound to miR-338-5p, and miR-338-5p targeted PDK1. In addition, miR-338-5p inhibitors attenuated circ_0001944 depletion-induced effects in EC cells. The regulation of miR-338-5p on EC progression involved the downregulation of PDK1. Further, circ_0001944 controlled PDK1 expression through miR-338-5p. Circ_0001944 knockdown inhibited EC development and glycolysis by regulating the miR-338-5p/PDK1 pathway, providing a promising target for EC therapy.

IDO1 facilitates esophageal carcinoma progression by driving the direct binding of NF-κB and CXCL10.

Esophageal carcinoma (EC), one of the most lethal human malignancies, lacks effective targeted therapies. Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in a variety of cancers, but its role and mechanism in EC are still unclear. Immunohistochemistry and qRT-PCR were used to analyze the expression of IDO1 in EC, and the prognostic value of IDO1 in EC was evaluated by Kaplan-Meier test. The in vitro and in vivo function loss/acquisition tests were performed to evaluate the biological effects of IDO1 in EC. The mechanism of action of IDO1-regulation EC was explored through Firefly luciferase & Renilla luciferase activity reporter, chromatin immunoprecipitation (ChIP) and immunofluorescence (IF) assays. Clinically, IDO1 expression was abnormally elevated in EC and positively correlated with overall survival. Functionally, IDO1 was contributed to the proliferation and migration of EC cells. Mechanically, IDO1 regulated the expression of chemokine C-X-C ligand 10 (CXCL10) by promoting the entry of NF-κB into the nucleus to combine with the promoter of CXCL10. Consistently, IDO1 facilitated EC progression may dependent on the presence of CXCL10. Moreover, NF-κB alleviated the inhibitory effect of IDO1 knockdown on EC. IDO1 drove the progression of EC by directly binding NF-κB and CXCL10, the finding that may provide an effective theoretical basis for precise therapies for EC.

LincRNA-P21 knockdown facilitates esophageal squamous cell carcinoma cell progression by upregulating cadherin 5 via YTH domain containing 1.

LincRNA-P21 is a tumor suppressor in esophageal squamous cell carcinoma (ESCC). Cell adhesion modules play vital roles in cell-cell and cell-extracellular matrix (ECM) interactions and malignant cancer progression. In this study, we investigate whether lincRNA-P21 exerts its functions by regulating the cell adhesion molecule cadherin 5 (CDH5) in ESCC. Moreover, the RNA binding protein (RBP) mediators of lincRNA-P21 and CDH5 are further examined. Cell viability, growth and migratory ability are assessed by calcein-AM/PI double staining, CCK-8, EdU, Transwell, and wound healing assays. The expression of collagen I and fibronectin is examined by immunofluorescence (IF). LincRNA-P21 and CDH5 are quantified by RT-qPCR and western blot analysis. Potential lincRNA-P21 targets are identified by RNA sequencing. RBPs that can interact with lincRNA-P21 and CDH5 are identified by RNA immunoprecipitation (RIP) assay. LincRNA-P21 knockdown increases cell viability, growth, cell migration, and collagen I and fibronectin expression in ESCC cells. LincRNA-P21 depletion induces the dysregulation of 316 genes, including CDH5, in TE-1 cells. CDH5 is identified as a downstream molecule of lincRNA-P21 given its close correlation with cell adhesion, ECM reconstruction, and cancer progression. LincRNA-P21 exerts its functions by negatively regulating CDH5 expression. YTH domain containing 1 (YTHDC1) mediates the regulatory effect of lincRNA-P21 on CDH5. LincRNA-P21 knockdown elevates cell viability and growth, promotes cell migration, and induces ECM reorganization by upregulating CDH5 via RBP YTHDC1 in ESCC.

Exosomal circ_0026611 contributes to lymphangiogenesis by reducing PROX1 acetylation and ubiquitination in human lymphatic endothelial cells (HLECs).

BACKGROUND: Esophageal squamous carcinoma (ESCC) is a common malignancy that originates in the digestive tract. Lymph node metastasis (LNM) is a complicated process, and tumor lymphangiogenesis has been reported to be associated with the spread of tumor cells to lymph nodes (LNs), including in ESCC. However, little is currently known about the mechanisms involved in lymphangiogenesis in ESCC tumors. According to previous literature, we know that hsa_circ_0026611 expresses at a high level in serum exosomes of patients with ESCC and shows a close association with LNM and poor prognosis. However, details on the functions of circ_0026611 in ESCC remain unclear. We aim to explore the effects of circ_0026611 in ESCC cell-derived exosomes on lymphangiogenesis and its potential molecular mechanism. METHODS: We firstly examined how circ_0026611 may express in ESCC cells and exosomes by quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The potential effects circ_0026611 may exert on lymphangiogenesis in ESCC cell-derived exosomes were assessed afterward via mechanism experiments. RESULTS: circ_0026611 high expression pattern was confirmed in ESCC cells and exosomes. ESCC cell-derived exosomes promoted lymphangiogenesis by transferring circ_0026611. Besides, circ_0026611 interacted with N-α-acetyltransferase 10 (NAA10) to inhibit NAA10-mediated prospero homeobox 1 (PROX1) acetylation with subsequent ubiquitination and degradation. Furthermore, circ_0026611 was verified to promote lymphangiogenesis in a PROX1-mediated manner. CONCLUSIONS: Exosomal circ_0026611 inhibited PROX1 acetylation and ubiquitination to promote lymphangiogenesis in ESCC.

Association between the frequency of tooth brushing and esophageal carcinoma risk: an update systematic review and meta-analysis.

Background: Lower frequency of tooth brushing was thought to be associated with esophageal carcinoma (EC). However, some researchers suggested that this association did not exist or had not yet reached statistical significance. The purpose of this study was to calculate a more precise estimation of the relationship between the frequency of tooth brushing and the risk of EC by combining the results between different studies using the meta-analysis. Methods: We searched the PubMed, Embase, Web of Science, and Scopus electronic databases up to July 2021. According to PECO approach (Population, Exposure, Comparator and Outcomes), we assessed the association between tooth brushing frequency and EC risk which reported the adjusted risk ratios (adjRR), hazard ratios (adjHR), or odds ratios (adjOR) with 95% confidence interval (CI). The random effects model was used to quantitatively evaluate the combined results. Two researchers independently evaluated the risk bias of the included studies using the Newcastle-Ottawa Scale (NOS). The robustness of results was evaluated by subgroup analysis, sensitivity analysis, and publication bias. Results: In total, we identified 13 articles with 14 case-control studies which included 16,773 participants and 5,673 patients. Pooled results showed the lowest frequency of brushing was significantly associated with an increased risk of EC in comparison to the highest (adjOR: 2.00, 95% CI: 1.61-2.48). There was moderate heterogeneity among included studies (P=0.001, I2=61.4%). The original studies included in this meta-analysis were all case-control studies. Study quality was all moderate or above based on NOS score ranges of 6 stars or more. Conclusions: Available evidence suggests a low frequency of tooth brushing may be an important risk factor for EC. However, higher quality studies should continue to be conducted to investigate the optimal threshold of brushing frequency for the prevention of EC.

Identification of a novel circ_0001946/miR-1290/SOX6 ceRNA network in esophageal squamous cell cancer.

BACKGROUND: Circular RNAs (circRNAs) can function as competing endogenous RNAs (ceRNAs) to impact the development of esophageal squamous cell cancer (ESCC). Human circ_0001946 has been identified as a potential anticancer factor in ESCC, yet our understanding of its molecular basis remains limited. METHODS: Circ_0001946, microRNA (miR)-1290 and SRY-box transcription factor 6 (SOX6) were quantified by quantitative reasl-time PCR (qRT-PCR) or immunoblotting. Cell proliferation was assessed by CCK-8 and EDU assays. Cell apoptosis and invasion were evaluated by flow cytometry and transwell assays, respectively. Cell migration was detected by transwell and wound-healing assays. The direct relationship between miR-1290 and circ_0001946 or SOX6 was determined by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model assays were used to assess the role of circ_0001946 in tumor growth. RESULTS: Circ_0001946 expression was attenuated in human ESCC, and circ_0001946 increase impeded cell proliferation, invasion, migration and enhanced apoptosis in vitro. Moreover, circ_0001946 increase diminished xenograft growth in vivo. Mechanistically, circ_0001946 bound to miR-1290, and re-expression of miR-1290 reversed circ_0001946-dependent cell properties. SOX6 was a miR-1290 target and it was responsible for the regulation of miR-1290 in cell properties. Furthermore, circ_0001946 functioned as a ceRNA to regulate SOX6 expression via miR-1290. CONCLUSION: Our findings uncover an undescribed molecular mechanism, the circ_0001946/miR-1290/SOX6 ceRNA crosstalk, for the anti-ESCC activity of circ_0001946.

Circular RNA CircPVT1 Inhibits 5-Fluorouracil Chemosensitivity by Regulating Ferroptosis Through MiR-30a-5p/FZD3 Axis in Esophageal Cancer Cells.

BACKGROUND: CircPVT1 is demonstrated to promote cancer progression in esophageal squamous cell carcinoma (ESCC). However, the role and potential functional mechanisms of circPVT1 in regulating 5-fluorouracil (5-FU) chemosensitivity remain largely unknown. METHODS: ESCC cells resistant to 5-FU were induced with continuous increasing concentrations of 5-FU step-wisely. A cell counting kit-8 assay was used to analyze the viability of ESCC cells. LDH release assay kit was used to evaluate the cytotoxicity. RT-qPCR was used to assess the expression level of non-coding RNAs and cDNAs. Luciferase was used to confirm the interaction between non-coding RNAs and targets. Western blotting was used to detect the expression of downstream signaling proteins. Flow cytometry and ferroptosis detection assay kit were utilized to measure the ferroptosis of ESCC cells. RESULTS: CircPVT1 was significantly upregulated in ESCC cells resistant to 5-FU. Knockdown of circPVT1 enhanced the 5-FU chemosensitivity of ESCC cells resistant to 5-FU by increasing cytotoxicity and downregulating multidrug-resistant associated proteins, including P-gp and MRP1. Luciferase assay showed that circPVT1 acted as a sponge of miR-30a-5p, and Frizzled3 (FZD3) was a downstream target of miR-30a-5p. The enhanced 5-FU chemosensitivity by circPVT1 knockdown was reversed with miR-30a-5p inhibitor. Besides, the increased 5-FU chemosensitivity by miR-30a-5p mimics was reversed with FZD3 overexpression. Furthermore, knockdown of circPVT1 increased ferroptosis through downregulating p-ß-catenin, GPX4, and SLC7A11 while miR-30a-5p inhibition and FZD3 overexpression reversed the phenotype by upregulating p-ß-catenin, GPX4, and SLC7A11. CONCLUSIONS: These results suggested a key role for circPVT1 in ESCC 5-FU-chemosensitivity in regulating the Wnt/ß-catenin pathway and ferroptosis via miR-30a-5p/FZD3 axis, which might be a potential target in ESCC therapy.

Epigenetic Regulator KDM4D Restricts Tumorigenesis via Modulating SYVN1/HMGB1 Ubiquitination Axis in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Increasing researches have been reported that epigenetic alterations play critical roles in ESCC development. However, the role of the histone demethylase KDM4D in ESCC tumorigenesis is poorly investigated. This study aims to discover the underlying mechanisms between KDM4D and ESCC progression. METHODS: CCK-8 assays, clone formation assay and soft-agar assays were performed to assess cell proliferation. Transwell assay was utilized to assess cell migration efficiency, while sphere formation assay was used to evaluate the cell self-renewal ability. Bioinformatic analysis was conducted to identify prognostic factors and predict the potential E3 ubiquitin ligases. In vitro ubiquitination assay was conducted to confirm the regulations between SYVN1 and HMGB1. The mRNA levels or protein levels of genes were detected by real-time PCR and western blot analysis. In vivo tumor xenograft models were used to determine whether the HMGB1 inhibition affected the malignant features of ESCC cells. RESULT: Epigenome screening and low-throughput validations highlighted that KDM4D is a tumor suppressor in ESCC. KDM4D expressed lowly in tumors that predicts poor prognosis. KDM4D deficiency significantly enhanced tumor growth, migration and stemness. Mechanistically, KDM4D transcriptionally activates SYVN1 expressions via H3K9me3 demethylation at the promoter region, thereby triggering the ubiquitin-dependent degradation of HMGB1. Low KDM4D depended on accumulated HMGB1 to drive ESCC progression and aggressiveness. Targeting HMGB1 (Glycyrrhizin) could remarkably suppress ESCC tumor growth in vitro and in vivo, especially in KDM4D-deficient cells. CONCLUSIONS: We systematically identified KDM4D/SYVN1/HMGB1 axis in ESCC progression, proving novel biomarkers and potential therapeutic targets.

RELT promotes the growth of esophageal squamous cell carcinoma by activating the NF-κB pathway.

The members of the tumor necrosis factor receptor (TNFR) family have been demonstrated to play critical roles in various cancers. However, little is known about the function of the Receptor Expressed in Lymphoid Tissues (RELT) in cancers, which is a member of the TNFR family, especially in the esophageal squamous cell carcinoma (ESCC). In this study, we found that RELT expression was increased in ESCC tissues and was consequently associated with poor overall survival of ESCC patients. Moreover, RELT overexpression was found to promote cell growth, cell cycle progression, and suppressed cell apoptosis in vitro; it also decreased the expression of p27 and caspase 3, and increased the expression of survivin. In addition, RELT contributed to the tumorigenesis of ESCC in vivo. Furthermore, we suggest that RELT may function in the pathogenesis of ESCC by activating the nuclear factor κB (NF-κB) pathway. An inhibitor of NF-κB reversed the RELT-induced malignancy in the ESCC cells. Altogether, our findings identified that RELT served as an oncogene in ESCC through the NF-κB pathway, suggesting that RELT may be developed as a novel biomarker for the diagnosis and treatment of the ESCC.

MicroRNA­129 plays a protective role in sepsis­induced acute lung injury through the suppression of pulmonary inflammation via the modulation of the TAK1/NF­κB pathway.

Excessive inflammatory response and apoptosis play key roles in the pathogenic mechanisms of sepsis­induced acute lung injury (ALI); however, the molecular pathways linked to ALI pathogenesis remain unclear. Recently, microRNAs (miRNAs/miRs) have emerged as important regulators of inflammation and apoptosis in sepsis­induced ALI; however, the exact regulatory mechanisms of miRNAs remain poorly understood. In the present study, the gene microarray dataset GSE133733 obtained from the Gene Expression Omnibus database was analyzed and a total of 38 differentially regulated miRNAs were identified, including 17 upregulated miRNAs and 21 downregulated miRNAs, in mice with lipopolysaccharide (LPS)­induced ALI, in comparison to the normal control mice. miR­129 was found to be the most significant miRNA, among the identified miRNAs. The upregulation of miR­129 markedly alleviated LPS­induced lung injury, as indicated by the decrease in lung permeability in and the wet­to­dry lung weight ratio, as well as the improved survival rate of mice with ALI administered miR­129 mimic. Moreover, the upregulation of miR­129 reduced pulmonary inflammation and apoptosis in mice with ALI. Of note, transforming growth factor activated kinase­1 (TAK1), a well­known regulator of the nuclear factor­κB (NF­κB) pathway, was directly targeted by miR­129 in RAW 264.7 cells. More importantly, miR­129 upregulation impeded the LPS­induced activation of the TAK1/NF­κB signaling pathway, as illustrated by the suppression of the nuclear phosphorylated­p65, p­IκB­α and p­IKKß expression levels. Collectively, the findings of the present study indicate that miR­129 protects mice against sepsis­induced ALI by suppressing pulmonary inflammation and apoptosis through the regulation of the TAK1/NF­κB signaling pathway. This introduces the basis for future research concerning the application of miR­129 and its targets for the treatment of ALI.

MicroRNA-2053 involves in the progression of esophageal cancer by targeting KIF3C.

This study aimed to explore the role of micorRNA-2053 in esophageal cancer development. The expression level of miR-2053 in esophageal cancer cell lines was detected. After cell transfection, the effects of miR-2053 overexpression on proliferation, apoptosis, migration and invasion of esophageal cancer cells were determined. Moreover, the potential molecular mechanism was explored by measuring the epithelial-mesenchymal transition (EMT) and apoptosis-related proteins. Luciferase reporter assay was conducted to investigate the target gene of miR-2053. The protein expressions of PI3K/AKT pathway associated factors were detected after overexpression of miR-2053 or administration with the pathway inhibitor LY294002. The miR-2053 was downregulated in esophageal cancer cell lines. Overexpression of miR-2053 inhibited cell proliferation, migration and invasion while promoted apoptosis. Molecular mechanism elucidated that miR-2053 could reduce EMT and elevate the expression of pro-apoptotic proteins. Further study found that overexpressed miR-2053 could negatively regulate KIF3C and involve in PI3K/AKT signaling pathway. Our study demonstrated the downregulation of miR-2053 in esophageal cancer. Downregulation of miR-2053 involved in the proliferation, apoptosis, migration and invasion of esophageal cancer cells through upregulating KIF3C expression and activating the PI3K/AKT signaling pathway. miR-2053 may have the potential in clinical treatment of esophageal cancer.

Lotus leaf flavonoids induce apoptosis of human lung cancer A549 cells through the ROS/p38 MAPK pathway.

BACKGROUND: Leaves of the natural plant lotus are used in traditional Chinese medicine and tea production. They are rich in flavonoids. METHODS: In this study, lotus leaf flavonoids (LLF) were applied to human lung cancer A549 cells and human small cell lung cancer cells H446 in vitro to verify the effect of LLF on apoptosis in these cells through the ROS/p38 MAPK pathway. RESULTS: LLF had no toxic effect on normal cells at concentrations up to 500 µg/mL, but could significantly inhibit the proliferation of A549 cells and H446 cells. Flow cytometry showed that LLF could induce growth in A549 cells. We also found that LLF could increase ROS and MDA levels, and decrease SOD activity in A549 cells. Furthermore, qRT-PCR and western blot analyses showed that LLF could upregulate the expression of p38 MAPK (p-p38 MAPK), caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9 and Bax and downregulate the expression of Cu/Zn SOD, CAT, Nrf2, NQO1, HO-1, and Bcl-2 in A549 cells. Results of HPLC showed that LLF mainly contain five active substances: kaempferitrin, hyperoside, astragalin, phloridzin, and quercetin. The apoptosis-inducing effect of LLF on A549 cells came from these naturally active compounds. CONCLUSIONS: We have shown in this study that LLF is a bioactive substance that can induce apoptosis in A549 cells in vitro, and merits further research and development.

Lotus leaf flavonoids induce apoptosis of human lung cancer A549 cells through the ROS/p38 MAPK pathway

BACKGROUND: Leaves of the natural plant lotus are used in traditional Chinese medicine and tea production. They are rich in flavonoids. METHODS: In this study, lotus leaf flavonoids (LLF) were applied to human lung cancer A549 cells and human small cell lung cancer cells H446 in vitro to verify the effect of LLF on apoptosis in these cells through the ROS/p38 MAPK pathway. RESULTS: LLF had no toxic effect on normal cells at concentrations up to 500 µg/mL, but could significantly inhibit the proliferation of A549 cells and H446 cells. Flow cytometry showed that LLF could induce growth in A549 cells. We also found that LLF could increase ROS and MDA levels, and decrease SOD activity in A549 cells. Furthermore, qRT-PCR and western blot analyses showed that LLF could upregulate the expression of p38 MAPK (p-p38 MAPK), caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9 and Bax and downregulate the expression of Cu/Zn SOD, CAT, Nrf2, NQO1, HO-1, and Bcl-2 in A549 cells. Results of HPLC showed that LLF mainly contain five active substances: kaemp-feritrin, hyperoside, astragalin, phloridzin, and quercetin. The apoptosis-inducing effect of LLF on A549 cells came from these naturally active compounds. CONCLUSIONS: We have shown in this study that LLF is a bioactive substance that can induce apoptosis in A549 cells in vitro, and merits further research and development.

Effect of Malus asiatica Nakai Leaf Flavonoids on the Prevention of Esophageal Cancer in C57BL/6J Mice by Regulating the IL-17 Signaling Pathway.

BACKGROUND: The aim of this study was to observe the preventive effect of flavonoids extracted from Malus asiatica Nakai leaves (FMANL) on esophageal cancer in mice, especially the ability of FMANL to regulate the interleukin 17 (IL-17) signaling pathway during this process. MATERIALS AND METHODS: The C57BL/6J mice were treated with 4-nitroquinoline N-oxide (4NQO) to induce esophageal cancer, and the visceral tissue index and the serum and esophageal tissue indexes of mice were used to verify the effect of FMANL. RESULTS: The experimental results showed that FMANL can effectively control the changes in visceral tissue caused by esophageal cancer. FMANL could increase the cytokine levels of interleukin 10 (IL-10), monocyte chemotactic protein 1 (MCP-1) and decrease the cytokine levels of tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), interleukin 6 (IL-6), and interleukin 12p70 (IL-12p70) in serum of mice with esophageal cancer. FMANL could also reduce CD3+, CD4+, and CD8+ and enhance CD19+ mouse peripheral blood lymphocytes. The results of qPCR and Western blot analysis showed that FMANL could down-regulate the mRNA and protein expression levels of IL-17, interleukin 23 (IL-23), interleukin 1 beta (IL-1ß), chemokine (C-X-C) ligand 1 (CXCL1), chemokine (C-X-C) ligand 2 (CXCL2), S100 calcium-binding protein A8 (S100A8), S100 calcium-binding protein A9 (S100A9), matrix metalloprotein 9 (MMP-9), and matrix metalloprotein 13 (MMP-1) in mice with esophageal cancer. High-performance liquid chromatography (HPLC) detection showed that FMANL contained 10 chemicals, including rutin, hyperoside, isoquercitrin, dihydroquercetin, quercitrin, hesperidin, myricetin, baicalin, neohesperidin dihydrochalcone, and quercetin. CONCLUSION: It could be concluded that FMANL can effectively prevent experimentally induced esophageal cancer in mice, and its effects might be obtained from 10 compounds present in FMANL.

MicroRNA­212 facilitates the motility and invasiveness of esophageal squamous carcinoma cells.

As a tumor­associated microRNA (miR), miR­212 has dual functions; either as an oncogene or a tumor suppressor. A high expression level of miR­212 was reported to be associated with poor outcome in patients with esophageal squamous cell carcinoma (ESCC), however, its role in ESCC progression has not been explored. In the present study, an in vitro cell model of lentivirus­mediated gain­of­function demonstrated promotion of ESCC cell migration and invasion when miR­212 was overexpressed, and no effect on cell proliferation. miR­212 resulted in downregulation of the expression of E­cadherin, ß­catenin, vimentin and Twist1. Moreover, it led to increased levels of extracellular matrix (ECM)­degrading enzymes, matrix metalloproteinase­9 and urokinase­type plasminogen activator. Furthermore, berberine inhibited miR­212­induced ESCC cell migration, unlike the PI3K inhibitor LY294002, rapamycin (mTOR inhibitor), 5­(Tetradecyloxy)­2­furoic acid (TOFA; an acetyl­CoA carboxylase 1 inhibitor), metformin and propranolol. These data suggest that miR­212 activates multiple signaling cascades and facilitates ESCC cell motility and invasion by promoting the epithelial­mesenchymal transition and degrading the ECM. Berberine may be a potential therapeutic agent against metastasis in patients with ESCC, who express high levels of miR­212.

Berberine displays antitumor activity in esophageal cancer cells in vitro.

AIM: To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms. METHODS: Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD ModFit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting. RESULTS: Berberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 µmol/L berberine for 48 h, the number of cells in G2/M phase (25.94% ± 5.01%) was significantly higher than that in the control group (9.77% ± 1.28%, P < 0.01), and berberine treatment resulted in p21 up-regulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h post-treatment, when compared with control cells (0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner. CONCLUSION: Berberine is an inhibitor of human EC cell growth and could be considered as a potential drug for the treatment of EC patients.

Upregulation of MALAT-1 and its association with survival rate and the effect on cell cycle and migration in patients with esophageal squamous cell carcinoma.

The aim of this study is to investigate whether metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) can be used as a potential therapy target for human esophageal squamous cell carcinoma. MALAT-1 expression levels were detected in 137 paired EC samples and adjacent nonneoplastic tissues. Human esophageal carcinoma cell lines EC9706 and KYSE150 were transfected with MALAT-1 small interference RNA. Cell proliferation, migration/invasion ability, cell cycle, and apoptosis were assessed. MALAT-1 expressed higher levels in esophageal cancer tissues when compared with paired adjacent normal tissues. This high expression was associated with a decreased survival rate. MALAT-1 knockdown induced a decrease in proliferation-enhanced apoptosis, inhibited migration/invasion, and reduced colony formation and led to cell cycle arrest at the G2/M phase. These data indicates that MALAT-1 could be exploited for therapeutic benefit.

Expression of long non-coding RNA ZEB1-AS1 in esophageal squamous cell carcinoma and its correlation with tumor progression and patient survival.

BACKGROUND: LncRNA ZEB1-AS1 has been identified as a tumor oncogene in hepatocellular carcinoma. However, the clinical significance in esophageal squamous cell carcinoma (ESCC) is still unknown. The aim of this study was to explore ZEB1-AS1 expression levels and evaluated its clinical significance in ESCC patients. METHODS: LNCRNA ZEB1-AS1 expression was determined by quantitative real-time PCR (QRT-PCR) in 87 pairs of ESCC specimens and adjacent non-tumor tissues. Then, the association of ZEB1-AS1 expression with clinicopathological factors or survival of ESCC patients were determined. RESULTS: LNCRNA ZEB1-AS1 was found up-regulated in ESCC tissues compared to adjacent non-tumor tissues. Increased lncRNA ZEB1-AS1 expression was significantly associated with tumor grade, depth of invasion, and lymph node metastasis. Kaplan-Meier analysis revealed that ESCC patients with high ZEB1-AS1 expression had a poorer overall survival and disease-free survival. Furthermore, multivariate analysis suggested that ZEB1-AS1 expression was identified as an independent prognostic factor in patients with ESCC. CONCLUSION: These results indicated that lncRNA ZEB1-AS1 was associated with tumor progression and could be an independent prognostic factor for ESCC patients.