RNF152 Suppresses Fatty Acid Oxidation and Metastasis of Lung Adenocarcinoma by Inhibiting IRAK1-Mediated AKR1B10 Expression.

Lung adenocarcinoma (LUAD) is a common subtype of primary lung cancer. Fatty acid oxidation plays a key role in LUAD development by providing energy for tumor cells. This study aimed to identify the role of ring finger protein 152 (RNF152) in LUAD. RNF152 was down-regulated in LUAD, and low RNF152 expression correlated with a poor prognosis in LUAD patients. RNF152 overexpression inhibited the proliferation and malignant phenotype of LUAD cells, whereas RNF152 knockdown exerted an opposite effect. Tumor cells overexpressing RNF152 showed less fatty acid oxidation compared with control cells, whereas RNF152 knockdown induced fatty acid uptake and oxidation. Further analysis revealed the binding reaction between RNF152 and interleukin-1 receptor-associated kinase 1 (IRAK1). RNF152 reduced the stability of IRAK1 in LUAD cells by promoting its ubiquitination. RNF152-overexpressed tumor cells exhibited a significantly lower level of Aldo-Keto reductase family 1 member 10 (AKR1B10), whereas up-regulation of IRAK1 restored the expression of AKR1B10 in RNF152-overexpressed cells. Furthermore, up-regulation of IRAK1 eliminated the antitumor effect of RNF152 in LUAD cells. Mouse xenograft models confirmed the inhibitory effect of RNF152 on the tumorigenesis and metastasis of LUAD. Taken together, RNF152 played a tumor suppressive role in LUAD by promoting IRAK1 ubiquitination and IRAK1-mediated down-regulation of AKR1B10, thereby reversing the malignant phenotype of LUAD.

Silencing of histone deacetylase 3 suppresses the development of esophageal squamous cell carcinoma through regulation of miR-494-mediated TGIF1.

BACKGROUND: Deacetylation of histones by histone deacetylase 3 (HDAC3) acts importantly in modulating apoptosis, DNA damage and cellular progression. Herein, we aimed to unravel the functional role of HDAC3 in a lethal disease, esophageal squamous cell carcinoma (ESCC). METHODS: The expression of HDAC3 in clinically collected ESCC tissues was determined by RT-qPCR and immunohistochemistry. As revealed from bioinformatics analysis, the putative relations between HDAC3 and microRNA-494 (miR-494) and between miR-494 and transforming growth factor beta (TGFß)-inducing factor 1 (TGIF1) were further verified by chromatin immunoprecipitation and dual-luciferase reporter gene assay. Functional roles of shRNA-mediated depletion of HDAC3, miR-494 mimic and overexpressed TGIF1 were explored by gain- and loss-of-function assays with regard to ESCC cell biological behaviors. A nude mouse model of ESCC was developed for in vivo validation. RESULTS: HDAC3 was highly expressed in ESCC tissues, suggestive of poor prognosis while TGIF1 was upregulated and miR-494 was downregulated. Mechanistic investigation revealed that HDAC3 inhibited miR-494 expression and TGIF1 was a direct target of miR-494. Furthermore, silencing HDAC3 or overexpressing miR-494 was demonstrated to suppress aggressive phenotypes of ESCC cells both in vitro through the activated TGFß signaling pathway and in vivo, while TGIF1 overexpression induced opposite results. CONCLUSION: Collectively, our findings provided demonstration regarding the oncogenic property of HDAC3 in ESCC via the miR-494/TGIF1/TGFß axis.

CircTUBGCP3 facilitates the tumorigenesis of lung adenocarcinoma by sponging miR-885-3p.

BACKGROUND: Circular RNAs (circRNAs) act pivotal roles in the progression of multiple malignancies. However, the underlying mechanisms by which hsa_circ_0007031 (circTUBGCP3) contributes to lung adenocarcinoma (LAC) remain largely unknown. METHODS: The association of circTUBGCP3 expression with clinicopathological characteristics and prognosis in patients with LAC was determined by RT-qPCR and fluorescence in situ hybridization. The in vitro functional experiments as well as a subcutaneous tumorigenesis model were executed to estimate the role of circTUBGCP3 in LAC cells. The interaction between circTUBGCP3 and miR-885-3p was confirmed by RNA immunoprecipitation, luciferase gene report and RT-qPCR assays. The effects of circTUBGCP3 on miR-885-3p-mediated Wnt10b/ß-catenin signaling were evaluated by Western blot. RESULTS: The upregulation of circTUBGCP3 or downregulation of miR-885-3p was associated with the pathological stage and poor survival in patients with LAC. Restored expression of circTUBGCP3 facilitated the growth and invasion of LAC cells, but knockdown of circTUBGCP3 harbored the opposite effects. In mechanism, circTUBGCP3 could act as a sponge of miR-885-3p, which suppressed the cell proliferation and colony formation and attenuated the tumor-promoting effects of circTUBGCP3. Wnt10b as a target of miR-885-3p could be upregulated be circTUBGCP3 and indicate poor survival in patient with LAC. CONCLUSIONS: Our findings demonstrated that circTUBGCP3 promoted LAC progression by sponging miR-885-3p, and might represent a prognostic factor for LAC.

PAR1 and PAR4 exert opposite effects on tumor growth and metastasis of esophageal squamous cell carcinoma via STAT3 and NF-κB signaling pathways.

BACKGROUND: Esophageal carcinogenesis is a multifactorial process in which genetic and environmental factors interact to activate intracellular signals, leading to the uncontrolled survival and growth of esophageal squamous cell carcinoma (ESCC) cells. The intracellular pathways of ESCC cells could be regulated by proteinase activated-receptors (PARs), which are comprised of four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4). Therefore, the function and possible mechanism of PAR1 and PAR4 in the progression of ECSS were explored in our study. METHODS: First, we detected the expression levels of PAR1 and PAR4 in 27 cases of ESCC specimens and cell lines by RT-qPCR, IHC and western blot. Meanwhile, the correlation between PAR1/PAR4 expression levels, clinicopathological characteristics, and disease free survival was analyzed. Then, we constructed PAR1/PAR4 knockdown cell models and investigated the role of PAR1/PAR4 knockdown on the proliferation, apoptosis, changes of calcium flow, and metastasis of ESCC cells via MTT, flow cytometry, transwell and wound healing assays in vitro. Further, an experimental metastasis model in vivo was established to explore the role of stable PAR1/PAR4 knockdown on the growth and metastasis of ESCC cells. Finally, the role of nSMase2 in the activation of NF-κB induced by PAR4 and the role of NF-κB and STAT3 signaling pathways in the PAR1/PAR4-mediated tumor promoting or suppressive functions were measured by immunoprecipitation, western blot and immunofluorescence assays. RESULTS: First, the integrated results demonstrated the expression levels of PAR1 and PAR4 are inversely proportional in ESCC. PAR1 potently enhanced tumor growth and metastasis, while PAR4 had an inhibitory effect. Further, the co-activation of STAT3 and NF-κB was involved in the PAR1 activation-induced tumor promoting effect, while only NF-κB participated in the PAR4 activation-induced tumor inhibitory effect in ESCC. To be specific, FAK/PI3K/AKT/STAT3/NF-κB signaling mediated PAR1 activation-induced tumor promoting effect and nSMase2/MAPK/NF-κB signaling mediated PAR4 activation-induced tumor inhibitory effect. CONCLUSIONS: Overall, the study has provided new insights into the potential implication of PAR1 and PAR4 in the pathogenesis of ESCC. Besides, FAK/PI3K/AKT/STAT3/NF-κB and nSMase2/MAPK/NF-κB pathways may be novel targets for regulating tumor growth and metastasis in ESCC patients.

microRNA-10b confers cisplatin resistance by activating AKT/mTOR/P70S6K signaling via targeting PPARγ in esophageal cancer.

It is well known that the acquisition of chemoresistance is a major obstacle for the effective treatment of human cancers. It is reported that microRNAs (miRNAs) are implicated in chemotherapy resistance of various malignancies. miR-10b was previously proved as an oncogene in multiple malignancies, including esophageal cancer. However, its biological significance in regulating cisplatin (DDP) resistance in esophageal cancer is still elusive. Here, we observed that miR-10b expression was upregulated and peroxisome proliferator-activated receptor-γ (PPARγ) expression was downregulated in esophageal cancer tumor tissues and cells. PPARγ was proved as a functional target of miR-10b. Moreover, suppression of miR-10b enhanced the chemosensitivity of esophageal cancer cells to DDP in vitro and in vivo. In addition, PPARγ-mediated DDP sensitivity was weakened by miR-10b overexpression. Furthermore, miR-10b-activated AKT/mTOR/p70S6K signaling pathway through targeting PPARγ. Inactivation of AKT/mTOR/p70S6K by AKT inhibitor (GSK690693) attenuated miR-10b-induced DDP resistance in esophageal cancer cells. Taken together these observation, miRNA-10b-mediated PPARγ inhibition enhanced DDP resistance by activating the AKT/mTOR/P70S6K signaling in esophageal cancer, suggesting a potential target to improve therapeutic response of patients with esophageal cancer to DDP.

Long noncoding RNA ADAMTS9-AS2 suppresses the progression of esophageal cancer by mediating CDH3 promoter methylation.

Long noncoding RNAs (lncRNAs) have been implicated in the biology of esophageal cancer via mRNA degradation or translational inhibition. CDH3 is also aberrantly expressed in numerous cancers. This study was conducted with the hypothesis that ADAMTS9-AS2 or CDH3 methylation plays a role in esophageal cancer cell activity and in vivo development. Firstly, mRNA levels of ADAMTS9-AS2 and CDH3 in esophageal cancer tissues and cells were detected by reverse-transcription quantitative polymerase chain reaction. Afterward, esophageal cancer OE21 cells were treated with overexpression of ADAMTS9-AS2, siRNA against ADAMTS9-AS2, overexpression of CDH3 and demethylating agent 5-aza-dc. The biological functions of esophageal cancer OE21 cells were assayed to define the regulatory mechanisms of ADAMTS9-AS2 in esophageal cancer. The interactions among ADAMTS9-AS2, DNMT1/DNMT3 (A/B) and CDH3 were detected by MSP, RNA pull-down, RIP, and ChIP assays. The in vitro findings were reproduced in nude mice to explore the role of ADAMTS9-AS2 in the development of esophageal cancer in vivo. Esophageal cancers expressed low levels of ADAMTS9-AS2 and high levels of CDH3. Methylation of CDH3 promoter was induced by ADAMTS9-AS2 via DNMT1/DNMT3 (A/B). Furthermore, proliferation, invasion, and migration of esophageal cancer cells were inhibited by ADAMTS9-AS2 via downregulation of CDH3. Suppressed esophageal cancer development in vivo was also detected after ADAMTS9-AS2 overexpression. Overexpressed ADAMTS9-AS2 aids in the suppression of esophageal cancer development, which is achieved via inducing CDH3 promoter methylation.

Upregulation of long noncoding RNA SPRY4-IT1 promotes metastasis of esophageal squamous cell carcinoma via induction of epithelial-mesenchymal transition.

Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. In the present study, we find that the expression of lncRNA SPRY4-IT1 is significantly upregulated in ESCC cell lines as compared with human esophageal epithelial cell line HEEC. Overexpression of SPRY4-IT1 can increase in vitro motility of ESCC cells via induction of epithelial-mesenchymal transition (EMT), which is characterized by increasing the expression of vimentin (Vim) and fibronectin (FN) with a concomitant decrease of E-cadherin (E-Cad) and ZO-1, while silencing of SPRY4-IT1 significantly inhibits the in vitro motility of ESCC cells. Further, the knockdown of SPRY4-IT1 also significantly attenuates TFG-ß-induced EMT of ESCC cells. Further, lncRNA SPRY4-IT1 can directly increase the transcription, expression, and nuclear localization of Snail, one key transcription factor during the EMT processes of cancer cells, while siRNA-mediated specific knockdown of Snail can significantly attenuate SPRY4-IT1-induced EMT of ESCC cells. Our results suggest that lncRNA SPRY4-IT1 might be considered as a novel oncogene involved in ESCC progression.

LncRNA Rian ameliorates sevoflurane anesthesia-induced cognitive dysfunction through regulation of miR-143-3p/LIMK1 axis.

Sevoflurane could stimulate neurotoxicity and result in postoperative cognitive dysfunction (POCD). Long non-coding RNAs (lncRNAs) have been implicated in the regulation of nervous system disease. This study was performed to investigate role and mechanism of lncRNA Rian (RNA imprinted and accumulated in nucleus) in sevoflurane anesthesia-induced cognitive dysfunction. Mice post-sevoflurane anesthesia showed cognitive impairments and neuronal damage and apoptosis. However, intracerebroventricularly injection with Adenovirus (Ad) for the over-expression of Rian ameliorated sevoflurane-induced neuronal damage and apoptosis. Cognitive impairments induced by sevoflurane were attenuated by injection with Ad-Rian. Moreover, transfection with Ad-Rian also protected isolated primary hippocampal neurons against sevoflurane-induced decrease of cell viability and increase of lactic acid dehydrogenase (LDH) and apoptosis. Mechanistically, Rian bind to miR-143-3p, and decreased expression of LIMK1 (Lim kinase 1) through negative regulation of miR-143-3p. Knockdown of LIMK1 aggravated sevoflurane-induced decrease of cell viability and increase of LDH and apoptosis in neurons, while over-expression attenuated LIMK1 silence-induced neuronal damage post-sevoflurane anesthesia. In conclusion, Rian demonstrated neuroprotective effects against sevoflurane anesthesia-induced cognitive dysfunction through regulation of miR-143-3p/LIMK1 axis, providing promising target for sevoflurane anesthesia-induced cognitive dysfunction.

McKeown or Ivor Lewis minimally invasive esophagectomy: a systematic review and meta-analysis.

BACKGROUND: Minimally invasive esophagectomy (MIE) is increasingly accepted in many countries. McKeown esophagectomy and Ivor Lewis esophagectomy are two protocols commonly used for MIE, but which one provides more benefit to the patients remains matter of controversy. METHODS: All records in PubMed, Embase, Medline, The Cochrane Library, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Chinese VIP Information till May 2019 were systematically retrieved to compare the cohort studies of McKeown esophagectomy and Ivor Lewis esophagectomy. A meta-analysis of the extracted data was performed using the Review Manager 5.3 and Stata 15 software. RESULTS: The meta-analysis included 23 cohort studies in which a total of 4,933 patients were enrolled. The results revealed that minimally invasive McKeown esophagectomy (MIME) was superior to minimally invasive Ivor Lewis esophagectomy (MILE) in hospital cost, but inferior to it in operating time, length of hospital stay, in-hospital mortality, 30-day mortality, 90-day mortality, anastomotic leakage, anastomotic leakage requiring surgery, anastomotic stenosis, recurrent laryngeal nerve (RLN) injury, chylothorax, pulmonary complications and total complications. There were no statistical differences between MIME and MILE in blood loss, detected number of lymph nodes, blood transfusion rate, R0 resection rate, re-operation rate, drainage duration, length of the stay in intensive care unit (ICU), 1-year mortality, lung infection, cardiac arrhythmia and delayed gastric emptying. CONCLUSIONS: Except for the cost, MILE is superior to MIME in several aspects, and may represent a better choice for MIE. The results of the present study should be interpreted with caution since the meta-analysis is based on nonrandom cohort studies which may have a selection bias.

MicroRNA let-7i Inhibits Histone Lysine Demethylase KDM5B to Halt Esophageal Cancer Progression.

Recent studies have suggested that microRNA let-7i is a tumor suppressor in human cancers, including esophageal cancer, but its underlying mechanism is not yet fully understood. We investigated the role and mechanisms of let-7i in the progression of esophageal cancer. We first showed that let-7i was downregulated in esophageal cancer tissues and cells and then linked its low expression to cancer progression. Bioinformatic analysis predicted KDM5B as a target gene of let-7i, which was confirmed by a dual-luciferase reporter assay. Loss- and gain-of function approaches were adopted to examine the interactions of let-7i, KDM5B, SOX17, and GREB1 in vitro and in vivo. Overexpression of let-7i suppressed esophageal cancer cell proliferation and invasion and promoted apoptosis. Mechanistic investigation showed that let-7i targeted and inhibited KDM5B expression, whereas KDM5B enhanced H3K4me3 at the SOX17 promoter region. Overexpression of let-7i suppressed the expression of GREB1 in esophageal cancer cells by regulating the KDM5B/SOX17 axis in vivo and in vitro. Taken together, our findings reveal the tumor-suppressive properties of let-7i in esophageal cancer in association with an apparent KDM5B-dependent SOX17/GREB1 axis. This study offers a potential prognostic marker and therapeutic target for esophageal cancer.

Structure, Function, Diversity, and Composition of Fungal Communities in Rhizospheric Soil of Coptis chinensis Franch under a Successive Cropping System.

Soil types and cropping systems influence the diversity and composition of the rhizospheric microbial communities. Coptis chinensis Franch is one of the most important medicinal plants in China. In the current study, we provide detailed information regarding the diversity and composition of rhizospheric fungal communities of the C. chinensis plants in continuous cropping fields and fallow fields in two seasons (winter and summer), using next-generation sequencing. Alpha diversity was higher in the five-year C. chinensis field and lower in fallow fields. Significant differences analysis confirmed more fungi in the cultivated field soil than in fallow fields. Additionally, PCoA of beta diversity indices revealed that samples associated with the cultivated fields and fallow fields in different seasons were separated. Five fungal phyla (Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota and Mucoromycota) were identified from the soil samples in addition to the unclassified fungal taxa and Cryptomycota, and among these phyla, Ascomycota was predominantly found. FUNGuild fungal functional prediction revealed that saprotroph was the dominant trophic type in all two time-series soil samples. Redundancy analysis (RDA) of the dominant phyla data and soil physiochemical properties revealed the variations in fungal community structure in the soil samples. Knowledge from the present study could provide a valuable reference for solving the continuous cropping problems and promote the sustainable development of the C. chinensis industry.

LINC00152 facilitates tumorigenesis in esophageal squamous cell carcinoma via miR-153-3p/FYN axis.

Long non-coding RNAs (LncRNAs) have been found to be associated with the biological behaviors of human cancers. LINC00152 is reported as an oncogene in many kinds of malignancies. However, the functions and mechanisms of LINC00152 involved in esophageal squamous cell carcinoma (ESCC) remain elusive. Our results revealed that LINC00152 expression was up-regulated in ESCC, and correlated with advanced TNM stage, lymph node metastasis, and poor prognosis of ESCC patients. Functionally, LINC00152 knockdown suppressed proliferation, decreased colony forming ability, and induced apoptosis in ESCC cells. Mechanically, LINC00152 functioned as a competing endogenous RNA (ceRNA) to sponge miR-153-3p, thereby facilitating its downstream target FYN. Moreover, miR-153-3p-mediated tumor-suppressive effects were partly reversed following LINC00152 overexpression. Also, FYN knockdown displayed a similar anti-cancerous role in ESCC cells. Taken together, LINC00152 contributed to ESCC progression by down-regulating miR-153-3p and promoting FYN expression, uncovering a novel LINC00152/miR-153-3p/FYN regulatory pathway in ESCC.

SNHG14 confers gefitinib resistance in non-small cell lung cancer by up-regulating ABCB1 via sponging miR-206-3p.

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been widely used as a first-line agent in EGFR-mutant non-small cell lung cancer (NSCLC). Nevertheless, the development of chemoresistance ultimately limited the curative effect of anti-cancer drugs. The present study aims to investigate the functions of SNHG14 in gefitinib resistance and gain insight into the underlying molecular mechanisms. In the present study, we found that SNHG14 expression was elevated and miR-206-3p expression was decreased in gefitinib-resistant NSCLC tumor tissues and cells. Functionally, SNHG14 overexpression increased gefitinib resistance by promoting cell viability, lowering apoptosis and enhancing colony forming ability, while SNHG14 knockdown reduced gefitinib resistance in NSCLC cells. Mechanistically, SNHG14 induced ABCB1 expression via interaction with miR-206-3p. Moreover, depletion of SNHG14 enhanced the sensitivity of NSCLC cells to gefitinib in vivo. Together, SNHG14 confers gefitinib resistance in NSCLC by regulating miR-206-3p/ABCB1 pathway, contributing to a better understanding of SNHG14 in acquired resistance and elucidating a candidate target to improve treatment response of NSCLC patients.

Long noncoding RNA PART1 promotes progression of non-small cell lung cancer cells via JAK-STAT signaling pathway.

Non-small cell lung cancer (NSCLC), the major type of lung cancer, becomes the greatest threat to the life of people. Growing evidence shows prostate androgen-regulated transcript 1 (PART1) is considered as effective markers for prostate cancer, and has been shown to be associated with poor prognosis of NSCLC. However, the tumorigenic mechanism of PART1 in NSCLC remains to be investigated. In this study, we found that the expression of PART1 was robustly induced in NSCLC tissues and cell lines. Functional studies established that overexpression of PART1 could promote NSCLC cell proliferation, migration, and invasion, while interference of PART1 inhibited NSCLC progression. Our results also identified miR-635 as a novel target of PART1, whose expression was inhibited by PART1 in NSCLC cell lines. Moreover, gain- and loss-of-function studies revealed that PART1 could sponge miR-635 and increase the expression of Janus kinase (JAK) and signal transducer and activator of transcription proteins (STATs). Finally, we deciphered the molecular mechanism by which PART1 contributed to promotion of NSCLC cell progression via phosphorylation and activation of JAK-STAT signaling pathway. The animal experiment further confirmed that interference of NSCLC could suppress in vivo tumorigenic ability of NSCLC with favorable pharmacological activity via inactivation of JAK-STAT signaling pathway. In conclusion, our findings clarified the biologic significance of PART1/miR-635/JAK-STAT axis in NSCLC progression and provided novel evidence that PART1 may be a new potential therapeutic target for the treatment of NSCLC.

Long Non-coding RNA CASC2 Enhances the Antitumor Activity of Cisplatin Through Suppressing the Akt Pathway by Inhibition of miR-181a in Esophageal Squamous Cell Carcinoma Cells.

Background: Long non-coding RNA CASC2 (lncRNA CASC2) has been found to be down-regulated in esophageal squamous cell carcinoma (ESCC). However, the effect of CASC2 on cisplatin-treated ESCC was unclear. The present study aimed to evaluate the role of CASC2 in cisplatin-treated ESCC cells. Methods: The expression levels of CASC2 and miR-181a were detected by qRT-PCR. Cell viability was measured by MTT assay. The cytotoxicity effect was detected by lactate dehydrogenase (LDH) release assay. Cell apoptosis was tested by flow cytometry. The protein levels of protein kinase B (Akt) and p-Akt were detected by western blotting. Results: The results showed that CASC2 was low-expressed in ESCC cell lines. Overexpression of CASC2 enhanced the inhibitory effect of cisplatin on cell viability and promoted cisplatin-induced LDH release and apoptosis. We also found that miR-181a expression levels were increased in ESCC cell lines. MiR-181a inhibitor enhanced the antitumor activity of cisplatin, which was similar with the effect of CASC2. CASC2 directly interacted with miR-181a and inhibited the miR-181a expression. MiR-181a reversed the effects of CASC2 on antitumor activity of cisplatin. In addition, we also found that CASC2 suppressed the Akt pathway by inhibiting miR-181a. Conclusions: CASC2 promoted the antitumor activity of cisplatin through inhibiting Akt pathway via negatively regulating miR-181a in ESCC cells. The results provide a new insight for ESCC therapy.

Overexpressed PKMYT1 promotes tumor progression and associates with poor survival in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors worldwide and the 5-year overall survival rate remains poor. Protein kinase, membrane associated tyrosine/threonine (PKMYT1) is overexpressed in several cancers and participate in tumor progression. However, the mechanism of PKMYT1 in ESCC is unclear. PURPOSE: The objective of our study was to demonstrate the the expression and role of PKMYT1 in ESCC. PATIENTS AND METHODS:   We detected the expression of PKMYT1 in ESCC patients and analysed the correlation with overall survival time and disease-free survival time. Then we detected PKMYT1 expression in ESCC cell lines and immortalized human esophageal epithelial cell line. Down-regulated PKMYT1 was carried out in KYSE70 and KYSE450 cells to invetigate the mechanism of PKMYT1 in ESCC cells. RESULTS: PKMYT1 was up-regulated in tumor tissues and ESCC cell lines, and higher expression of PKMYT1 correlated with poorer overall survival in ESCC patients. Besides, in ESCC cell lines KYSE70 and KYSE450, knocking down PKMYT1 allowed more cells to skip G2/M checkpoint to complete mitosis, which promoted cell apoptosis, inhibited cell proliferation, and prevented the EMT phenotype in vitro. Meantime, we also observed that down-regulated PKMYT1 in ESCC cells suppressed AKT/mTOR signaling pathway. These results demonstrated PKMYT1 may act as an oncogene in ESCC. CONCLUSION: PKMYT1 plays an crutial role in ESCC progression, downregulated PKMYT1 might inhibit the development of ESCC by AKT/mTOR signaling pathway, and might be a novel target in the treatment of ESCC.

A new technology for reducing anastomotic fistula in the neck after esophageal cancer surgery.

BACKGROUND: To explore the risk factors and prevention methods of cervical mechanical anastomotic fistula and stenosis after the radical resection of esophageal cancer. METHODS: From March 2018 to November 2018, 128 patients undergoing mechanical anastomosis of esophageal cancer were selected from the Department of Thoracic Surgery of The First Affiliated Hospital of Zhengzhou University. All the enrolled patients were operated on using the Mckeown method, and a retrospective study was conducted. Data for preoperative and postoperative test indices, intraoperative embedding materials, postoperative complications, and preoperative and postoperative treatment were collected, and the relationship between various factors and the incidence of cervical anastomotic fistula and stenosis was analysed. Univariate analysis was conducted using t tests or Fisher's exact probability method, and multivariate analysis was conducted using logistic regression models. RESULTS: All 128 patients successfully underwent surgery without dying. The enrolled patients were evaluated using the Stooler classification, with 28 patients having grade 0, 41 patients having grade 1, 34 patients having grade 2, 21 patients having grade 3, and 4 patients having grade 4 stenosis. Patients with stenosis of grade 3 or above had obvious choking sensation, which could only be relieved by balloon dilation. Symptoms in all patients with stenosis were relieved by balloon dilation. There were no significant differences between the two groups regarding embedding materials, preoperative choking history, history of alcohol consumption, history of hypertension, history of coronary heart disease, history of diabetes, postoperative calcium concentration, average albumin concentration, average platelet concentration, body mass index, anastomotic fistula, preoperative chemotherapy, postoperative chemotherapy, or postoperative cough (P>0.05). There were significant differences in postoperative reflux (χ2=11.338, P<0.05) and scar constitution (χ2=12.497, P<0.05). The effects of embedding materials in patients with anastomotic fistula were significantly different (χ2=4.372, P<0.05). CONCLUSIONS: Postoperative reflux and scar constitution may be risk factors for postoperative anastomotic stenosis after resection of esophageal cancer. There was almost no difference in the effects on esophageal anastomotic stenosis between embedding materials and the omentum majus, but Neoveil® may have certain advantages in preventing cervical anastomotic fistula, and thus may have certain clinical application value.

Diagnostic value of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography for preoperative lymph node metastasis of esophageal cancer: A meta-analysis.

OBJECTIVE: We determined the value of F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) for the assessment of preoperative lymph node metastases in patients with esophageal cancer. METHODS: We searched electronic database indexes for articles on PET/CT assessment of lymph node status. Information including true positives, false positives, false negatives, and true negatives was obtained. Based on these data, the pooled sensitivity, specificity, diagnostic odds ratio, and likelihood ratio were calculated using bivariate models and receiver operating characteristic curves (ROCs) were drawn. RESULTS: Patients without neoadjuvant treatment had a pooled sensitivity and specificity (95% confidence interval [CI]) of 0.57 (0.45-0.69) and 0.91 (0.85-0.95), respectively. Patients who received neoadjuvant treatment had a pooled sensitivity and specificity of 0.53 (0.35-0.70) and 0.96 (0.86-0.99), respectively. CONCLUSIONS: The PET/CT has a high diagnostic specificity but its diagnostic sensitivity is low; thus, its diagnosis findings cannot accurately reflect the lymph node status.

Overexpression of calcyphosine is associated with poor prognosis in esophageal squamous cell carcinoma.

Calcyphosine (CAPS), a calcium-binding protein, has been identified as a potential diagnostic and prognostic biomarker in several human carcinomas. However, little is known about CAPS in esophageal squamous cell carcinoma (ESCC). The present study aimed to investigate the expression levels of CAPS in ESCC tissues and evaluate its clinicopathological significance. Reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining were conducted to detect the expression of CAPS in ESCC tissues and adjacent non-cancerous tissues. ESCC samples exhibited higher levels of CAPS mRNA than paired non-cancerous samples (P=0.0015), and the mRNA level of CAPS was positively associated with histological grade (P=0.0013) and tumor invasion depth (P=0.0206). In addition, Kaplan-Meier survival analysis revealed that patients with high CAPS expression experienced significantly shorter 5-year overall survival times than those with low CAPS expression (P=0.0112). Multivariate analysis demonstrated that CAPS protein expression was an independent prognostic biomarker for patients with ESCC. In conclusion, the findings of the present study demonstrated that CAPS may represent a novel diagnostic indicator and an independent prognostic biomarker in ESCC.