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Preclinical studies suggest lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression. We conducted a phase II randomized trial to test the effect of decreasing dietary fat combined with decreasing the dietary omega-6:omega-3 ratio on biomarkers related to prostate cancer development and progression. Patients undergoing radical prostatectomy were randomly assigned to receive a low-fat diet with 5 grams of fish oil daily (dietary omega-6:omega-3 ratio of 2:1) or a control Western diet (omega-6:omega-3 ratio of 15:1) for four to six weeks prior to surgery. The primary endpoint was change in serum insulin-like growth factor I (IGF-1) between arms. Secondary endpoints were serum IGFBP-1, prostate prostaglandin E2 levels, omega-6:omega-3 fatty acid ratios, COX-2, and markers of proliferation and apoptosis. Fifty-five patients were randomized and 48 completed the trial. There was no treatment difference in the primary outcome. Positive secondary outcomes in the low-fat fish oil versus Western group were reduced benign and malignant prostate tissue omega-6:omega-3 ratios, reduced proliferation (Ki-67 index), and reduced proliferation in an ex vivo bioassay when patient sera was applied to prostate cancer cells in vitro. In summary, four to six weeks of a low-fat diet and fish oil capsules to achieve an omega-6:omega-3 fatty acid ratio of 2:1 had no effect on serum IGF-1 levels, though in secondary analyses, the intervention resulted in decreased prostate cancer proliferation and decreased prostate tissue omega-6:omega-3 ratios. These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology. Cancer Prev Res; 4(12); 2062–71. ©2011 AACR.

Background: The ecology and evolution of phoretic mites and termites have not been well studied. In particular, it is unknown whether the specific relationship between mites and termites is commensal or parasitic. High phoretic mite densities have often been found to occur in weak termite colonies, suggesting that the relationship is closer to that of parasitism than commensalism. Results: To examine this, Coptotermes formosanus was used as a carrier, and Acarus farris as the phoretic mite. We used video recordings to observe termite social immunity behaviors and bioassay to examine termite fitness. Our results showed that the attachment of the mite on the termite can enhance termite social immunity behaviors like alarm vibration and grooming frequency while decreasing the duration of individual grooming episodes in phoretic mites. Further, A. farris phoresy led to a 22.91% reduction in termite abdomen volume and a 3.31-fold increase in termite mortality. Conclusions: Phoretic behavior hastened termites’ death, and helped propagate the population of mites feeding on dead termites. Frequent social behaviors may cost termites energy, and thus provides a case for phoresy being a precursor to parasitism. The specific relationship between A. farris and C. formosanus is closer to parasitism than to commensalism.

Background. The epithelial-mesenchymal transition (EMT) is a pivotal process for fibrotic disease, embryonic development, and wound healing. Moreover, some evidence has proven that the disorder of EMT also plays an important role in carcinogenesis, especially invasion and metastasis of various tumors (Ritchie et al., 2015). Additionally, gastric adenocarcinoma (GAC) is a common gastrointestinal malignancy which is the fourth most commonly diagnosed tumor. Our study is aimed at identifying the prognostic value of EMT-related genes in gastric adenocarcinoma. Methods. Firstly, high-throughput and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. 99 differentially expressed EMT-related genes (ERGs) were obtained in these gastric adenocarcinoma data. Secondly, GO and KEGG enrichment analyses show that EMT may promote gastric carcinogenesis. Next, 10 ERGs associated with prognosis of gastric adenocarcinoma patients are screened out by univariate Cox regression, and 6 pivotal prognostic ERGs (MMP8, MMP11, TFDP3, MYB, F2, and CNTN1) are identified through multivariate Cox regression. These 6 genes are confirmed with significant prognostic value in gastric adenocarcinoma through overall survival (OS) analysis. Finally, a risk score formula is constructed and tested in another gastric adenocarcinoma cohort from GEO. Results. 99 differentially expressed EMT-related genes (ERGs) and their enriched pathways are identified. 10 ERGs are strongly related to the prognosis of GAC patients. A risk score formula of 6 prognosis-related ERGs used to predict the prognosis of gastric adenocarcinoma patients is identified and tested (risk score=0.448115∗expression value of MMP8+0.378892∗expression value of MMP11−0.3226∗expression value of MYB+1.322812∗expression value of TFDP3+0.325063∗expression value of F2+0.334197∗expression value of CNTN1). Conclusion. This study provides a potential prognostic signature for predicting prognosis of gastric adenocarcinoma patients and molecular insights of EMT in gastric adenocarcinoma, and the formula focusing on the prognosis of gastric adenocarcinoma can be effective.

Background Endoscopic retrograde appendicitis therapy (ERAT) is a new and minimally invasive technique for the treatment of acute appendicitis. This study aimed to assess the efficacy and clinical outcomes of ERAT versus laparoscopic appendectomy for patients with uncomplicated acute appendicitis. Methods We adopted propensity score matching (1:1) to compare ERAT and laparoscopic appendectomy in patients with uncomplicated acute appendicitis between April 2017 and March 2020. We reviewed 2880 patients with suspected acute appendicitis, of whom 422 patients with uncomplicated acute appendicitis met the matching criteria (ERAT 79; laparoscopic appendectomy 343), yielding 78 pairs of patients. Results The rate of curative treatment within 1 year after ERAT was 92.1 % (95 % confidence interval [CI] 83.8 % to 96.3 %). The percentage of patients recording visual analog scale values of ≤ 3 for pain at 6 hours after treatment was 94.7 % (95 %CI 87.2 % to 97.9 %) in the ERAT group, which was significantly higher than that in the laparoscopic appendectomy group (83.3 %; 95 %CI 73.5 % to 90.0 %). Median procedure time and median hospital length of stay were significantly lower in the ERAT group compared with the laparoscopic appendectomy group. At 1 year, the median recurrence time was 50 days (interquartile range 25–127) in the ERAT group. The overall adverse event rate was 24.4 % (95 %CI 14.8 % to 33.9 %) in the laparoscopic appendectomy group and 18.4 % (95 %CI 9.7 % to 27.1 %) in the ERAT group, with no significant difference between the two groups. Conclusion ERAT was a technically feasible method of treating uncomplicated acute appendicitis compared with laparoscopic appendectomy.

Background The ecology and evolution of phoretic mites and termites have not been well studied. In particular, it is unknown whether the specific relationship between mites and termites is commensal or parasitic. High phoretic mite densities have often been found to occur in weak termite colonies, suggesting that the relationship is closer to that of parasitism than commensalism. Results To examine this, Coptotermes formosanus was used as a carrier, and Acarus farris as the phoretic mite. We used video recordings to observe termite social immunity behaviors and bioassay to examine termite fitness. Our results showed that the attachment of the mite on the termite can enhance termite social immunity behaviors like alarm vibration and grooming frequency while decreasing the duration of individual grooming episodes in phoretic mites. Further, A. farris phoresy led to a 22.91% reduction in termite abdomen volume and a 3.31-fold increase in termite mortality. Conclusions When termites groom more frequently, the consequence is short duration of grooming bouts. This may be indicative of a trade-off which provides suggestive evidence that frequent social behaviors may cost termites energy. And this caused phoretic behavior hastened termites’ death, and helped propagate the population of mites feeding on dead termites. So, it provides a case for phoresy being a precursor to parasitism, and the specific relationship between A. farris and C. formosanus is closer to parasitism than to commensalism.

Background: Granular cell tumors (GCTs) are rare tumors probably originating from neurogenic Schwann cells. The aim was to evaluate the safety and feasibility of endoscopic resection for esophageal GCTs. Methods: The study retrospectively analyzed patients with pathologically diagnosed esophageal GCTs in our center from February 2012 to December 2020. Clinicopathological characteristics, endoscopic features and clinical outcomes were collected and analyzed. Results: 12 males and 10 females were identified. Lesions were located in the upper, middle and lower esophagus in three, six and thirteen cases respectively. 14 lesions (63.6%) exhibited white-to-yellow discoloration. The mean maximum diameter of these lesions was 5.7±2.2 mm (range 2-11.6 mm). The most lesions (91%) were located in the mucosa or submucosa layer, and 2 lesions (9.0%) were in the muscularis propria layer. Endoscopic mucosal resection (n=17), endoscopic submucosal dissection (n=4) and endoscopic submucosal excavation (n=1) were performed. En bloc resection was achieved in 20 lesions (90.9%). The R0 resection was achieved in 20 lesions (90.9%). No patients experienced intraoperative perforation or delayed bleeding in the mean length of postoperative hospital stay of 4.2±2.1 days (range 1-9 days). All patients had no recurrence or metastasis during the mean follow-up period of 48.1±27.2 months (range 2-102 months). Conclusion: Endoscopic resection is safe and effective for management of esophageal GCTs. Clinically, the appropriate approach of endoscopic resection should be selected according to the origin and size of the lesion.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, which often affects colon or rectum or both. It is now well recognized that sphingosine kinases-1/sphingosine-1-phosphate (S1P) signaling may have a very significant potential as targets for therapeutic intervention in UC. Compared with the pure dextran sodium sulfate group, administration of PF543 significantly reduced clinical symptoms with less weight loss, diarrhea, and shortening of the colon. The severity of colitis was improved with reduced disease activity index and degree of histological damage in colon. Moreover, treatment with PF543 not only decreased S1P but also inhibited mRNA expression of proinflammatory factors such as interleukin (IL)-1β and IL-6. This suggests that PF543 might exhibit an anti-inflammatory function against colitis through inhibition of expression of proinflammatory factors.

BACKGROUND Ulcerative colitis is a chronic, idiopathic inflammatory disease that destroys the colon structure. Nevertheless, the exact pathogenesis is not clear and needs to be fully elucidated. MATERIAL AND METHODS Stool and plasma samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry, respectively. In addition, we detected the level of trimethylamine N-oxide. Finally, we performed Pearson correlation analysis between the microbiome and the metabolome. RESULTS Twenty-three active ulcerative colitis, 25 inactive ulcerative colitis, and 30 control cases were included. Thirty-four significantly different metabolites were found between the active ulcerative colitis and control groups, 38 were found between the inactive ulcerative colitis and control groups, and only 1 was found between the active ulcerative colitis and inactive ulcerative colitis groups. The plasma trimethylamine N-oxide level of the inactive ulcerative colitis and active ulcerative colitis groups was significantly higher than that of the control group. Moreover, we identified significant changes in 24, 18, and 12 bacterial genera for active ulcerative colitis-control, inactive ulcerative colitis-control, and active ulcerative colitis-inactive ulcerative colitis, respectively. Cross-correlation indicated an association between sphingosine 1-phosphate and Roseburia, Klebsiella, and Escherichia-Shigella. Through the pathway analysis, we found sphingolipid metabolism was one of the most significantly increased pathways. CONCLUSIONS Although levels of trimethylamine N-oxide were higher in ulcerative colitis patients, they did not achieve statistical significance in active ulcerative colitis and inactive ulcerative colitis groups. Sphingosine 1-phosphate was increased in ulcerative colitis patients and there were several microbiota associated with it. Although further study is still needed, sphingosine 1-phosphate will probably become a new target for treatment of ulcerative colitis.

Background and objective Endoscopic submucosal dissection (ESD) is a minimal invasive technology and could allow “en bloc” resection for superficial gastric tumors. The aim of this study is to evaluate the safety and feasibility of ESD for gastric ectopic pancreas (EP). Methods A total of 93 patients diagnosed with ectopic pancreas who underwent ESD between January 2011 and June 2017 were enrolled. The demographic, clinical, and endoscopic data were collected and analyzed. Results The average maximal diameter of lesions was 1.01 (range 0.4–3.0) cm with mean age of patients which was 39.75 (range 15–66) years. Overall, all of procedures en bloc was successful. The median operative time was 76.87 (range 30–160) min. A total of 12 patients experienced complications. In seven patients, bleeding occurred during the operation and was treated using hot biopsy forceps or metal clip. Five cases suffered from pneumoperitoneum which was managed well. The mean length of postoperative hospital stay was 5.7 (range 2–17) days. There was no relapse in any cases during the follow-up. Conclusion ESD appears to be a safe and feasible approach for curative treatment in gastric ectopic pancreas. Larger studies are needed to identify the role and the outcomes of ESD in another center.

Aiming at the low efficiency and low quality detection level of the manual infusion set, a gas detection system for infusion set based on STM32 single-chip microcomputer was designed. The detection system includes hardware system design and software system design. The hardware system is based on the STM32F103 single-chip microcomputer. It mainly designs the gas pressure sensor acquisition circuit and the multi-way solenoid valve control circuit. The software system uses a C ++ real-time operating system to ensure system monitoring's real-time performance and validity. Test data is transmitted to the upper computer and displayed via USB serial communication. The experiment proves that the infusion set gas detection system can perform gas detection on the infusion set. The system has the characteristics of stability and high accuracy. The relative error of the experimental measurement is within ±5%, and the detection efficiency is better than manual detection.

BACKGROUND Colorectal cancer (CRC) is the third most common cancer worldwide, making it is a serious threat to human health. It is imperative to develop new therapeutics to improve the CRC treatment efficiency. The aim of this study was to investigate the role of NPRL2 in improving sensitivity to CPT-11 in colon cancer cells. MATERIAL AND METHODS NPRL2 overexpression was established by transfecting the recombinant lentivirus-encoding NPRL2 gene into HCT116 colon cancer cells. Cell proliferation was identified using Cell Counting Kit-8 (CCK8) assay. Cell cycle and apoptosis were examined by flow cytometry. An immunofluorescence staining assay was conducted to examine the expression of γ-H2AX. Wound-healing and Transwell assays were utilized to show cell migration and invasion capability. The expression of apoptosis-related proteins (cleaved caspase-3, caspase-9, cleaved PARP, BAX, and Bcl-2), invasion-related proteins (MMP2, MMP9, p-PI3K, and p-AKT), and DNA damage checkpoint pathway proteins (p-ATM, p-Chk2, Cdc25C, Cdc2, and Cyclin B1) were quantified by Western blotting. RESULTS A CCK8 assay revealed that the overexpression of NPRL2 improved the sensitivity of CPT-11 in HCT116 cells (P

Objective This report describes a mini-invasive technique called endoscopic full-thickness resection (EFR) for the treatment of gastric subepithelial tumors (SETs) originating from the muscularis propria (MP). Materials and methods We retrospectively analyzed 69 patients with gastric SETs originating from the MP at our hospital between September 2009 and July 2016. The data from each patient were reviewed, including patient information, tumor characteristics, procedure-related data, and recurrence rates. Results Successful complete resection by EFR was achieved in 69 cases. The complete resection rate was 100%, and the mean resected tumor size was 2.25±1.40 (range, 0.6 to 6) cm. No residual tumor recurrence was detected during the follow-up period in 57 patients. The other 12 patients were lost to follow-up. Conclusions EFR seems to be a safe and effective technique for the treatment of patients with gastric SETs originating from the MP.

Colorectal cancer (CRC) is one of the most leading causes of cancer deaths worldwide. In the study, we aimed to identify key long non-coding RNAs (lncRNAs) significantly associated with prognosis of CRC and develop an expression-based lncRNA signature to provide survival risk prediction for CRC patients. LncRNA expression profiles and clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Six hundred and eighteen differentially expressed lncRNAs were identified between CRC and normal tissues. After univariate and multivariate Cox regression analysis for these differentially expressed lncRNAs and overall survival of CRC patients, six predictive lncRNAs (RP1-170O19.17, RP11-785D18.3, RP11-798K3.2, XXbac-B476C20.9, RP11-481J13.1, and RP11-167H9.4) were finally screened out to construct a six-lncRNA signature, based on which patients in the training dataset were divided into the high-risk and low-risk group with significantly different overall survival. ROC curve analysis demonstrated competitive performance of the six-lncRNA signature. The prognostic power of the six-lncRNA signature was successfully validated in the testing and entire dataset. Multivariate Cox regression analysis and stratification analysis further suggested that the six-lncRNA signature was independent of other conventional clinical variables for survival prediction in CRC patients. Functional enrichment analysis revealed the possible roles of these predictive lncRNAs in some cancer-related biological processes and pathways. Our study demonstrated the promising potential of the novel six-lncRNA signature as an independent biomarker for survival prediction of CRC patients.

Background & aims Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma (HCC) cells. However, how they influence the migration of tumour cells remained largely unknown. Methods In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of hepatocellular carcinoma cells. Moreover, the underlying molecular mechanisms and therapeutic application were explored. Results Our data showed that dynamin-1-like protein expression was strongly increased in distant metastasis of hepatocellular carcinoma when compared to primary hepatocellular carcinoma. In contrast, the mitochondrial fusion protein mitofusin 1 showed an opposite trend. Moreover, the expression of dynamin-1-like protein and mitofusin 1 was significantly associated with the disease-free survival of hepatocellular carcinoma patients. In addition, our data further showed that mitochondrial fission significantly promoted the reprogramming of focal-adhesion dynamics and lamellipodia formation in hepatocellular carcinoma cells mainly by activating typical Ca2+ /CaMKII/ERK/FAK pathway. Importantly, treatment with mitochondrial division inhibitor-1 significantly decreased calcium signalling in hepatocellular carcinoma cells and had a potential treatment effect for hepatocellular carcinoma metastasis in vivo. Conclusions Taken together, our findings demonstrate that mitochondrial fission plays a critical role in the regulation of hepatocellular carcinoma cell migration, which provides strong evidence for this process as a drug target in hepatocellular carcinoma metastasis treatment.

BACKGROUND Hepatocellular carcinoma (HCC) is a malignant tumor which is famous for its high heterogeneity and complex pathogenesis. Angiogenesis is an important driver of tumor progression and immune-suppressive microenvironment formation. MATERIAL AND METHODS A training set was acquired from the TCGA-LIHC cohort. An angiogenesis-active subtype was identified by consensus clustering analysis. The tumor subtype's immune microenvironment pattern was analyzed using quanTIseq. DEGs-mediated biology function was analyzed by enrichment analysis based on GO and KEGG. A prognostic model was constructed using LASSO Cox regression analysis and validated by 2 external datasets derived from GEO and ICGC. Quantitative real-time PCR assay was conducted to analyze CDCA8's expression status in the HCC line and normal liver cell line. RESULTS In HCC, patients with the angiogenesis-active subtype had a poor prognosis. Angiogenesis can shape the tumor microenvironment into high-M2 microphage infiltration and activity pattern. Here, we identified an angiogenesis-active HCC subtype and constructed an angiogenesis feature-based prognostic model to predict patient outcome. The external validation sets were enrolled to verify the accuracy of this model. CONCLUSIONS Our research demonstrated angiogenesis can confer the tumor immune-suppressive characteristic. We provide a robust method to evaluate the HCC's angiogenesis potential and help identify the angiogenesis-active subtype. Validation in the external validation cohort further confirmed the accuracy of our prognostic model.

Both mitochondrial morphology and the level of cytosolic calcium [Ca2+]c are actively changed and play critical roles in a number of malignancies. However, whether communications existed between these two processes to ingeniously control the malignant phenotype are far from clear. We investigated the reciprocal regulation between mitochondrial fission and cytosolic calcium signaling in human hepatocellular carcinoma (HCC) cells. Furthermore, the underlying molecular mechanisms and the synergistic effect on autophagy were explored. Our results showed that mitochondrial fission increased the [Ca2+]c and calcium oscillation in HCC cells. We further found that mitochondrial fission-mediated calcium signaling was dependent on ROS-activated NF-κB pathways, which facilitated the expression of STIM1 and subsequent store-operated calciumentry. Additionally, we also demonstrated that increase in [Ca2+]c promoted mitochondrial fission by up-regulating expression of Drp1 and FIS1 via transcription factors NFATC2 and c-Myc, respectively. Moreover, the positive feedback loop significantly promoted HCC cell global autophagy by Ca2+/CAMKK/AMPK pathway. Our data demonstrate a positive feedback loop between mitochondrial fission and cytosolic calcium signaling and their promoting role in autophagy of HCC cells, which provides evidence for this loop as a potential drug target in tumor treatment.

BACKGROUND Accumulating evidence suggests the involvement of long non-coding RNAs (lncRNAs) as oncogenic or tumor suppressive regulators in the development of various cancers. In the present study, we aimed to identify a lncRNA signature based on RNA sequencing (RNA-seq) data to predict survival in esophageal cancer. MATERIAL AND METHODS The RNA-seq lncRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs were screened out between esophageal cancer and normal tissues. Univariate and multivariate Cox regression analysis were performed to establish a lncRNA-related prognostic model. Receiver operating characteristic (ROC) analysis was conducted to test the sensitivity and specificity of the model. GO (gene ontology) functional and KEGG pathway enrichment analyses were performed for mRNAs co-expressed with the lncRNAs to explore the potential functions of the prognostic lncRNAs. RESULTS A total of 265 differentially expressed lncRNAs were identified between esophageal cancer and normal tissues. After univariate and multivariate Cox regression analysis, eight lncRNAs (GS1-600G8.5, LINC00365, CTD-2357A8.3, RP11-705O24.1, LINC01554, RP1-90J4.1, RP11-327J17.1, and LINC00176) were finally screened out to establish a predictive model by which patients could be classified into high-risk and low-risk groups with significantly different overall survival. Further analysis indicated independent prognostic capability of the 8-lncRNA signature from other clinicopathological factors. ROC curve analysis demonstrated good performance of the 8-lncRNA signature. Functional enrichment analysis showed that the prognostic lncRNAs were mainly associated with esophageal cancer related biological processes such as regulation of glucose metabolic process and amino acid and lipids metabolism. CONCLUSIONS Our study developed a novel candidate model providing additional and more powerful prognostic information beyond conventional clinicopathological factors for survival prediction of esophageal cancer patients. Moreover, it also brings us new insights into the molecular mechanisms underlying esophageal cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Editor-in-Chief and the authors. The journal was initially contacted by the corresponding author to request the retraction of the article because the author claimed that part of the paper was outsourced to a third-party company who offered them the “wrong picture”. During the investigation, the Editor became aware of allegations about this article on Pubpeer. Figure 7E is similar to Figure 7F from the article published by Xiaoping Pan, Chen Wang, Yan Li, Lida Zhu and Ti Zhang in Life Sciences, 214, (2018) 124-135 https://doi.org/10.1016/j.lfs.2018.10.064, a similar portion of Figure 6D from the article published by Qiang Wang, Yi Yan, Jie Zhang, Peng Guo, Yuqing Xing, Yong Wang, Fawei Qin and Qingyun Zeng in BiomedicinePharmacotherapy, 104, (2018) 28-35 https://doi.org/10.1016/j.biopha.2018.05.013, portions of Figure 6C from the article published by Jun Zou, Yamei Wang, Mingdi Liu, Xiushu Huang, Wenjian Zheng, Qian Gao, Haijing Wang in Cell Biochemistry and Function, 36, (2018) 303-311 https://doi.org/10.1002/cbf.3349, portions of Figure 8C from the article published by Kaili Liu, Hui Gao, Qiaoyun Wang , Longyuan Wang, Bin Zhang , Zhiwu Han, Xuehong Chen, Mei Han, and Mingquan Gao in Cancer Science, 109, (2018) 1369-1381 https://doi.org/10.1111/cas.13575, portions of Figure 8D of the article published by Xiangyang Dou, Meihua Wang, Tao Zhang and Jiapei Yao in The Anatomical Record, 303, (2020) 3117-3128 https://doi.org/10.1002/ar.24324, portions of Figure 6F from the article published by Xuezhu Lin, Mingquan Gao, Ailing Zhang, Jingjie Tong, Xiaoyi Zhang, Quanzhong Su, Zhihong Yang, Hui Gao and Guohui Jiang in Life Sciences 239, (2019) 117074 https://doi.org/10.1016/j.lfs.2019.117074, portions of 6F from the article published by Luping Wang, Lu Yun, Xiaojun Wang, Liying Sha, Luning Wang, Yingying Sui and Hui Zhang in Life Sciences, 218, (2019) 16-24 https://doi.org/10.1016/j.lfs.2018.12.023, and portions of Figure 7F from the article published by Dong Li, Xiaoyan Li , Genqu Li , Yan Meng , Yanghong Jin , Shuang Shang , Yanjie Li in Life Sciences, 216, (2019) 259-270 https://doi.org/10.1016/j.lfs.2018.11.032. The journal requested the authors to provide the raw data. However, the authors were not able to fulfill this request and therefore the Editor-in-Chief has decided to retract the article.

Background/aims Colon cancer remains a life-threating disease with increasing morbidity and mortality worldwide despite the advancement in modern medical treatment. Therefore, novel and effective anti-colon cancers drugs are urgently needed. In this study, we investigated the anti-metastatic property EnDuo, a modified version of Endostar, and the underlying mechanisms. Methods Colon cancer cells were treated with different concentrations of EnDuo (50 μg/mL, 100 μg/mL, 200 μg/mL), and Endostar (100 μg/mL) as positive control. Cell Counting Kit-8 assay was performed to test the effect of EnDuo on cell viability. A scratch wound assay and transwell assay were employed to evaluate the relocation and motility of malignant colon cells following treatment with EnDuo. Western blot analysis was used to determine inhibitory effects of EnDuo by detecting the phosphorylation level of AKT and ERK proteins, and the expression of MMP-2 and MMP-9 proteins. Results Our results showed that EnDuo impedes the migration of colon cancer cells in a dose-dependent manner. At the molecular level, EnDuo induced a significant reduction in the phosphorylation of AKT and ERK proteins, and inhibited the expression of MMP-2 and MMP-9 proteins. Conclusions Collectively, these results demonstrate that EnDuo exhibits a comparable anti-metastatic effect by suppressing the migration of colon cancer cells. Possibly, EnDuo interrupts the PI3K/AKT/ERK signaling pathway to arrest cell migration. Our study provides a novel insight to the potential clinical applications of EnDuo against colon cancers in the future.

// Lei Zhan 1 , Haiyan Cao 2 , Gang Wang 2 , Yinghua Lyu 2 , Xiacheng Sun 2 , Jiaze An 3 , Zhenbiao Wu 4 , Qichao Huang 2 , Bingrong Liu 1 , Jinliang Xing 2 1 Department of Gastroenterology, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China 2 State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi’an, 710032, China 3 Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China 4 Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China Correspondence to: Bingrong Liu, email: bingrongliu@qq.com Jinliang Xing, email: xingjl@fmmu.edu.cn Keywords: mitochondrial dynamics, cell proliferation, liver cancer, p53, NF-κB Received: April 18, 2016 Accepted: July 28, 2016 Published: August 17, 2016 ABSTRACT Mitochondria are highly dynamic and undergo constant fusion and fission that are essential for maintaining physiological functions of cells. Recently, we have reported that increased mitochondrial fission promotes autophagy and apoptosis resistance in hepatocellular carcinoma (HCC) cell through ROS-mediated coordinated regulation of NF-κB and p53 pathways. However, little is known about the roles of mitochondrial dynamics in HCC cell proliferation, another key feature of cancer cells. In this study, we systematically investigated the functional role of mitochondrial fission in the regulation of HCC cell proliferation. Furthermore, the underlying molecular mechanisms were deeply explored. We found that, increased mitochondrial fission by forced expression of Drp1 promoted the proliferation of HCC cells both in vitro and in vivo mainly by facilitating G1/S phase transition of cell cycle. Whereas, Drp1 knockdown or treatment with mitochondrial division inhibitor-1 induced significant G1 phase arrest in HCC cells and reduced tumor growth in the xenotransplantation model. We further demonstrated that the proliferation-promoting role of Drp1-mediated mitochondrial fission was mediated via p53/p21 and NF-κB/cyclins pathways. Moreover, the crosstalk between p53 and NF-κB pathways was proved to be involved in the regulation of mitochondrial fission-mediated cell proliferation. In conclusion, our findings demonstrate that Drp1-mediated mitochondrial fission plays a critical role in the regulation of cell cycle progression and HCC cell proliferation. Thus, targeting Drp1-dependent mitochondrial fission may provide a novel strategy for suppressing tumor growth of HCC.

miR-145-5p has been reported to be downregulated and described functioning as a tumor suppressive gene in colorectal cancer (CRC), yet its detailed regulatory function and mechanism in malignant progression of the disease have not been thoroughly understood. In our study, miR-145-5p and rhomboid domain containing 1 (RHBDD1) in CRC tissues and cells were examined by qRT-PCR and western blot. MTT, colony formation, wound healing, Transwell invasion, and flow cytometry assays were performed to evaluate the malignant phenotypes of CRC cells. Xenograft tumor, qRT-PCR, and western blot assays were applied to validate the roles and mechanism of miR-145-5p in CRC in vivo. The interaction between miR-145-5p and RHBDD1 was investigated by luciferase reporter assay and western blot. The changes of the EGFR/Raf/MEK/ERK pathway were detected by western blot. We found miR-145-5p was lowly expressed and low miR-145-5p predicted poor prognosis in CRC, while RHBDD1 was greatly enhanced in CRC cells and tissues. RHBDD1 silencing resulted in inhibiting cell proliferative, invasive, and migratory potentials as well as elevating apoptotic ones in CRC cells. miR-145-5p was inversely related with RHBDD1 expression in CRC tissues. miR-145-5p was found to directly bind to RHBDD1 and restrained its expression in CRC cells. miR-145-5p overexpression repressed CRC cell proliferation, invasion, migration and induced apoptosis, and these effects were reversed by RHBDD1 upregulation. Moreover, in CRC xenograft tumor, its growth was impeded by miR-145-5p via suppressing RHBDD1. Furthermore, miR-145-5p inhibited the expression of EGFR, p-MEK1/2 and p-ERK1/2, in vitro and in vivo by targeting RHBDD1. In conclusion, our study revealed that miR-145-5p overexpression inhibited tumorigenesis in CRC by downregulating RHBDD1 via suppressing the EGFR-associated signaling pathway (EGFR/Raf/MEK/ERK cascades).

Qiaowei Fan,1,2 Bingrong Liu1 1Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang, People’s Republic of China Purpose: This study was aimed to develop a lncRNA-associated competing endogenous RNA (ceRNA) network to provide further understanding of the ceRNA regulatory mechanism and pathogenesis in colorectal cancer (CRC).Patients and methods: Expression profiles of mRNAs, lncRNAs, and miRNAs, and clinical information for CRC patients were obtained from The Cancer Genome Atlas. The differentially expressed mRNAs, lncRNAs, and miRNAs (referred to as “DEmRNAs”, “DElncRNAs”, and “DEmiRNAs”, respectively) were screened out between 539 CRC samples and 11 normal samples. The interactions between DElncRNAs and DEmiRNAs were predicted by miRcode. The DEmRNAs targeted by the DEmiRNAs were retrieved according to TargetScan, miRTarBase, and miRDB. The lncRNA–miRNA–mRNA ceRNA network was constructed based on the DEmiRNA–DElncRNA and DEmiRNA–DEmRNA interactions. Functional enrichment analysis revealed the biological processes and pathways of DEmRNAs involved in the development of CRC. Key lncRNAs were further analyzed for their associations with overall survival and clinical features of CRC patients.Results: A total of 1,767 DEmRNAs, 608 DElncRNAs, and 283 DEmiRNAs were identified as CRC-specific RNAs. Three hundred eighty-two DEmiRNA–DElncRNA interactions and 68 DEmiRNA–DEmRNA interactions were recognized according to the relevant databases. The lncRNA–miRNA–mRNA ceRNA network was constructed using 25 DEmiRNAs, 52 DEmRNAs, and 64 DElncRNAs. Two DElncRNAs, five DEmiRNAs, and six DEmRNAs were demonstrated to be related to the prognosis of CRC patients. Four DElncRNAs were found to be associated with clinical features. Twenty-eight Gene Ontology terms and 10 Kyoto Encyclopedia of Genes and Genomes pathways were found to be significantly enriched by the DEmRNAs in the ceRNA network.Conclusion: Our results showed cancer-specific mRNA, lncRNA, and miRNA expression patterns and enabled us to construct an lncRNA-associated ceRNA network that provided new insights into the molecular mechanisms of CRC. Key RNA transcripts related to the overall survival and clinical features were also found with promising potential as biomarkers for diagnosis, survival prediction, and classification of CRC. Keywords: colorectal cancer, competing endogenous RNA network, long noncoding RNA, survival analysis