PDPN/CCL2/STAT3 feedback loop alter CAF heterogeneity to promote angiogenesis in colorectal cancer.

Colorectal cancer (CRC) is one of the common clinical malignancies and the fourth leading cause of cancer-related death in the world. The tumor microenvironment (TME) plays a crucial role in promoting tumor angiogenesis, and cancer-associated fibroblasts (CAFs) are one of the key components of the tumor microenvironment. However, due to the high heterogeneity of CAFs, elucidating the molecular mechanism of CAF-mediated tumor angiogenesis remained elusive. In our study, we found that there is pro-angiogenic functional heterogeneity of CAFs in colorectal cancer and we clarified that Podoplanin (PDPN) can specifically label CAF subpopulations with pro-angiogenic functions. We also revealed that PDPN + CAF could maintain CAF heterogeneity by forming a PDPN/CCL2/STAT3 feedback loop through autocrine CCL2, while activate STAT3 signaling pathway in endothelial cells to promote angiogenesis through paracrine CCL2. We demonstrated WP1066 could inhibit colorectal cancer angiogenesis by blocking both the PDPN/CCL2/STAT3 feedback loop in CAFs and the STAT3 signaling pathway in endothelial cells. Altogether, our study suggests that STAT3 could be a potential therapeutic target for blocking angiogenesis in colorectal cancer. We provide theoretical basis and new therapeutic strategies for the clinical treatment of colorectal cancer.

Identification of Hub Genes for Psoriasis and Cancer by Bioinformatic Analysis.

Psoriasis increases the risk of developing various cancers, including colon cancer. The pathogenesis of the co-occurrence of psoriasis and cancer is not yet clear. This study is aimed at analyzing the pathogenesis of psoriasis combined with cancer by bioinformatic analysis. Skin tissue data from psoriasis (GSE117239) and intestinal tissue data from colon cancer (GSE44076) were downloaded from the GEO database. One thousand two hundred ninety-six common differentially expressed genes and 688 common shared genes for psoriasis and colon cancer were determined, respectively, using the limma R package and weighted gene coexpression network analysis (WGCNA) methods. The results of the GO and KEGG enrichment analyses were mainly related to the biological processes of the cell cycle. Thirteen hub genes were selected, including AURKA, DLGAP5, NCAPG, CCNB1, NDC80, BUB1B, TTK, CCNB2, AURKB, TOP2A, ASPM, BUB1, and KIF20A. These hub genes have high diagnostic value, and most of them are positively correlated with activated CD4 T cells. Three hub transcription factors (TFs) were also predicted: E2F1, E2F3, and BRCA1. These hub genes and hub TFs are highly expressed in various cancers. Furthermore, 251 drugs were predicted, and some of them overlap with existing therapeutic drugs for psoriasis or colon cancer. This study revealed some genetic mechanisms of psoriasis and cancer by bioinformatic analysis. These hub genes, hub TFs, and predicted drugs may provide new perspectives for further research on the mechanism and treatment.

Fading suppression in the Ф-OTDR system based on a phase-modulated optical frequency comb.

In this paper, what we believe to be a novel method is proposed to suppress the fading effect of the phase-sensitive optical time domain reflectometer (Ф-OTDR) by using a phase-modulated optical frequency comb. In the Ф-OTDR system, intensity distributions of Rayleigh backscattering (RBS) light are different for pulsed probe lights with different central frequencies, therefore the locations of the fading points corresponding to signals of different frequencies are differently distributed, allowing the use of frequency division multiplexing to suppress the fading effects. In the experimental system of this paper, a continuous light in the form of a frequency comb is firstly generated through phase modulation. It is then modulated into a pulsed probe light and injected into the sensing fiber to produce different RBS intensity distributions. Finally, the extracted phase is processed by using the amplitude evaluation method, so that the distorted phase can be eliminated. Fading suppression is achieved using our system, and the effect of suppression is evaluated. By using an equal-amplitude optical frequency comb containing seven frequency components, the fading probability density of the system is dramatically reduced from the range of 5.49%-9.83% to 0.08%. Compared with the conventional system using a single acoustic-optic modulator to generate the frequency shift, the method proposed in this paper features a larger modulation bandwidth and more flexible frequency combination scheme to better suppress the fading effect. This method does not sacrifice the response bandwidth of the system, and the phase delay can be precisely controlled, which helps to fully suppress the fading effect.

Impact of endoscopic metallic stent placement and emergency surgery on detection of viable circulating tumor cells for acute malignant left-sided colonic obstruction.

BACKGROUND: Self-expanding metal stents (SEMS) served as a bridge to surgery (BTS). However, this method may be associated with worse long-term prognosis and relapse of CRC patients. Therefore, we attempted to clarify this in the angle of circulating tumor cells (CTCs). METHODS: A multicenter study was performed from March 2018 to January 2021. Thirty-two colorectal cancer patients with obstruction were selected, of which 21 patients were performed SEMS as a BTS while 11 patients were performed emergency surgery. Bloods samples were collected in two groups of patients for further detecting CTCs. In the SEMS group, the samples were collected before and after stent insert and after radical surgery performed. In the ES group, the samples were collected before stent insert and after emergency surgery performed. RESULTS: The number of CTCs did not show statistically significant differences before and after stent placement (34.90 vs 38.33, p=0.90), neither between the SEMS group and ES group in initial CTC levels (34.90 vs 58.09, p=0.394). No significant differences (38.33 vs 58.09, p=0.632) were observed after stent insert in the SMES group and the initial CTC levels in the ES group. Moreover, no major differences (24.17 vs 42.27, p=0.225) were observed after radical operation performed in both groups. CONCLUSION: The treatment of SEMS does not cause an increase in the number of CTC after stent insertion. Furthermore, there are may be other factors besides CTC to cause these poorer oncologic outcomes after SEMS placement.

Distributed Airflow Sensing Based on High-Spatial-Resolution BOTDA and a Self-Heated High-Attenuation Fiber.

An all-fiber distributed airflow sensing method based on a differential pulse-width pair Brillouin optical time domain analysis (DPP-BOTDA) and a self-heated high-attenuation fiber (HAF) is proposed and demonstrated. The HAF heated the sensing fiber, producing a gradient temperature distribution in it through physical contact, where the temperature distribution was obtained by DPP-BOTDA with a spatial resolution of 5 cm. The heat loss caused by the airflow was reflected in the decrease in the Brillouin frequency shift and spatially resolved by DPP-BOTDA. Distributed airflow sensing was experimentally demonstrated for measurements of airflow movement, multiple airflow sources and the deflection angle of the airflow. The positioning error of the airflow was no larger than ~2.2 cm; for the deflection angle measurements of the airflow, the maximum demodulation error was 2.5° within the angle range of 0-30°.

Hollow CeO2 with ROS-Scavenging Activity to Alleviate Colitis in Mice.

INTRODUCTION: Excessive production of reactive oxygen species (ROS) to induce high oxidative stress is one of the main causes of colitis; thus, it has been regarded as a therapeutic target for colitis treatment. And the nanomaterial-based therapeutic strategies are effective against colitis. However, the previous elaborately designed materials exhibit limited application due to the uncertain biocompatibility and complicated manufacturing processes. METHODS: In this study, the highly monodisperse hollow CeO2 nanoparticles (H-CeO2) with uniform morphology were obtained by in situ growing CeO2 on solid silica nanoparticles and subsequently removing the silica core. The H-CeO2 was further modified with PEG, which owned excellent biological stability and biocompatibility. The experimental model of colitis induced by dextran sulfate sodium (DSS) was used to investigate the anti-inflammatory effect of H-CeO2-PEG. RESULTS: The H-CeO2-PEG showed good ROS scavenging efficacy and decreased the levels of proinflammatory cytokines (IL-6, IL-1ß, IL-18, and TNF-α) in DSS-induced colitis mice. Furthermore, H-CeO2-PEG inhibited the activation of the MAPK signalling pathway to alleviate colitis. CONCLUSION: This study reveals the therapeutic effects of CeO2-based nanomedicine toward colitis and elucidates the specific signalling pathway involved, which provides potential alternative therapeutic options for patients with inflammation tissue.

PLXNC1: A Novel Potential Immune-Related Target for Stomach Adenocarcinoma.

BACKGROUND: Gastric cancer is associated with tumor microenvironment and chronic inflammation, but the underlying tumor-promoting mechanisms still remain unknown. METHODS: The ATAC-seq was used to identify genes with chromatin accessibilities in promoter regions. The RNA-seq datasets were performed to identify differentially expressed genes (DEGs). Pearson correlation analysis with the mRNA expression of three families of tumor-related inflammation TFs was used to filter downstream DEGs. Cox univariate survival analysis was performed to identify the prognostic value. The ImmPort database and CIBERSORTx algorithm were used to investigate the regulatory relationship between hub DEGs and immune cells. Immunohistochemistry (IHC) and multidimensional database were performed to verification. RESULTS: In this case, we require 2,454 genes with chromatin accessibility in promoter regions by ATAC-seq. Based on the gene expression profiles (RNA-seq), we identified 365 genes with chromatin accessibility and differential expression. Combined with the Cox univariate survival analysis, we identified 32 survival-related DEGs with chromatin accessibility. According to ImmPort database, CXCL3, PLXNC1, and EDN2 were identified as immune- related genes in STAD. By applying the CIBERSORTx algorithm and Pearson correlation, PLXNC1 was the only gene correlated with various immune cells, significantly associated with M2 macrophages. Furthermore, gene set variation analysis (GSVA) suggests the "hallmark_interferon_gamma_response" pathway was most significantly correlated with PLXNC1. Immunohistochemistry results revealed that PLXNC1 protein level was significantly higher in STAD tissues than in normal tissues (p < 0.001). CONCLUSION: PLXNC1, regulated by IRF5, is an immune-related gene that was significantly associated with M2 macrophages and poor outcome in stomach adenocarcinoma.

Erratum: Chemopreventive effect of 4'-hydroxychalcone on intestinal tumorigenesis in ApcMin mice.

[This corrects the article DOI: 10.3892/ol.2021.12474.].

Propensity score-matched comparison of stenting as a bridge to surgery and emergency surgery for acute malignant left-sided colonic obstruction.

BACKGROUND: Bridge to elective surgery (BTS) using self-expanding metal stents (SEMSs) is a common alternative to emergency surgery (ES) for acute malignant left-sided colonic obstruction (AMLCO). However, studies regarding the long-term impact of BTS are limited and have reported unclear results. METHODS: A multicenter observational study was performed at three hospitals from April 2012 to December 2019. Propensity score matching (PSM) was introduced to minimize selection bias. The primary endpoint was overall survival. The secondary endpoints included surgical approaches, primary resection types, total stent-related adverse effects (AEs), surgical AEs, length of hospital stay, 30-day mortality and tumor recurrence. RESULTS: Forty-nine patients in both the BTS and ES groups were matched. Patients in the BTS group more often underwent laparoscopic resection [31 (63.3%) vs. 8 (16.3%), p < 0.001], were less likely to have a primary stoma [13 (26.5%) vs. 26 (53.1%), p = 0.007] and more often had perineural invasion [25 (51.0 %) vs. 13 (26.5 %), p = 0.013]. The median overall survival was significantly lower in patients with stent insertion (41 vs. 65 months, p = 0.041). The 3-year overall survival (53.0 vs. 77.2%, p = 0.039) and 5-year overall survival (30.6 vs. 55.0%, p = 0.025) were significantly less favorable in the BTS group. In multivariate Cox regression analysis, stenting (hazard ratio(HR) = 2.309(1.052-5.066), p = 0.037), surgical AEs (HR = 1.394 (1.053-1.845), p = 0.020) and pTNM stage (HR = 1.706 (1.116-2.607), p = 0.014) were positively correlated with overall survival in matched patients. CONCLUSIONS: Self-expanding metal stents as "a bridge to surgery" are associated with more perineural invasion, a higher recurrence rate and worse overall survival in patients with acute malignant left-sided colonic obstruction compared with emergency surgery.

Chemopreventive effect of 4'-hydroxychalcone on intestinal tumorigenesis in ApcMin mice.

Chalcones and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. However, the in vivo anticancer effects and associated mechanisms of chalcones against intestinal tumorigenesis currently remain unclear. The aim of the present study was to investigate the chemopreventive effect of a chalcone derivative, 4'-hydroxychalcone (4-HC), in a transgenic adenomatous polyposis coli multiple intestinal neoplasia mouse model (ApcMin) of spontaneous intestinal adenomas. ApcMin mice were fed 4-HC (10 mg/kg/day) or the vehicle control by oral gavage starting at 8 weeks of age, and were sacrificed at 20 weeks. The administration of 4-HC significantly decreased the number of colon adenomas by 45% and the size of colon adenomas by 35% compared with the respective controls. Similarly, the number of adenomas in the distal small intestine (DSI) and proximal small intestine also decreased by 35 and 33%, respectively, in 4-HC-treated mice, and adenoma size in the DSI decreased by 39% compared with the respective controls. Treatment with 4-HC strongly decreased proliferation in colon and DSI adenomas, as detected by immunofluorescence staining with the proliferation marker protein Ki-67, and promoted apoptosis in colon adenomas, as detected by TUNEL immunofluorescence staining. In addition, decreased mRNA expression of ß-catenin target genes, including c-Myc, Axin2 and CD44, in colon adenomas of 4-HC-treated animals demonstrated the involvement of the Wnt/ß-catenin signaling pathway in the initiation and progression of colon neoplasms. Treatment with 4-HC also decreased the protein levels of ß-catenin in colon adenomas, as demonstrated by immunofluorescence staining. The results suggested that 4-HC may be a promising candidate for the chemoprevention of intestinal tumorigenesis, and further investigations are required to evaluate its clinical utility.

Comprehensive analysis of differentially expressed circRNAs revealed a ceRNA network in pancreatic ductaladenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. However, the molecular mechanisms underlying PDAC are still not completely understood. Circular RNAs (circRNAs) are a unique class of RNA formed by special loop splicing. More and more researchers have paid attention to circRNAs. MATERIAL AND METHODS: In this study, we constructed a circRNA-mediated competing endogenous RNA (ceRNA) network in PDAC. Gene ontology (GO) analysis was performed to explore circRNAs' potential roles in PDAC progression. We also constructed an up-stream transcriptional network of circRNAs' parental genes and found that many transcription factors (TFs), such as tumor protein p53 (TP53) and MYC, could regulate their expression. RESULTS: This study, which aimed to identify differentially expressed circRNAs in PDAC, suggested that circRNAs may also act as biomarkers for PDAC. We analyzed two public datasets (GSE69362 and GSE79634) to identify differentially expressed circRNAs in PDAC. Finally, we found that DExH-Box Helicase 9 (DHX9) may be a potential regulator of circRNA formation in PDAC. Genomic loci of four down-regulated circRNAs - hsa_circ_000691, hsa_circ_0049392, hsa_circ_0005203, and hsa_circ_0001626 - contained DHX9 binding sites, suggesting that they may be directly regulated by DHX9. CONCLUSIONS: Our study identified differentially expressed circRNAs in PDAC, suggesting that circRNAs may also act as biomarkers for PDAC. Additional investigations of function and up-stream regulation of differentially expressed circRNA in PDAC are still needed.

[Clinical application of compound anastomotic device in protective terminal ileostomy during rectal cancer operation].

OBJECTIVE: To investigate the clinical effect of the application of "compound anastomotic device" on the high-risk colorectal anastomosis in rectal cancer patients undergoing protective ileostomy. METHODS: A total of 116 rectal cancer patients undergoing surgical procedure and prophylactic ileostomy in Tongji Hospital (90 cases) and The Third People's Hospital of Jingdezhen City (26 cases) from May 2011 to October 2016 were prospectively enrolled in the study. Paralleled control study and random digital table were applied. Fifty-eight cases received the compound anastomotic device for protective ileostomy (anastomosis ring group) and 58 cases underwent traditional terminal ileostomy (traditional group). The compound device was mainly composed of Valtrac biodegradable anastomosis ring, drainage tube and condom. Operational procedure was as follows: Ileocecum was freed through incision following laparoscopic total mesorectal excision; Two intestinal ring-shape purses were made; Intestinal wall between purse string was cut and the compound anastomotic device was put into; The purse was tightened and anastomosis ring was closed; The compound device was embed and pull out through the Trocar hole in the right lower abdomen; Then the drainage tube was fixed to the abdominal wall and connected with a drainage bag or an outer pocket. Incidence of anastomotic leak, stoma-related complications, hospital stay and total cost of two groups were compared. RESULTS: The general clinical data between two groups were not significantly different(all P>0.05). Stoma operation was performed successfully in all the patients of two groups. The stoma operation time was (34.6±13.8) min in anastomosis ring group and (25.8±14.0) min in traditional group with significant difference (t=2.123, P=0.035). Postoperative anastomotic leak occurred in 7 cases, including 3 cases with small fistula in traditional group and 4 cases in anastomosis ring group, of whom 1 case underwent left-low abdominal colonic stoma after necrotic intestine resection. All the patients were discharged within postoperative 7 to 37 days. In traditional group, 35 cases (60.3%) occurred stoma-related complications, the total hospitalization expenses was (65±28) thousand yuan, and the average hospital stay (including stoma reversion) was (23.6±11.8) days. In anastomosis ring group, 17 cases (29.3%) occurred stoma-related complications, the total hospitalization expense was (52±11) thousand Yuan, and the average hospital stay was (21.0±16.8) days. The incidence of anastomotic fistula and the hospital stay had no significant difference between two groups (all P>0.05). The stoma-related complication morbidity (χ2=3.216, P=0.002) and the total hospitalization expenses (t=2.683, P=0.027) in anastomosis ring group were significantly lower than those in traditional group. CONCLUSION: Compared with traditional ileostomy, the application of compound anastomotic device for protective ileostomy would be better to benefit the recovery of patients.

Therapeutic inhibition of SGK1 suppresses colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.

Therapeutic Effects of Ischemic-Preconditioned Exosomes in Cardiovascular Diseases.

Despite years of researches, cardiovascular disease (CVD) remains the most common cause of death around the world. Lots of studies showed that by pretreating with short nonfatal ischemia in in situ organ or distant organ, one could develop tolerance to the following fatal ischemia. The process is called ischemic preconditioning (IPC). IPC prepare the heart for damage by producing inflammatory signals, miRNA, neuro system stimulation and exosomes. Among them, exosomes have been gaining increasing interest since it is characterized by its capability to carry information and its specific ligand-receptor system. Here we will discuss IPC induced exosomes and its protective effects during ischemic heart disease.

Therapeutic Suppression of miR-4261 Attenuates Colorectal Cancer by Targeting MCC.

The mutated in colorectal cancer (MCC) gene is an important colorectal tumor suppressor gene, although few studies have reported the microRNA(s) that could directly target MCC in colorectal cancer. Here, we used microRNA (miRNA) target prediction algorithms, and previously reported microarray data in human colorectal cancer found that only miR-4261 was predicted by all three databases to directly target MCC. Based on specimens from our own cohort of colorectal cancer patients, we further demonstrated that miR-4261 was overexpressed in colorectal cancer. Interestingly, overexpression of miR-4261 could enhance cell proliferation and G1/S phase transition of cell cycle, and promote cell migration in HCT116 and HT29 cells, while inhibition of miR-4261 had opposite effects. Luciferase reporter assay and western blot analysis confirmed MCC as a direct target of miR-4261. MCC small interfering RNA (siRNA) could abolish the suppressive effects of miR-4261 inhibitor on cell proliferation and migration in HCT116 and HT29 cell lines. Finally, we showed that therapeutic intervention with lentivirus-based miR-4261 sponge injection could effectively reduce tumor growth and inhibit cell proliferation in colorectal cancer xenograft. Collectively, our study is the first one to unravel the functional role of miR-4261, and it provides strong evidence that inhibition of miR-4261 through targeting of MCC might exert a therapeutic effect for colorectal cancer.

miR-224 Controls Human Colorectal Cancer Cell Line HCT116 Proliferation by Targeting Smad4.

Background: Better understanding the molecular mechanisms responsible for the genesis and progression of colorectal cancer would help advance the novel therapeutics. miR-224 has been identified to be elevated in colorectal cancer and promote human colorectal cancer cell line SW480 proliferation and invasion. However, the effect of miRNAs on cancer cell proliferation could be significantly changeable among different cell lines. HCT116 is a commonly used cell line for colorectal cancer study and the target gene responsible for the function of miR-224 in its proliferation is unclear. Methods: miR-224 expression was determined by quantitative reverse transcription polymerase chain reactions (PCRs) in human colorectal cancer tissues compared with their corresponding matched peritumoral tissues. HCT116 cell viability and cell proliferation were determined by CCK-8, EdU incorporation assays and flow cytometry for cell cycle. Target gene of miR-224 was confirmed by Western blots and siRNA for Smad4. Results: miR-224 was significantly increased by 29.49 fold in colorectal cancer tissues compared with their corresponding matched peritumoral tissues based on 12 colorectal cancer patients. miR-224 mimic significantly increased HCT116 cell viability, EdU positive cells rate, and decreased G1 phase cell population and increased S phase cell population. miR-224 inhibitor had opposite effects. Smad4 could be negatively regulated by miR-224 in HCT116 cells and was responsible for its effects in proliferation. Conclusion: miR-224 mediates HCT116 cell proliferation by targeting Smad4.

Development of a new analog of SGK1 inhibitor and its evaluation as a therapeutic molecule of colorectal cancer.

Colorectal cancer (CRC) is one of the most leading causes of cancer-related death worldwide. The serum and glucocorticoid inducible kinase SGK1 is highly expressed and involved in several tumors. GSK650394, a SGK1 inhibitor, has been proved to be effective in impeding tumor growth in vitro. In this study, we developed a novel analog of GSK650394, and evaluated its effects on CRC cells and tumor growth both in vitro and in vivo. HCT116 cells were treated with a concentration gradient of new developed compounds and cholecystokinin octapeptide (CCK-8) assay was used to calculate the IC50 value of every analog. Cell proliferation analysis was estimated from EdU staining and flow cytometry in vitro, and immunohistochemistry of Ki67 and PCNA in vivo. Cell migration analysis was examined using the transwell assay. In vivo tumor growth was determined in athymic nude mice by injecting the HCT116 cells in the subcutaneous tissue, followed by the injection of QGY-5-114-A. We found that new developed GSK650394 analog QGY-5-114-A has lower IC50 value, and treatment with QGY-5-114-A significantly inhibited CRC cell proliferation and migration in vitro. Besides that, colonic tumor growth was also dramatically restricted by QGY-5-114-A in vivo. In conclusion, pharmacological treatment with QGY-5-114-A impedes CRC tumor cell proliferation, migration and tumor growth.

Therapeutic Inhibition of miR-4260 Suppresses Colorectal Cancer via Targeting MCC and SMAD4.

Dysregulation of microRNAs (miRNAs, miRs) and their putative target genes have been increasingly reported to contribute to colorectal cancer. However, miRNAs that directly target the mutated in colorectal cancer (MCC) gene, a tumor suppressor which is downregulated or inactivated in colorectal cancer, remain largely unknown. By using an array-based miRNA analysis, we identified a group of miRNAs that were dysregulated in human metastatic versus non-metastatic colorectal cancer tissues. One of these miRNAs, miR-4260, was predicted to target MCC in the miRDB database. Results using human HCT116 and HT29 colorectal cancer cell lines showed that miR-4260 mimic enhanced cell proliferation and migration and reduced apoptosis induced by the chemotherapeutic agent 5-fluorouracil while miR-4260 inhibitor had inverse effects. Furthermore, miR-4260 negatively regulated MCC as well as SMAD4 by directly binding to the 3'untranslational region (3'UTR). Using siRNAs targeting MCC or SMAD4, we showed that upregulation of MCC and SMAD4 was essential to mediate the functional roles of miR-4260 inhibitor in colorectal cancer cells. Our in vivo experiments indicated that inhibition of miR-4260 reduced colorectal tumor growth in nude mice subcutaneously implanted with HCT116 cells. Significantly, miR-4260 was increased in human colorectal cancer tissues with simultaneous downregulation of MCC and SMAD4, strongly suggesting the clinical relevance of targeting miR-4260 in the treatment of colorectal cancer. In summary, we identified miR-4260 as a novel oncomiR for colorectal cancer that targets MCC and SMAD4. Inhibition of miR-4260 can, therefore, be a potential therapeutic strategy for colorectal cancer.

Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth.

The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs), as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs-miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p-were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

Multivariate logistic regression analysis of postoperative complications and risk model establishment of gastrectomy for gastric cancer: A single-center cohort report.

BACKGROUND: Reporting of surgical complications is common, but few provide information about the severity and estimate risk factors of complications. If have, but lack of specificity. METHODS: We retrospectively analyzed data on 2795 gastric cancer patients underwent surgical procedure at the Affiliated Hospital of Qingdao University between June 2007 and June 2012, established multivariate logistic regression model to predictive risk factors related to the postoperative complications according to the Clavien-Dindo classification system. RESULTS: Twenty-four out of 86 variables were identified statistically significant in univariate logistic regression analysis, 11 significant variables entered multivariate analysis were employed to produce the risk model. Liver cirrhosis, diabetes mellitus, Child classification, invasion of neighboring organs, combined resection, introperative transfusion, Billroth II anastomosis of reconstruction, malnutrition, surgical volume of surgeons, operating time and age were independent risk factors for postoperative complications after gastrectomy. Based on logistic regression equation, p=Exp∑BiXi / (1+Exp∑BiXi), multivariate logistic regression predictive model that calculated the risk of postoperative morbidity was developed, p = 1/(1 + e((4.810-1.287X1-0.504X2-0.500X3-0.474X4-0.405X5-0.318X6-0.316X7-0.305X8-0.278X9-0.255X10-0.138X11))). The accuracy, sensitivity and specificity of the model to predict the postoperative complications were 86.7%, 76.2% and 88.6%, respectively. CONCLUSIONS: This risk model based on Clavien-Dindo grading severity of complications system and logistic regression analysis can predict severe morbidity specific to an individual patient's risk factors, estimate patients' risks and benefits of gastric surgery as an accurate decision-making tool and may serve as a template for the development of risk models for other surgical groups.