Salidroside alleviates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota.

Dysbiosis causes continuous progress of inflammatory bowel disease (IBD). Herein, we aim to explore whether Salidroside (Sal), which is a major glycoside extracted from Rhodiola rosea L., could ameliorate dextran sulfate sodium (DSS)-induced colitis by modulating the microbiota. Results showed that oral treatment with 15 mg kg-1 of Sal inhibited DSS-induced colitis in mice as evidenced by colon length, histological analysis, disease activity index (DAI) score, and the proportion and number of macrophages in the intestine. The gut microbiota of colitic mice was also partly restored by Sal. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with DSS-treated mice, FM from the Sal-treated donor mice significantly mitigated the symptoms of colitic mice, including reducing the DAI score, alleviating tissue damage, boosting the expression of mucin protein (mucin-2) and tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1), and decreasing M1 macrophages in the gut. It was found that both Sal and FMT affected the structure and abundance of the gut microbiota as reflected by the decreased relative abundance of Turicibacter, Alistipes, Romboutsia and the increased relative abundance of Lactobacillus at the genus level. Moreover, the anti-inflammatory effect of Sal disappeared when the gut microbiota was depleted by antibiotics, demonstrating that Sal alleviated the intestinal inflammation in a gut microbiota-dependent manner. Thus, Sal could be a remarkable candidate as a functional food for colitis.

Salidroside protects mice from high-fat diet-induced obesity by modulating the gut microbiota.

Obesity is a systemic disease with multisystem inflammation associated with gut dysbiosis. Salidroside (SAL) which is a major glycoside extracted from Rhodiola rosea L. has a wide range of pharmacological effects, but the role of gut microbiota in the protective effects of SAL on obesity has not been studied. Herein, we aim to explore whether SAL could ameliorate high-fat diet (HFD)-induced obesity in mice by modulating microbiota. Results showed that oral treatment with SAL alleviated HFD-induced obesity in mice as evidenced by body weight and fat weight. SAL supplementation effectively attenuated fat accumulation, lipid synthesis genes expression, liver inflammation, and metabolic endotoxemia. In addition, SAL treatment alleviated intestinal damage and increased the expression of mucin protein (Mucin-2) and tight junction (TJ) proteins (Occludin and Zonula Occludens-1). 16S rRNA sequencing analysis revealed that the gut microbiota of obese mice was also partly improved by SAL via restoring the microbial community structure and diversity. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with fecal transplantation (FM) from the HFD-treated mice, FM from the SAL-treated mice significantly mitigate the symptoms of obese mice, including decreasing body weight, fat accumulation, and attenuating pathological damage in the gut. Thus, SAL could be a remarkable candidate to prevent obesity.

Laparoscopic surgery contributes to a decrease in short-term complications in surgical ulcerative colitis patients during 2008-2017: a multicenter retrospective study in China.

BACKGROUND/AIMS: The aim of this study was to analyze the chronological changes in postoperative complications in surgical ulcerative colitis patients over the past decade in China and to investigate the potential parameters that contributed to the changes. METHODS: Ulcerative colitis patients who underwent surgery during 2008-2017 were retrospectively enrolled from 13 hospitals in China. Postoperative complications were compared among different operation years. Risk factors for complications were identified by logistic regression analysis. RESULTS: A total of 446 surgical ulcerative colitis patients were analyzed. Fewer short-term complications (24.8% vs. 41.0%, P=0.001) and more laparoscopic surgeries (66.4% vs. 25.0%, P<0.001) were found among patients who received surgery during 2014-2017 than 2008-2013. Logistic regression suggested that independent protective factors against short-term complications were a higher preoperative body mass index (odds ratio [OR], 0.870; 95% confidence interval [CI], 0.785-0.964; P=0.008), laparoscopic surgery (OR, 0.391; 95% CI, 0.217-0.705; P=0.002) and elective surgery (OR, 0.213; 95% CI, 0.067-0.675; P=0.009). The chronological decrease in short-term complications was associated with an increase in laparoscopic surgery. CONCLUSIONS: Our data revealed a downward trend of short-term postoperative complications among surgical ulcerative colitis patients in China during the past decade, which may be due to the promotion of minimally invasive techniques among Chinese surgeons.

Predicting lymph node metastasis and recurrence in patients with early stage colorectal cancer.

Tumor budding (TB), a powerful, independent predictor of colorectal cancer (CRC), is important for making appropriate treatment decisions. Currently, TB is assessed only using the tumor bud count (TBC). In this study, we aimed to develop a novel prediction model, which includes different TB features, for lymph node metastasis (LNM) and local recurrence in patients with pT1 CRC. Enrolled patients (n = 354) were stratified into training and validation cohorts. Independent predictors of LNM and recurrence were identified to generate predictive nomograms that were assessed using the area under the receiver operating characteristic (AUROC) and decision curve analysis (DCA). Seven LNM predictors [gross type, histological grade, lymphovascular invasion (LVI), stroma type, TBC, TB mitosis, and TB CDX2 expression] were identified in the training cohort. LNM, histology grade, LVI, TBC, stroma type, and TB mitosis were independent predictors of recurrence. We constructed an LNM predictive nomogram with a high clinical application value using the DCA. Additionally, a nomogram predicting recurrence-free survival (RFS) was constructed. It presented an AUROC value of 0.944 for the training cohort. These models may assist surgeons in making treatment decisions. In the high-risk group, radical surgery with a postoperative adjuvant chemotherapy was associated with RFS. Postoperative chemotherapy can be better for high-risk patients with pT1 CRC. We showed that TB features besides TBC play important roles in CRC pathogenesis, and our study provides prognostic information to guide the clinical management of patients with early stage CRC.

Mechanisms on chemotherapy resistance of colorectal cancer stem cells and research progress of reverse transformation: A mini-review.

Tumor recurrence and chemotherapy resistance are mainly responsible for poor prognosis in colorectal cancer (CRC) patients. Cancer stem cell (CSC) has been identified in many solid tumors, including CRC. Additionally, CSC cannot be completely killed during chemotherapy and develops resistance to chemotherapeutic drugs, which is the main reason for tumor recurrence. This study reviews the main mechanisms of CSC chemotherapy resistance in CRC, including activation of DNA damage checkpoints, epithelial-mesenchymal transition (EMT), inhibition of the overexpression of antiapoptotic regulatory factors, overexpression of ATP-binding cassette (ABC) transporters, maintenance of reactive oxygen species (ROS) levels, and the dormant state of CSC. Advances in research to reverse chemotherapy resistance are also discussed. Our study can provide the promising potential for eliminating CSC and preventing tumor progression for CRC treatment.

Associations of C-X-C motif chemokine ligands 1/2/8/13/14 with clinicopathological features and survival profile in patients with colorectal cancer.

The present study aimed to assess the correlation of C-X-C motif chemokine ligand (CXCL)1, CXCL2, CXCL8, CXCL13 and CXCL14 with clinicopathological features and survival profile in patients with colorectal cancer (CRC). Patients with primary CRC (n=232) were retrospectively reviewed, with their tumor tissue specimens acquired from the Department of Pathology (The First Hospital of Jilin University, Changchun, China), their demographic data and preoperative tumor features collected from the hospital database, and their survival data obtained from the follow-up documents. Tumor CXCL expression was detected by immunohistochemistry (IHC). Based on the total IHC score, the expression of CXCL1, CXCL2, CXCL8, CXCL13 and CXCL14 was categorized as low expression (IHC score ≤3) and high expression (IHC score >3). CXCL1 (51.3% high and 48.7% low), CXCL2 (59.9% high and 40.1% low), CXCL8 (44.4% high and 55.6% low), CXCL13 (40.9% high and 59.1% low) and CXCL14 (31.0% high and 69.0% low) were expressed in CRC tumor tissues, and their expression levels were correlated with each other, except between CXCL8 and CXCL14, and between CXCL13 and CXCL14. CXCL1 was associated with a larger tumor size, and an advanced T stage, N stage and Tumor-Node-Metastasis (TNM) stage. CXCL2 was associated with an advanced N stage and TNM stage, and CXCL8 was associated with a greater T stage and TNM stage. CXCL13 was associated with a greater T stage, N stage and TNM stage, while CXCL14 was not associated with any clinical characteristics. As for survival, CXCL1, CXCL2, CXCL8 and CXCL13, but not CXCL14, were associated with poor overall survival (OS) rate, and further multivariate Cox's regression model analysis revealed that CXCL1 independently predicted unfavorable OS in patients with CRC. Overall, CXCL1, CXCL2, CXCL8 and CXCL13 have good potential as an indicator for tumor features and survival in patients with CRC.

Association of sleep duration with chronic constipation among adult men and women: Findings from the National Health and Nutrition Examination Survey (2005-2010).

Background: Previous studies suggested that unhealthy sleep patterns were closely associated with gastrointestinal diseases, but the impact of unhealthy sleep duration on chronic constipation has not been well studied until now. In this study, we aim to explore the association between sleep duration and constipation among males and females. Methods: We utilized the US National Health and Nutrition Examination Surveys data from 2005 to 2010, and adults (≥20 years old) who completed the sleep and bowel health questionnaires were enrolled in this observational study. Sleep duration was categorized into four groups: very short sleep (<5 h/night), short sleep (5-6 h/night), normal sleep (7-8 h/night), and long sleep (≥9 h/night). Chronic constipation was defined as Bristol Stool Scale Type 1(separate hard lumps, like nuts) or Type 2(sausage-like but lumpy). Controlling demographic, lifestyle, and dietary factors, the logistic regression model in Generalized Linear Model (GLM) function was used to estimate the correlation of sleep duration with constipation among men and women. Results: Of the 11,785 individuals (51.2% males and 48.8% females), 4.3% of men and 10.2% of women had constipation, respectively. More than half of patients with constipation did not adopt the recommended sleep duration. Compared with normal individuals, male participants with constipation had a higher proportion of shorter sleep duration (41.0 vs. 32.3% in the short sleep group and 6.3 vs. 4.7% in the very short sleep group), and female individuals with constipation had a higher proportion of long sleep duration (12.7 vs. 8.2%). After covariates adjustment, men with short sleep duration (5-6 h/night) correlated with increased odds for constipation (OR:1.54, 95%CI:1.05-2.25), and women with long sleep duration (≥9 h/night) linked to the higher constipation risk (OR:1.58, 95%CI:1.10-2.29). Excessive sleep duration in males or insufficient sleep duration in females was neither linked to increased nor decreased constipation risk. Conclusions: In this observational study of a nationally representative sample of adults, we demonstrate a differential impact of unhealthy sleep duration on constipation among men and women. Short sleep duration poses a higher risk of constipation in men, and excessive sleep duration correlates with higher constipation risk in women.

Modified Perineal Reconstruction Combined with Anal Sphincter Repair for Obstetric Anal Sphincter Injuries.

Objective: The aim of this study was to investigate the clinical effectiveness of modified perineal reconstruction combined with anal sphincter repair in the treatment of obstetric anal sphincter injuries (OASIS). Methods: Twenty consecutive patients with an OASI who underwent modified perineal reconstruction combined with anal sphincter repair in the Department of Colorectal and Anal Surgery of the First Hospital of Jilin University from October 2015 to September 2017 were retrospectively enrolled in this study. Anal function was evaluated using the Williams grade, the Wexner score, anorectal manometry, and transrectal ultrasound. Results: Differences in both the Williams grade and the Wexner score prior to operation and following surgery indicated that anal function had improved, and these differences were statistically significant (P < 0.05). These indices also showed further improvement six months after surgery as compared with values at one month, and again, these differences were statistically significant (P < 0.05). In addition, anorectal manometry at six months following surgery showed statistically significant differences in the maximum anal resting pressure, maximum anal systolic pressure, and anal defecation pressure as compared with values prior to operation (P < 0.05). Postoperative endorectal ultrasound revealed that the anal sphincter presented with close imbricated overlapping. Conclusion: Modified perineal reconstruction combined with anal sphincter repair in the treatment of female perineal defect is associated with a good clinical outcome, strengthening anal function, and reconstructing the perineum, and is a possible method for clinical treatment.

Treating highly complex anal fistula with a new method of combined intraoperative endoanal ultrasonography (IOEAUS) and transanal opening of intersphincteric space (TROPIS).

INTRODUCTION: Treatment of highly complex anal fistula is still a profound test for a specialist colorectal surgeon. The reasons are directly related to recurrence and incontinence. AIM: To evaluate the clinical results of a combined method of intraoperative endoanal ultrasonography (IOEAUS) and transanal opening of the intersphincteric space (TROPIS). MATERIAL AND METHODS: This study retrospectively included 48 patients with complex anal fistula, all of whom underwent new surgical methods. This operation mainly consists of two steps. Firstly, the type of anal fistula was determined by endoanal ultrasonography (EAUS) or magnetic resonance imaging (MRI) before the operation. Then the TROPIS procedure was performed with the help of EAUS, and the decision on whether a drainage seton should be placed depended on the condition of the tract. If there were secondary tracts, they were found and the same was done. RESULTS: The median follow-up was 12 months. Two (4.1%) patients experienced recurrence. Four (8.3%) patients did not have primary healing. All 6 patients underwent the same procedure again, and three recovered completely. So total successful fistula healing was observed in 45 (93.7%). There were no major complications and no significant deterioration in anal function and incontinence postoperatively. CONCLUSIONS: Combined IOEAUS and TROPIS is an effective procedure in the treatment of highly complex anal fistula, and it may offer a new means for other operations.

Bacillus licheniformis Zhengchangsheng® Inhibits Obesity by Regulating the AMP-Activated Protein Kinase Signaling Pathway.

As a metabolic syndrome, obesity has become a global public health problem. Bacillus licheniformis has been shown to inhibit obesity by regulating the gut microbiota, but the underlying mechanism of its therapeutic effect is still unknown. In this study, the anti-obesity mechanism of Bacillus licheniformis Zhengchangsheng® was investigated by examining a high-fat diet-induced obesity mouse model. Our results showed that Bacillus licheniformis Zhengchangsheng® significantly decreased body weight gain and fat accumulation, serum lipid profiles, and proinflammatory cytokine levels and improved glucose and lipid metabolism in obese mice. Furthermore, compared with those of high-fat diet-fed mice, Bacillus licheniformis Zhengchangsheng® treatment also inhibited nuclear factor-κB activation, increased phosphorylated AMP-activated protein kinase activation in the liver, and regulated the expression of genes associated with lipid metabolism. These results indicated that Bacillus licheniformis Zhengchangsheng®-induced obesity inhibition could occur by activating the AMP-activated protein kinase signaling pathway. Thus, our results suggested that Bacillus licheniformis Zhengchangsheng® has the potential to treat obesity and related metabolic diseases in the clinic.

Matrix metalloproteinase-8 rs11225395 polymorphism correlates with colorectal cancer risk and survival in a Chinese Han population: a case-control study.

Matrix metalloproteinase-8 (MMP-8) is a gene associated with inflammation and prognosis in colorectal cancer (CRC). Here, we studied the link between the rs11225395 polymorphism of MMP-8 gene and CRC risk. We recruited 551 CRC cases and 623 controls from among a subpopulation of Han Chinese patients. Data found that this variant was connected to an increased risk of CRC (TT versus CC: OR, 1.76; 95%CI, 1.09-2.84; P = 0.021; T versus C: OR, 1.29; 95%CI, 1.07-1.56; P = 0.007). Stratified analyses indicated a positive association among smokers (TT versus CC: OR, 2.31; 95%CI, 1.12-4.79; P = 0.024), males, and patients ≥ 60 years old. Crossover analysis showed that the potential interaction between smoking or drinking and the MMP-8 rs11225395 polymorphism was related to elevated risk for CRC. The rs11225395 polymorphism was also connected with lymph node metastasis and TNM stage. Moreover, the CRC cases carrying a TT genotype of MMP-8 rs11225395 presented had poorer overall survival than the CC genotype carriers. These findings show that MMP-8 rs11225395 correlates with an elevated risk of CRC and poor patient prognosis in a subpopulation of the Han Chinese subpopulation. Thus, the MMP-8 rs11225395 polymorphism could potentially function as a biomarker predictive of CRC susceptibility.

Long-term hexavalent chromium exposure facilitates colorectal cancer in mice associated with changes in gut microbiota composition.

Colorectal cancer (CRC) is among the leading causes of cancer-related mortality worldwide. Hexavalent chromium [Cr(VI)] is often present in groundwater. Chronic Cr(VI) exposure is suggested to be one of the main factors inducing cancer. However, the correlation between Cr(VI) and CRC remains unclear. In this study, we investigated the role of Cr(VI) in CRC by establishing a mouse CRC model induced by 1, 2-dimethylhydrazine (DMH). The results showed that Cr(VI) increased weight loss in DMH-induced mice and promoted the formation of tumors. Cr(VI) also increased DMH-induced proliferating cell nuclear antigen (PCNA) levels. Investigation of the underlying mechanisms found that Cr(VI) significantly decreased DMH-induced SOD, GSH and CAT levels, while, the MDA level increased. Metagenomic analyses found that the abundance of Firmicutes and Bacteroidetes in the DMH + Cr group was down-regulated. Interestingly, the combination of Cr(VI) and DMH significantly increased the abundance of Verrucomicrobia. At the family and genus levels, families Akkermansiaceae and Saccharimonadaceae and genus Akkermansia were more abundant in the DMH + Cr group, whereas the abundance of short-chain fatty acid (SCFA)-producing bacteria (family Muribaculaceae, family Lachnosipiraceae, genus Lachnospiraceae_NK4A136_group, and genus Roseburia) decreased. These results indicate that Cr(VI) might aggravate CRC by altering the composition of the gut microflora.

Silencing of TMEM158 Inhibits Tumorigenesis and Multidrug Resistance in Colorectal Cancer.

Transmembrane protein 158 (TMEM158) plays pivotal roles in many cancers, including colorectal cancer (CRC). It has been reported that it is a recently identified upregulated gene during Ras-induced senescence. However, the clinical significance and biological functions of TMEM158 in CRC remain largely unknown. In this study, we found that TMEM158 was highly expressed in CRC tissues and cell lines compared with the corresponding noncancerous samples and normal colon epithelial cells. In vitro studies showed that TMEM158 silencing inhibited proliferation, and migration and increased apoptosis of CRC cells, whereas overexpression of TMEM158 increased proliferation, migration, and apoptosis escape of CRC cells. Mechanically, the levels of drug resistance-associated molecules, including multidrug resistance 1 and multidrug resistance protein 1, as well as the expression of antiapoptotic Bcl-2 were significantly upregulated. In addition, TMEM158 knockdown significantly inhibited tumor growth in vivo. Collectively, these results demonstrated that TMEM158 is a significant regulator of tumorigenesis and drug resistance in CRC and provided evidence that TMEM158 may be a promising target for CRC therapy.

The physical activity of colorectal cancer survivors during chemotherapy : Based on the theory of planned behavior.

PURPOSE: The purpose of this study was to investigate the physical activity (PA) of colorectal cancer (CRC) survivors during chemotherapy and to explain it based on the theory of planned behavior (TPB). In addition, the effects of planning, past physical activity (P-PA), and self-efficacy on the PA of CRC survivors were analyzed. METHODS: CRC survivors were recruited in a third-grade hospital of Changchun via a convenience sampling method. All survivors were asked to complete self-report questionnaires assessing medical and demographic variables, PA, constructs from the TPB, P-PA, planning, and self-efficacy. RESULTS: A total of 174 CRC survivors were included in this study. Only 7.5% (13) of these CRC survivors had sufficient PA, and 32.2% (56) of CRC survivors were completely sedentary. Gender, education level, working status, residential location, method of payment for medical expenses, and cancer stage were all associated with PA in these patients (P < 0.05). The path model was able to explain 54% (R2 = 0.54) of the PA variance in these CRC survivors. P-PA had the greatest impact on PA during chemotherapy, and P-PA affected PA both directly and indirectly through planning. CONCLUSIONS: Insufficient PA in CRC survivors was associated with a variety of factors, with P-PA having the greatest impact on this outcome. The results of this study suggest that attention must be paid to survivors who had exhibited insufficient PA prior to initial diagnosis.

The Relationship between Self-Perceived Burden and Posttraumatic Growth among Colorectal Cancer Patients: The Mediating Effects of Resilience.

At present, the influence factors of posttraumatic growth (PTG) in colorectal cancer (CRC) patients and the relationship between PTG, self-perceived burden (SPB), and resilience are not completely clear. Thus, the present study examined whether resilience and SPB could predict PTG in CRC patients. The role of resilience as a potential mediator was also assessed. Using a cross-sectional design, a convenience sample of 157 CRC patients was selected as subjects, from July to December 2016 in a third-grade hospital. It was found that the main influencing factors for the total PTG score of CRC patients included work status, affordability for medical expenses, and duration of illness. Resilience was positively correlated with PTG, SPB was negatively correlated with PTG, and resilience played an intermediary role. Our findings remind clinicians to treat the psychosocial response of CRC patients from multiple perspectives, with a focus on their positive aspects. By increasing resilience and reducing the patient's SPB, clinicians might enhance the patient's PTG and quality of life.

ZNF280A Promotes Proliferation and Tumorigenicity via Inactivating the Hippo-Signaling Pathway in Colorectal Cancer.

Aberrant expression of zinc-finger proteins has been extensively reported to contribute to malignant progression in a variety of cancers. However, clinical significance and biological roles of ZNF280A in the field of cancer are poorly known. In this study, the expression of ZNF280A was detected in clinical colorectal cancer (CRC) tissues. Functional experiments in vitro and animal experiment in vivo were performed to measure the effect of ZNF280A on the proliferation and tumorigenesis in CRC cells. Western blot and luciferase assays were used to identify the underlying pathway mediating the biological roles of ZNF280A in CRC. Here we report that ZNF280A was upregulated in CRC tissues and cells and a high expression of ZNF280A correlated with tumor, lymph node, and metastasis (TNM) classifications, clinical stage, and predicted poor prognosis and disease progression in CRC patients. Moreover, silencing ZNF280A repressed proliferation and induced G0 and/or G1 arrest in vitro, and it inhibited tumorigenesis of CRC cells in vivo. Our results further demonstrate that silencing ZNF280A inhibited the proliferation of CRC cells by activating Hippo signaling. Therefore, our results uncover a novel mechanistic understanding of ZNF280A-mediated tumor progression in CRC, and meanwhile they provide a novel prognostic factor in CRC patients and a potential therapeutic target for the treatment of CRC.

Chlorogenic Acid Ameliorates Lead-Induced Renal Damage in Mice.

Lead (Pb) exposure is a global environmental problem and its exposure can lead to serious renal damage by disturbing the pro-oxidant/antioxidant balance and facilitating inflammation. Chlorogenic acid (CGA) is one of the most abundant polyphenols in the diet and has been reported to have many biological properties such as antioxidant and anti-inflammatory. In this study, we aimed to investigate the protective efficacy and mechanism of CGA against Pb-induced nephrotoxicity in mice. The results showed that CGA inhibited Pb-induced bodyweight loss, reduced kidney coefficients, and alleviated renal function and structure. Exploration on the potential mechanism demonstrated that CGA suppressed Pb-induced inflammation in the kidney by regulating NF-κB pathway activation. Furthermore, CGA significantly increased Pb-induced reduction in the activity of SOD and GSH-Px, and reduced Pb-induced increase in the content of MDA. The expression of Bax and Bcl-2 associated with apoptosis was also significantly regulated by CGA. These data indicated that CGA may play a potential treatment strategy for Pb toxicity.

ATAD2 silencing decreases VEGFA secretion through targeting has-miR-520a to inhibit angiogenesis in colorectal cancer.

ATPase family AAA domain-containing protein 2 (ATAD2) is involved in various types of cancers, including colorectal cancer. This study aimed to determine the role of ATAD2 in angiogenesis in colorectal cancer. Here, we downregulated ATAD2 expression in HCT116 and SW480 cells, and collected the conditioned medium (CM) from control and ATAD2-silenced cells. The effect of CM on human umbilical vein endothelial cells (HUVEC) was evaluated by using CCK-8, wound healing, tube formation, Western blot, and dual-luciferase reporter assays. Our results showed that the proliferation, migration, and tube formation of HUVEC were reduced in presence of ATAD2-silenced CM, and the levels of phosphorylated vascular endothelial growth factor receptor 2 (P-VEGFR2), CD31, and CD34 were downregulated. Mechanism studies showed that ATAD2 silencing regulated the expression of vascular endothelial growth factor A (VEGFA) and miR-520a. Moreover, we found that miR-520a could bind to ATAD2, and its inhibitor partly reversed the alterations in HUVEC induced by CM from ATAD2-silenced cells. In addition, we demonstrated that miR-520a directly bound to 3'-UTR of VEGFA and inhibited its expression. Collectively, our results indicate that ATAD2 inhibition suppresses VEGFA secretion by increasing miR-520a levels. Our study suggests ATAD2 as a potential therapeutic target for angiogenesis in colorectal cancer.

TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway.

BACKGROUND: Aberrant expression of transcription Factor AP-2 Gamma (TFAP2C) has been reported to be implicated in malignant process of many cancers. The purpose of this study is to investigate the clinical significance and biological roles of TFAP2C in colorectal cancer (CRC). METHODS: TFAP2C expression was evaluated by real-time PCR, Western blot and immunohistochemistry (IHC) respectively in clinical CRC tissues. Statistical analysis was performed to explore the correlation between TFAP2C expression and clinicopathological features, and overall and progression-free survival in CRC patients. In vitro and in vivo assays were performed to assess the biological roles of TFAP2C in CRC cells. Western blot, luciferase and Chromatin immunoprecipitation (ChIP) assays were used to identify the underlying pathway mediating the biological roles of TFAP2C in CRC. RESULTS: TFAP2C is robustly upregulated in CRC tissues and cells, and high expression of TFAP2C correlates with advanced clinicopathological features, poor prognosis and disease progression in CRC patients. Furthermore, upregulating TFAP2C enhances spheroids formation ability, the fraction of SP cells, expression of stem cell factors and the mitochondrial potential, and reduces the apoptosis induced by 5-fluorouracil in colorectal cancer cells in vitro, and promotes stemness and chemoresistance of CRC cells in vivo; while silencing TFAP2C yields an opposite effect. Importantly, downregulation of TFAP2C dramatically restores chemotherapeutic sensitivity of CRC cells to 5-FU in vivo. Our results further demonstrate that TFAP2C promotes stemness and chemoresistance of CRC cells to 5-FU by inhibiting Hippo signaling via transcriptionally upregulating ROCK1 and ROCK2 in CRC cells. CONCLUSION: Our findings indicate that TFAP2C may serve as a novel prognostic factor in CRC patients, and a therapeutic target for the treatment of CRC, suggesting that silencing TFAP2C in combination with 5-FU may be an effective therapeutic strategy to improve survival in CRC patients.

Ganoderic acid A inhibits proliferation and invasion, and promotes apoptosis in human hepatocellular carcinoma cells.

Ganoderic acid A (GA­A), a triterpenoid, has been demonstrated to suppress cell proliferation in various cancers, including breast cancer and osteosarcoma. However, its effect on human hepatocellular carcinoma (HCC) remains to be elucidated. The present study aimed to investigate the effect of GA­A on HCC cells in vitro. The HepG2 and SMMC7721 human HCC cell lines were treated with differing concentrations of GA­A for 24, 48 and 72 h. The cell growth rate, cell cycle and apoptosis, migration and invasion were determined using a Cell Counting Kit­8, flow cytometry and transwell assays, respectively. The expression of apoptosis­associated proteins was detected via western blot analysis. GA­A significantly inhibited the proliferation of human HCC HepG2 and SMMC7721 cells in a dose­dependent manner. Furthermore, GA­A induced cell cycle arrest at the G0/G1 phase and apoptosis, and suppressed the migration and invasion of HCC cells. Furthermore, GA­A decreased the expression of cyclin D1 and increased the expression of p21 and cleaved caspase­3. In conclusion, GA­A suppressed the proliferation of human HCC cells in vitro and may act as a promising natural therapeutic reagent in the treatment of HCC.