Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

OBJECTIVE: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. MATERIAL AND METHODS: In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. RESULTS: Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. CONCLUSIONS: TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome.

Serotonin (5-HT) and the serotonin transporter (SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome (IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mRNA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microRNAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.

Clinical features of upper gastrointestinal serrated lesions: An endoscopy database analysis of 98746 patients.

AIM: To analyse the clinical features of patients with the serrated lesions in the upper gastrointestinal tract (UPGI) tract. METHODS: Patients who underwent routine esophagogastroduodenoscopy (EGD) at the Digestive Endoscopy Centre of General Hospital, Tianjin Medical University between January 2011 and December 2015 were consecutively recruited. Patients with UPGI serrated lesions were consecutively identified. The patients' demographics and histopathology were recorded. The colorectal findings for patients who underwent colonoscopy simultaneously or within six months were also extracted from the colonoscopy database. In addition, we analysed differences in colorectal neoplasia detection between the study patients and randomly selected patients matched for age and gender who did not exhibit serrated lesions and who also underwent colonoscopy in the same period. RESULTS: A total of 21 patients out of 98746 patients (0.02%) who underwent EGD were confirmed to have serrated lesions with predominantly crenated, sawtooth-like configurations. The mean age of the 21 patients was (55.3 ± 17.2) years, and 11 patients were male (52.4%). In terms of the locations of the serrated lesions, 17 were found in the stomach (including 3 in the cardia, 9 in the corpus and 5 in the antrum), 3 were found in the duodenum, and 1 was found in the esophagus. Serrated lesions were found in different mucosal lesions, with 14 lesions were detected in polyps (8 hyperplastic polyps and 6 serrated adenomas with low grade dysplasia), 3 detected in Ménétrier gastropathy, 3 detected in an area of inflammation or ulcer, and 1 detected in the intramucosal carcinoma of the duodenum. In addition, colonoscopy data were available for 18 patients, and a significantly higher colorectal adenoma detection rate was observed in the UPGI serrated lesions group than in the randomly selected age- and gender-matched group without serrated lesions who also underwent colonoscopy in the same period (38.9% vs 11.1%, OR = 5.091, 95%CI: 1.534-16.890, P = 0.010). The detection rate of advanced adenoma was also higher in the UPGI serrated lesions group (22.2% vs 4.2%, OR = 6.571, 95%CI: 1.322-32.660, P = 0.028). CONCLUSION: Serrated lesions in the UPGI were detected in various mucosal lesions with different pathological morphologies. Moreover colonoscopy is recommended for the detection of concurrent colorectal adenoma for these patients.

Detection Rate, Distribution, Clinical and Pathological Features of Colorectal Serrated Polyps.

BACKGROUND: Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western countries. However, few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic populations. The aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic population. METHODS: Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were analyzed. Chi-square test or Fisher's exact test and logistic regression analysis were used for the data processing. RESULTS: A total of 9191 (31.7%) patients were detected with at least one colorectal polyp. The prevalence of serrated polyps was 0.53% (153/28,981). The proportions of hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) of all serrated polyps were 41.2%, 7.2%, and 51.6%, respectively, which showed a lower proportion of HP and SSA/P and a higher proportion of TSA. Serrated polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and age. The proportions of large and proximal serrated polyps were 13.7% (21/153) and 46.4% (71/153), respectively. In total, 98.9% (89/90) serrated adenomas were found with dysplasia. Moreover, 14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia, and large serrated polyps (LSPs) (odds ratio: 3.446, 95% confidence interval: 1.010-11.750, P < 0.05), especially large HPs, might have an association with synchronous advanced neoplasia (AN). CONCLUSIONS: The overall detection rate of colorectal serrated polyps in Chinese symptomatic patient population was low, and distribution pattern of three subtypes is different from previous reports. Moreover, LSPs, especially large HPs, might be associated with an increased risk of synchronous AN.

Fecal microbiota transplantation broadening its application beyond intestinal disorders.

Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.