Zhe Yang

Candidate microRNA biomarkers in human colorectal cancer: Systematic review profiling studies and experimental validation†

Colorectal cancer (CRC) is a major cause of cancer mortality worldwide. There is an urgent need to search for specific and sensitive biomarkers for early diagnosis of CRC. We carried out a comprehensive systematic review of published studies that compared the miRNA expression profiles between CRC tissue and paired neighboring noncancerous colorectal tissue to determine candidate miRNA biomarkers for CRC. A miRNA ranking system that takes the number of comparisons in agreement, total study sizes and direction of differential expression into the consideration was devised and used. One of the most up‐regulated miRNAs, miRNA‐106a, was consistently reported to be differentially expressed in six studies and the five most down‐regulated miRNAs, miR‐30a‐3p, miR‐139, miR‐145, miR‐125a and miR‐133a, were consistently reported to be differentially expressed in four studies. Moreover, we further validated five miRNAs in a clinical setting using qRT‐PCR, which demonstrated that miR‐106a expression was increased, whereas the expression of miR‐30a‐3p, miR‐145, miR‐125a and miR‐133a was decreased in the CRC tissues. Therefore, these miRNAs may be the candidates to develop a panel of biomarkers with sufficient sensitivity and specificity for the diagnosis of CRC in a clinical setting.

Randomised clinical trial: the effects of perioperative probiotic treatment on barrier function and post-operative infectious complications in colorectal cancer surgery – a double-blind study

Aliment Pharmacol Ther 2011; 33: 50–63

Long non-coding RNA CCAL regulates colorectal cancer progression by activating Wnt/β-catenin signalling pathway via suppression of activator protein 2α

Objective Long non-coding RNAs (lncRNAs) are emerging as key molecules in cancers, yet their potential molecular mechanisms are not well understood. The objective of this study is to examine the expression and functions of lncRNAs in the development of colorectal cancer (CRC). Methods LncRNA expression profiling of CRC, adenoma and normal colorectal tissues was performed to identify tumour-related lncRNAs involved in colorectal malignant transformation. Then, we used quantitative reverse transcription PCR assays to measure the tumour-related lncRNA and to assess its association with survival and response to adjuvant chemotherapy in 252 patients with CRC. The mechanisms of CCAL function and regulation in CRC were examined using molecular biological methods. Results We identified colorectal cancer-associated lncRNA (CCAL) as a key regulator of CRC progression. Patients whose tumours had high CCAL expression had a shorter overall survival and a worse response to adjuvant chemotherapy than patients whose tumours had low CCAL expression. CCAL promoted CRC progression by targeting activator protein 2α (AP-2α), which in turn activated Wnt/β-catenin pathway. CCAL induced multidrug resistance (MDR) through activating Wnt/β-catenin signalling by suppressing AP-2α and further upregulating MDR1/P-gp expression. In addition, we found that histone H3 methylation and deacetylases contributed to the upregulation of CCAL in CRC. Conclusions Our results suggest that CCAL is a crucial oncogenic regulator involved in CRC tumorigenesis and progression.

Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130

MicroRNAs (miRNAs) are essential for regulating normal embryonic development and carcinogenesis. Here we report that miR-17-5p, an oncofoetal miRNA, is a key regulator of colorectal cancer progression. We show that miR-17-5p is an oncogenic miRNA that regulates tumorigenesis and progression by targeting the gene encoding P130 and subsequently activating the Wnt/β-catenin pathway. Using specimens from two large cohorts of colorectal cancer patients, we found that patients whose tumours had high miR-17-5p expression had shorter overall survival rates but showed a better response to adjuvant chemotherapy than did patients whose tumours had low miRNA expression. We also observed a strong inverse correlation between miR-17-5p and P130 expression. The current findings suggest that miR-17-5p is a crucial determinant of colorectal cancer progression.

Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB.

Although epithelial barrier dysfunction in the gut has been extensively reported in ulcerative colitis (UC), the pathogenesis of this disease is not completely understood. In the present study, we investigated the role of miR-21 in regulating intestinal epithelial barrier function in UC. Colonic biopsies were obtained from 30 chronic UC patients and 30 healthy controls. Using real-time quantitative polymerase chain reaction (qRT-PCR), we found that both the mucosal and serum levels of miR-21 were upregulated in UC. In situ hybridization (ISH) analysis confirmed the accumulation of miR-21 in UC epithelia cells in vivo. Immunohistochemistry, Western Blot, qRT-PCR, and ultrastructural analyses further demonstrated that the overexpression of miR-21 in UC mucosa and Caco-2 cells impaired the integrity of the tight junctions, resulted in a decrease of the transepithelial electrical resistance (TER) and an increase of the inulin permeability. Furthermore, miR-21 induced the degradation of RhoB mRNA, which led to the depletion of RhoB and the impairment of tight junctions in intestinal epithelial cells.

The relationship between early embryo development and tumourigenesis

•  Introduction •  Embryonic origin of cancer ‐  Early embryo development and tumourigenesis •  Similarity in cell invasive behaviours •  Similarity in epigenetic regulation •  Similarity in gene expression •  Similarity in protein profiling •  Similarity in other biological behaviours •  Conclusion

The effect of perioperative probiotics treatment for colorectal cancer: short-term outcomes of a randomized controlled trial

This study was designed to mainly evaluate the anti-infective effects of perioperative probiotic treatment in patients receiving confined colorectal cancer (CRC) respective surgery. From November 2011 to September 2012, a total of 60 patients diagnosed with CRC were randomly assigned to receive probiotic (n = 30) or placebo (n = 30) treatment. The operative and post-operative clinical results including intestinal cleanliness, days to first - flatus, defecation, fluid diet, solid diet, duration of pyrexia, average heart rate, length of intraperitoneal drainage, length of antibiotic therapy, blood index changes, rate of infectious and non-infectious complications, postoperative hospital stay, and mortality were investigated. The patient demographics were not significantly different (p > 0.05) between the probiotic treated and the placebo groups. The days to first flatus (3.63 versus 3.27, p = 0.0274) and the days to first defecation (4.53 versus 3.87, p = 0.0268) were significantly improved in the probiotic treated patients. The incidence of diarrhea was significantly lower (p = 0.0352) in probiotics group (26.67%, 8/30) compared to the placebo group (53.33%, 16/30). There were no statistical differences (p > 0.05) in other infectious and non-infectious complication rates including wound infection, pneumonia, urinary tract infection, anastomotic leakage, and abdominal distension. In conclusion, for those patients undergoing confined CRC resection, perioperative probiotic administration significantly influenced the recovery of bowel function, and such improvement may be of important clinical significance in reducing the short-term infectious complications such as bacteremia.

Neoadjuvant chemotherapy with a combination of docetaxel, cisplatin, fluorouracil, and leucovorin in nonresectable advanced gastric cancer: a short communication

The aim of this study was to evaluate the efficacy and toxicity of docetaxel (TAX), cisplatin (CDDP), and fluorouracil (5-FU) plus leucovorin (CF) as the neoadjuvant chemotherapy (NACT) regimens in the treatment of nonresectable advanced gastric cancer. Twelve patients with nonresectable advanced gastric cancer were treated with NACT regimens consisted of docetaxel, cisplatin, fluorouracil, plus leucovorin before operation. Nine of the 12 patients were downstaged and 8 were radically operated after the end of the NACT. The overall response rate was 75% with 8.3% complete response and 66.7% partial response, and the ascites disappeared in 63.6%. The most common toxicities were bone marrow suppression, nausea, vomiting, alopecia, and heptoses. The toxicities were recoverable after symptomatic treatment. The results confirmed that the combination of docetaxel, cisplatin, fluorouracil plus leucovorin (CF) is a very effective and well-tolerated regimen as NACT for the patients with nonresectable advanced gastric cancer.