Comparison of specimen extraction site and another site for protective loop ileostomy in laparoscopic low anterior rectal resection: a retrospective comparative study.

BACKGROUND: Protective loop ileostomy is commonly performed in laparoscopic low anterior rectal resection to prevent the serious complications of anastomotic fistula. It is usually created at the right lower quadrant of the abdomen and another wound is required for stoma. The study aimed to evaluate the outcomes of ileostomy at the specimen extraction site (SES) and another site (AS) beside the auxiliary incision. METHODS: A retrospective analysis was conducted on 101 eligible patients with pathologically diagnosed adenocarcinoma of the rectum from January 2020 to December 2021 in the study center. According to whether the ileostomy was at the specimen extraction site, patients were divided into SES group (40 patients) and AS group (61 patients). Clinicopathological characteristics, the intraoperative details, and postoperative outcomes of the two groups were measured. RESULTS: Univariate analysis showed that the operative time was significantly shorter and the blood loss was significantly less in the SES group than in the AS group during laparoscopic low anterior rectal resection, the time to first flatus was significantly shorter, and the pain was significantly less in the SES group than in the AS group during ileostomy closure. The postoperative complications were similar in both groups. Multivariable analysis showed that ileostomy at the specimen extraction site was a significant factor influencing the operative time and blood loss of rectal resection, and influencing the pain and the time to first flatus during ileostomy closure. CONCLUSION: Compared to ileostomy at AS, protective loop ileostomy at SES was time-saving and less bleeding during laparoscopic low anterior rectal resection, and more quick to first flatus and less pain during stoma closure, and did not lead to more postoperative complications. The median incision of the lower abdomen and the left lower abdominal incision were both good sites for ileostomy.

Fibroblast growth factor receptor-like-1: a new therapeutic target and unfavorable prognostic indicator for rectal adenocarcinoma.

Fibroblast growth factor receptor-like-1 (FGFRL1) is important to cell motility and links with tumorigenic potential in various types of cancers. To investigate the biological function and underlying mechanism of FGFRL1 in rectal adenocarcinoma, we conducted this study. TCGA and Oncomine databases were used to analyze FGFRL1 expression and its association with clinical characteristics or overall survival (OS) in rectal adenocarcinoma patients. siRNA strategy was implemented to knockdown FGFRL1 expression in rectal adenocarcinoma cells. CCK8, colony formation, wound healing, and transwell assays were implemented to measure cell behaviors. qRT-PCR and western blot were utilized to identify mRNA and protein expression levels. FGFRL1 was significantly increased in rectal adenocarcinoma tissue samples, either colon or rectum. High-regulation of FGFRL1 expression induced poorer outcome of rectal adenocarcinoma patients. Downregulation of FGFRL1 inhibited the proliferation, colony formation, migration, and invasion of SW837 cells. The MAPK pathway-related proteins, phosphorylation of MEK and ERK, were also decreased after si-FGFRL1 transfection. These findings demonstrated that FGFRL1, acting as a potential inducator, may promote the progression of rectal adenocarcinoma via activating the MAPK signaling pathway.

MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism.

BACKGROUND: Recent studies have indicated the possible function of miR-217 in tumorigenesis. However, the roles of miR-217 in colorectal cancer (CRC) are still largely unknown. METHODS: We examined the expression of miR-217 and AEG-1 in 50 CRC tissues and the corresponding noncancerous tissues by qRT-PCR. The clinical significance of miR-217 was analyzed. CRC cell lines with miR-217 upregulation and AEG-1 silencing were established and the effects on tumor growth in vitro and in vivo were assessed. Dual-luciferase reporter gene assays were also performed to investigate the interaction between miR-217 and AEG-1. RESULTS: Our data demonstrated that miR-217 was significantly downregulated in 50 pairs of colorectal cancer tissues. MiR-217 expression levels were closely correlated with tumor differentiation. Moreover, decreased miR-217 expression was also associated with shorter overall survival of CRC patients. MiR-217 overexpression significantly inhibited proliferation, colony formation and invasiveness of CRC cells by promoting apoptosis and G0/G1 phase arrest. Interestingly, ectopic miR-217 expression decreased AEG-1 expression and repressed luciferase reporter activity associated with the AEG-1 3'-untranslated region (UTR). AEG-1 silencing resulted in similar biological behavior changes to those associated with miR-217 overexpression. Finally, in a nude mouse xenografted tumor model, miR-217 overexpression significantly suppressed CRC cell growth. CONCLUSIONS: Our findings suggest that miR-217 has considerable value as a prognostic marker and potential therapeutic target in CRC.

Evaluation of the seventh AJCC TNM staging system for gastric cancer: a meta-analysis of cohort studies.

The AJCC seventh edition TNM classification for gastric cancer was released in 2010 and included major revision. Large-volume gastric cancer centers have evaluated the prognostic significance of the new system and obtained paradoxical results. The authors performed a meta-analysis of these studies to evaluate the new classification. Fifteen eligible studies with 38,972 patients were included in the analysis. Hazard ratios (HRs) and associated 95 % confidence intervals were extracted from identified studies. The primary outcome was overall survival. The HRs for the seventh edition T classification and N classification were found to increase steadily and reasonably. The cumulative survival rates of the seventh edition subgroups of T classifications demonstrated obvious differences; meanwhile, the differences between subgroups of N classifications including N3a and N3b categories were also significant. The 5-year survival rates according to the seventh edition TNM staging system were 94.71 % (stage IA), 88.72 % (stage IB), 80.45 % (stage IIA), 67.24 % (stage IIB), 53.68 % (stage IIIA), 37.56 % (stage IIIB), and 21.26 % (stage IIIC), respectively. The results of this study indicate that the seventh edition of the TNM classification was considered valid, although further evaluation was needed for N3a and N3b categories.

Expression QTL-based analyses reveal the mechanisms underlying colorectal cancer predisposition.

Genome-wide association studies have identified many risk loci associated with colorectal cancer. Strategies integrating biological data sets with GWAS results will provide insights into the roles of risk single-nucleotide polymorphisms. We performed expression quantitative trait locus-based analyses using the information provided in The Cancer Genome Atlas. Analysis of the cis-expression quantitative trait loci (eQTLs) of 18 previously reported colorectal cancer risk loci resulted in the discovery of five variants that were significantly associated with gene expressions. Analysis of the trans-eQTLs identified three risk loci that affect the expression levels of a neighboring transcription factor, MYC. These findings provide a more comprehensive picture of gene expression determinants in colorectal cancer and insights into the underlying biology of risk loci.

Association between periodic variation of air temperature, humidity, atmospheric pressure and hospital admissions for acute occlusive mesenteric ischaemia.

Referring to the intestinal ischemic injury caused by sudden interruption of the blood supply, acute mesenteric ischemia (AMI) is a highly fatal emergency with mortality rates varying from 58 to 80%. The aim of this study was to explore the effect of temperature on AMI admission. This was a retrospective, multicentric study. The medical records of 1477 patients with verified AMI who were consecutively admitted to 3 hospitals anytime between January 2010 and December 2020 were included in the study. Distributed lag non-linear model was applied, the model was adjusted for temperature, atmospheric pressure, relative humidity, year, holiday, day of the week, time and seasonality. AMI exhibited obvious sex preference, AMI patients tended to be male (M/F ratio = 2.3:1) and in their late 50 s. Hospital admissions of acute mesenteric arterial thromboembolism (AMAT) increased significantly with high temperatures on day of exposure and lag 0-14 day. The effect curve of daily average temperature on acute mesenteric venous thromboembolism (AMVT) admission was J-shaped, and the duration of cold effect was longer, while the duration of heat effect was shorter. An increase in hospital admissions of AMVT was found above 20 °C at lag 0-30. For the first time, our study indicated that temperature is significantly associated with the risk of AMI. Although it is not possible to always avoid exposure to extreme temperatures, one should be aware of dramatic temperature fluctuations and take appropriate precautions.

A comparison between the seventh and sixth editions of the American Joint Committee on Cancer/International Union Against classification of gastric cancer.

OBJECTIVE: To evaluate the prognostic significance of the seventh edition TNM staging classification for gastric cancer. BACKGROUND: The seventh edition TNM staging system for gastric cancer was adopted by the American Joint Committee on Cancer/International Union Against Cancer on January 1, 2010, and included major revisions. METHODS: The authors analyzed data retrospectively collected on patients with gastric cancer who underwent surgery at the Affiliated Hospital of Qingdao University Medical College between 2000 and 2008. A total of 964 patients with gastric cancer who underwent R0 surgical resection were included. RESULTS: The relative risk (RR) for the seventh edition T classification was found to increase steadily and reasonably compared with the sixth edition. However, the RR for the sixth edition N classification was found to increase steadily and reasonably compared with the seventh edition classification. Cox regression multivariate analysis showed that the sixth edition N classification was superior to the seventh edition N classification as an independent prognostic factor. In survival analysis, the seventh edition TNM classification provided a more detailed classification; however, some subgroups of the seventh edition TNM classification did not demonstrate significantly different survival rates. The combination of the seventh edition T classification and the sixth edition N classification, with ideal RR results, showed significantly different survival rates except for IA and IB. CONCLUSIONS: The combination of the seventh edition T classification and the sixth edition N classification seems to provide the optimal prognosis.

The evaluation of metastatic lymph node ratio staging system in gastric cancer.

BACKGROUND: To evaluate the prognostic value and staging accuracy of the metastatic lymph node ratio (rN) staging system for gastric cancer. METHODS: A total of 1,075 patients with gastric cancer who underwent curative surgery between 2000 and 2009 at our institute were analyzed. Lymph node status was assigned according to the American Joint Committee on Cancer (AJCC) pN system and rN system. Patients with >15 (group 1, n = 691) and ≤15 lymph nodes (group 2, n = 384) retrieved were analyzed separately. RESULTS: The rN staging system was generated using 0.2 and 0.5 as the cutoff values of lymph node ratio and then compared with AJCC pN stages. A linear regression model revealed that the number of retrieved lymph nodes was related to the number of metastatic lymph nodes, but not with rN. After a median follow-up of 47.66 months, the 5-year survival rates of N0, N1, N2, and N3 patients of group 1 were significantly better than group 2, whereas the differences were not obvious in the rN classification. CONCLUSIONS: The rN category is a better prognostic tool than the AJCC pN category for gastric cancer patients after curative surgery regardless of the number of lymph node examined.

Circular RNA circPFKP suppresses the proliferation and metastasis of gastric cancer cell via sponging miR-644 and regulating ADAMTSL5 expression.

The treatment of gastric cancer (GC) is extremely challenging; however, the specific pathogenesis of GC remains unclear. Circular RNAs (CircRNAs) are non-coding RNAs that can regulate gene expression both transcriptionally and post-transcriptionally. However, little is known about the circRNAs that are important in the progression of GC. This study identified significantly dysregulated circRNAs by analyzing gastric cancer patients and normal control tissues. The target gene was predicted using online bioinformatics tools and verified using RNA pull-down and luciferase reporter assays. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to evaluate gene and protein expression. The malignant behavior of GC cells was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, wound healing assay, Transwell invasion assay, and flow cytometry. CircPFKP is downregulated in GC tissues, and overexpression of circPFKP inhibits malignant behavior in GC cells. Bioinformatics predicted that circPFKP could bind to miR-644, and miR-644 could target disintegrin-like and metalloprotease domain-containing thrombospondin type 1 motif-like 5 (ADAMTSL5). Overexpression of circPFKP enhances the expression of ADAMTSL5 by decreasing the expression of miR-644 to suppress the growth of xenograft GC tumors in vivo and in vitro. In conclusion, the circPFKP/miR-644/ADAMTSL5 regulatory pathway inhibited the malignant progression of GC. These findings may extend our understanding of the effects of circRNAs on cancer development and provide novel targets for the diagnosis of GC.

CCDC12 promotes tumor development and invasion through the Snail pathway in colon adenocarcinoma.

Integrative expression Quantitative Trait Loci (eQTL) analysis found that rs8180040 was significantly associated with Coiled-coil domain containing 12 (CCDC12) in colon adenocarcinoma (COAD) patients. Immunohistochemical staining and western blotting confirmed CCDC12 was highly expressed in COAD tissues, which was consistent with RNA-Seq data from the TCGA database. Knockdown of CCDC12 could significantly reduce proliferation, migration, invasion, and tumorigenicity of colon cancer cells, while exogenous overexpression of CCDC12 had the opposite effect. Four plex Isobaric Tags for Relative and Absolute Quantitation assays were performed to determine its function and potential regulatory mechanism and demonstrated that overexpression of CCDC12 would change proteins on the adherens junction pathway. Overexpressed Snail and knocked down CCDC12 subsequently in SW480 cells, and we found that overexpression of Snail did not significantly change CCDC12 levels in SW480 cells, while knockdown of CCDC12 reduced that of Snail. CCDC12 plays a significant role in tumorigenesis, development, and invasion of COAD and may affect the epithelial to mesenchymal transformation process of colon cancer cells by regulating the Snail pathway.

Role of Gut Microbiome and Microbial Metabolites in Alleviating Insulin Resistance After Bariatric Surgery.

Insulin resistance (IR) is the most common pathophysiological change in patients with type 2 diabetes mellitus (T2DM). Several recent studies have suggested that the gut microbiome and microbial metabolites are involved in the pathogenesis of IR. Bariatric surgery, as an effective treatment for T2DM, can markedly alleviate IR through mechanisms that have not been elucidated. In this review, we summarize the current evidence on the changes in the gut microbiome and microbial metabolites (including lipopolysaccharide, short-chain fatty acids, branched-chain amino acids, aromatic amino acids, bile acids, methylamines, and indole derivatives) after bariatric surgery. Additionally, we discuss the mechanisms that correlate the changes in microbial metabolites with the postoperative alleviation of IR. Furthermore, we discuss the prospect of bariatric surgery as a treatment for T2DM.

One-stitch method vs. traditional method of protective loop ileostomy for rectal cancer: the impact of BMI obesity.

PURPOSE: Protective loop ileostomy is an effective diversion measure often used to reduce the risk of anastomotic leakage. The purpose of the present study was to evaluate the surgical outcomes of the one-stitch method (OM) of protective loop ileostomy in laparoscopic low anterior resection for BMI obesity patients with rectal cancer compared with the traditional method (TM). METHODS: The patients diagnosed as rectal adenocarcinoma cases by preoperative pathology were included in this retrospective study. The subjects underwent protective loop ileostomy in laparoscopic low anterior resection from January 2016 to June 2019 in the Shandong Provincial Hospital affiliated to Shandong University. The data of loop ileostomy and stoma closure operation were retrieved from the medical cases system of the hospital. RESULTS: 242 patients were included in the present study. In the BMI obese cohort, the OM group showed a shorter operative time both in the loop ileostomy (232.5 vs. 250.0 min, p = 0.04) and stoma closure operation (102.5 vs. 115.0 min, p = 0.001) and a lower peristomal adhesion extent (p = 0.02) and a shorter median postoperative stay (6 vs. 7 days, p = 0.03) during stoma closure operation than that of the TM group. In the TM group, obese cases showed a higher operative time of stoma closure operation (115.0 vs. 95.0, p < 0.001), a higher parastomal hernia rate (p = 0.04), a higher peristomal adhesion extent (p = 0.005) and a longer postoperative stay of stoma closure operation (p = 0.02) compared with the non-obese cases, while in the OM group, no significant differences were observed between the obese and non-obese cases in terms of the above-mentioned factors. CONCLUSIONS: The OM exhibited more advantages than TM, notably in BMI obesity patients.

One-stitch versus traditional method of protective loop ileostomy in laparoscopic low anterior rectal resection: A retrospective comparative study.

BACKGROUND: Protective loop ileostomy is widely performed during rectal resection surgery. The study aimed to introduce the one-stitch method (OM) of protective loop ileostomy in laparoscopic low anterior resection and compare this new method with the traditional method (TM). MATERIALS AND METHODS: A retrospective analysis was conducted on 109 patients with pathologically diagnosed adenocarcinoma of the rectum from January 2017 to December 2018 in the study centre, and the intraoperative details and postoperative outcomes of the two groups were measured. RESULTS: A total of 95 patients were included: 54 underwent protective loop ileostomy with the TM, while 41 underwent surgery utilizing the OM. Univariate analysis demonstrated that the operative times of resection and closure were significantly shorter (resection, 200.0 vs. 227.5 min, P = 0.028; closure, 70.0 vs. 92.5 min, P = 0.018) and the peristomal adhesions during closure were milder (P = 0.007) in the OM group than in the TM group. The postoperative complications were similar in both groups. In multivariate analysis, the OM (OR 0.352, 95% CI = 0.155-0.799, P = 0.013) was a significant factor influencing the operative time of resection. The peristomal adhesion extent was the only independent risk factor for the stoma closure time (mild, OR 0.036, 95% CI = 0.010-0.129, P < 0.001; moderate, OR 0.128, 95% CI = 0.033-0.494, P = 0.003). No significant predictive factor of peristomal adhesion extent was identified in multivariable analysis. CONCLUSION: The OM of protective loop ileostomy in laparoscopic low anterior resection was time-saving, simple and easy to popularize and did not lead to more postoperative complications than the TM.

Genetic Fine Mapping and Genomic Annotation Defines Causal Mechanisms at A Novel Colorectal Cancer Susceptibility Locus in Han Chinese.

Genome-wide association studies of colorectal cancer (CRC) have identified two risk SNPs. The characterization of these risk regions in diverse racial groups with different linkage disequilibrium structure would aid in localizing the causal variants. Herein, fine mapping of the established CRC loci was carried out in 1,508 cases and 1,482 controls obtained from the Han Chinese population. One distinct association signal was identified at these loci, where fine mapping implicated rs1010208 as a functional locus. Next, the candidate target genes of functional SNP rs1010208 were analyzed using data from TCGA databases by expression quantitative trait loci analysis method; the data from Peking University People's Hospital were utilized for verification. The dual-luciferase reporter system analysis confirmed that rs1010208 is a regulatory region that can be mutated to decrease the expression of HINT1, resulting in proliferation and invasiveness of CRC.

Long non-coding RNA GAS5 inhibits cell proliferation, induces G0/G1 arrest and apoptosis, and functions as a prognostic marker in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide and its treatment remains a challenge. Effective control of cell survival and proliferation is critical in the prevention of oncogenesis and successful treatment of cancer. Long non-coding RNAs (lncRNAs) have emerged as primary regulators of carcinogenesis. Growth arrest specific 5 (GAS5), a lncRNA, is known to be aberrantly expressed in several types of cancer, however, the role of GAS5 in CRC remains unclear. In the present study, GAS5 mRNA expression was measured in CRC and adjacent normal mucosa tissue samples from 53 patients using reverse transcription-quantitative polymerase chain reaction analysis, in addition to seven CRC cell lines. GAS5 mRNA expression was observed to be markedly downregulated in human CRC tissues and cell lines. Decreased GAS5 expression was associated with an increase in tumor diameter [odds ratio (OR), 0.176 (95% CI, 0.053-0.586); P=0.003] and later tumor-node-metastasis stage [OR, 0.261 (95% CI, 0.083-0.819); P=0.019]. Patients with decreased GAS5 expression exhibited decreased overall survival rates compared with patients with increased GAS5 expression (P=0.015). The Cox proportional hazards model demonstrated that downregulated GAS5 expression was an independent prognostic factor for CRC (hazard ratio, 0.236; 95% confidence interval, 0.067-0.827; P=0.024). Functional assays demonstrated that overexpression of GAS5 inhibited cell proliferation and survival, and induced G0/G1 cell cycle arrest and apoptosis; however, knockdown of GAS5 expression enhanced cell proliferation, and reduced G0/G1 arrest and apoptosis. In conclusion, the results of the present study suggest that GAS5 is essential in the control of apoptosis and cell growth in CRC. Therefore, GAS5 may represent a novel prognostic and diagnostic marker of CRC, in addition to being a potential therapeutic target.

Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling.

The progression of distant metastasis cascade is a multistep and complicated process, frequently leading to a poor prognosis in cancer patients. Recently, growing evidence has indicated that deregulation of microRNAs (miRNAs) contributes to tumorigenesis and tumor progression in colorectal cancer (CRC). In the present study, by comparing the miRNA expression profiles of CRC tissues and corresponding hepatic metastasis tissues, we established the downregulation of miR-199b in CRC metastasis tissues. The decrease in miR-199b expression was significantly correlated to late TNM stage and distant metastasis. Moreover, Kaplan-Meier curves showed that CRC patients with high expression level of miR-199b had a longer median survival. Functional assays results indicated that the restoration of miR-199b considerably reduced cell invasion and migration in vitro and in vivo, and increased the sensitivity to 5-FU and oxaliplatin. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-199b in CRC. The expression of miR-199b was inversely correlated with SIRT1 in CRC specimens. SIRT1 knockdown produced effects on biological behavior that were similar to those of miR-199b overexpression. Furthermore, through Human Tumor Metastasis PCR Array we discovered KISS1 was one of the downstream targets of SIRT1. Silencing of SIRT1 upregulated KISS1 expression by enhancing the acetylation of the transcription factor CREB. The latter was further activated via binding to the promoter of KISS1 to induce transcription. Thus, we concluded that miR-199b regulates SIRT1/CREB/KISS1 signaling pathway and might serve as a prognosis marker or a novel therapeutic target for patients with CRC.

Low versus high radioiodine activity to ablate the thyroid after thyroidectomy for cancer: a meta-analysis of randomized controlled trials.

It is not known whether low-dose radioiodine is as effective as high-dose radioiodine for treating patients with differentiated thyroid cancer after surgery. This study compared ablation success rates of different doses of radioiodine in patients with differentiated thyroid cancer after thyroidectomy. Fifteen randomized controlled trials were obtained from PubMed, Embase, and Cochrane Library (1966 to February 2013). Stata version 12.0 was used to pool the outcomes. Mantel-Haenszel (MH) and inverse variance (IV) methods were used in a fixed-effects and random-effects model, respectively. The relative risk (RR) with 95% confidence interval (CI) was used to compare the success rates of different doses of radioiodine. There were a total of 3,046 patients. The pooled RR for comparing ablation success with low- and high-dose radioiodine was 0.90 (95% CI 0.83-0.98, IV). Excluding a study with a distinctive outcome, sensitivity analysis showed that the pooled RR was 0.95 (95% CI 0.92-0.99, MH). In subgroup analysis, the pooled RR of three studies that only administrated radioiodine to patients with pT2-4 cancer was 0.93 (95% CI 0.83-1.04, MH); the pooled RR of five studies with total thyroidectomy for all patients was 0.96 (95% CI 0.92-1.00, MH); and the pooled RR of four studies that used thyrotropin α to stimulate serum thyrotropin was 0.96 (95% CI 0.90-1.02, MH). The pooled RRs for comparing ablation success for moderate-dose versus high-dose and low-dose radioiodine were 0.94 (95% CI 0.85-1.04, IV) and 0.87 (95% CI 0.73-1.04, IV), respectively. Low-dose radioiodine can be used in patients undergoing total thyroidectomy. For those who receive insufficient surgical treatment, high-dose radioiodine is more appropriate.

Use of genome-wide association studies for cancer research and drug repositioning.

Although genome-wide association studies have identified many risk loci associated with colorectal cancer, the molecular basis of these associations are still unclear. We aimed to infer biological insights and highlight candidate genes of interest within GWAS risk loci. We used an in silico pipeline based on functional annotation, quantitative trait loci mapping of cis-acting gene, PubMed text-mining, protein-protein interaction studies, genetic overlaps with cancer somatic mutations and knockout mouse phenotypes, and functional enrichment analysis to prioritize the candidate genes at the colorectal cancer risk loci. Based on these analyses, we observed that these genes were the targets of approved therapies for colorectal cancer, and suggested that drugs approved for other indications may be repurposed for the treatment of colorectal cancer. This study highlights the use of publicly available data as a cost effective solution to derive biological insights, and provides an empirical evidence that the molecular basis of colorectal cancer can provide important leads for the discovery of new drugs.

MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway.

Tumor growth cascade is a complicated and multistep process with numerous obstacles. Until recently, evidences have shown the involvement of microRNAs (miRNAs) in tumorigenesis and tumor progression of various cancers, including colorectal cancer (CRC). In this study, we explored the role of miR-194 and its downstream pathway in CRC. We acquired data through miRNA microarray profiles, showing that the expression of miR-194 was significantly suppressed in CRC tissues compared with corresponding noncancerous tissues. Decreased miR-194 expression was obviously associated with tumor size and tumor differentiation, as well as TNM stage. Both Kaplan-Meier and multivariate survival analysis showed that downregulated miR-194 was associated with overall survival. Moreover, functional assays indicated that overexpression of miR-194 in CRC cell lines inhibited cell proliferation both in vitro and in vivo. In addition, using dual-luciferase reporter gene assay, we found MAP4K4 was the direct target of miR-194. Silencing of MAP4K4 resulted in similar biological behavior changes to that of overexpression of miR-194. We also observed through Human Gene Expression Array that MDM2 was one of the downstream targets of MAP4K4. Knockdown of MAP4K4 downregulated MDM2 expression through transcription factor c-Jun binding to the -1063 to -1057 bp of the promoter. These results suggest that miR-194, regulating the MAP4K4/c-Jun/MDM2 signaling pathway, might act as a tumor suppressor and serve as a novel target for CRC prevention and therapy.