The potential of ferrihydrite-synthetic humic-like acid composite as a soil amendment for metal-contaminated agricultural soil: Immobilization mechanisms by combining abiotic and biotic perspectives.

In-situ passivation technique has attracted increasing attention for metal-contaminated agricultural soil remediation. However, metal immobilization mechanisms are mostly illustrated based on metal speciation changes and alterations in soil physicochemical properties from a macroscopic and abiotic perspective. In this study, a ferrihydrite-synthetic humic-like acid composite (FH-SHLA) was fabricated and applied as a passivator for a 90-day soil incubation. The heavy metals immobilization mechanisms of FH-SHLA were investigated by combining both abiotic and biotic perspectives. Effects of FH-SHLA application on soil micro-ecology were also evaluated. The results showed that the 5%FH-SHLA treatment significantly decreased the DTPA-extractable Pb, Cd and Zn by 80.75%, 46.82% and 63.63% after 90 days of incubation (P < 0.05), respectively. Besides, 5% FH-SHLA addition significantly increased soil pH, soil organic matter content and cation exchange capacity (P < 0.05). The SEM, FTIR, and XPS characterizations revealed that the abiotic metal immobilization mechanisms by FH-SHLA included surface complexation, precipitation, electrostatic attraction, and cation-π interactions. For biotic perspective, in-situ microorganisms synergistically participated in the immobilization process via sulfide precipitation and Fe mineral production. FH-SHLA significantly altered the diversity and composition of the soil microbial community, and enhanced the intensity and complexity of the microbial co-occurrence network. Both metal bioavailability and soil physiochemical parameters played a vital role in shaping microbial communities, while the former contributed more. Overall, this study provides new insight into the heavy metal passivation mechanism and demonstrates that FH-SHLA is a promising and environmentally friendly amendment for metal-contaminated soil remediation.

Immunotherapy of microsatellite stable colorectal cancer: resistance mechanisms and treatment strategies.

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.

Targeting key RNA methylation enzymes to improve the outcome of colorectal cancer chemotherapy (Review).

RNA methylation modifications are closely linked to tumor development, migration, invasion and responses to various therapies. Recent studies have shown notable advancements regarding the roles of RNA methylation in tumor immunotherapy, the tumor microenvironment and metabolic reprogramming. However, research on the association between tumor chemoresistance and N6­methyladenosine (m6A) methyltransferases in specific cancer types is still scarce. Colorectal cancer (CRC) is among the most common gastrointestinal cancers worldwide. Conventional chemotherapy remains the predominant treatment modality for CRC and chemotherapy resistance is the primary cause of treatment failure. The expression levels of m6A methyltransferases, including methyltransferase­like 3 (METTL3), METTL14 and METTL16, in CRC tissue samples are associated with patients' clinical outcomes and chemotherapy efficacy. Natural pharmaceutical ingredients, such as quercetin, have the potential to act as METTL3 inhibitors to combat chemotherapy resistance in patients with CRC. The present review discussed the various roles of different types of key RNA methylation enzymes in the development of CRC, focusing on the mechanisms associated with chemotherapy resistance. The progress in the development of certain inhibitors is also listed. The potential of using natural remedies to develop antitumor medications that target m6A methylation is also outlined.

[Corrigendum] METTL3 antagonizes 5­FU chemotherapy and confers drug resistance in colorectal carcinoma.

Subsequently to the publication of the above article, the authors alerted us to the fact that the data shown in Fig. 8I (for the 'Sh­CN / 0' panel) on p. 11 were mistakenly selected from those data belonging to the experiments shown in Fig. 7H (the 'Sh­CN / 0' panel) of this paper during the final assembly of the figures for review. Note that this error did not affect the conclusions reported in this paper, as both Fig. 7H ('Sh­CN / 0') and Fig. 8I ('Sh­CN / 0') show negative controls of the Comet assay, with no obvious trailing. The revised version of Fig. 8, showing the correct data for the 'Sh­CN / 0' panel in Fig. 8I, is shown on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 61: 106, 2022; DOI: 10.3892/ijo.2022.5396].

A Randomized Phase III Study of Anlotinib Versus Bevacizumab in Combination With CAPEOX as First-Line Therapy for RAS/BRAF Wild-Type Metastatic Colorectal Cancer: A Clinical Trial Protocol.

Background: Chemotherapy combined with antivascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor monoclonal antibodies is the most promising approach to prolong survival and improve the quality of life of patients with unresectable metastatic colorectal cancer (mCRC). Anlotinib is an oral antiangiogenic tyrosine kinase inhibitor that targets VEGF receptors 1/2/3, fibroblast growth factor receptors 1-4, and platelet-derived growth factor receptors a/ß. Since anlotinib combined with oxaliplatin and capecitabine (CAPEOX) as a first-line treatment was previously shown to be effective and safe for patients with RAS/BRAF wild-type (WT) mCRC, we designed this randomized, open-label, parallel-group, non-inferiority, phase III study to evaluate the efficacy and safety of anlotinib plus CAPEOX versus bevacizumab plus CAPEOX in patients with RAS/BRAF WT mCRC. Methods/design: The primary inclusion criteria are Eastern Cooperative Oncology Group performance status 0/1, confirmed RAS/BRAF WT colorectal adenocarcinoma, and unresectable metastases assessed by a multidisciplinary team. The main exclusion criteria are as follows: high microsatellite instability or deficient mismatch repair status, resectable or potentially resectable metastases, and previous systemic therapy for mCRC. A total of 698 patients will be randomized into the anlotinib and bevacizumab groups in a 1:1 ratio. Patients will receive 4 to 8 cycles of induction therapy (CAPEOX plus anlotinib or bevacizumab), followed by maintenance treatment (capecitabine plus anlotinib or bevacizumab) until disease progression or unacceptable toxicity. Progression-free survival (PFS) assessed by an independent review committee is the primary endpoint, whereas investigator-assessed PFS, overall survival, objective response rate, disease control rate, duration of response, resection rate of liver metastases, quality of life, and safety are the secondary endpoints. Enrollment commenced in May 2021. Discussion: A prospective, randomized, phase III trial will provide a meaningful comparison of the efficacy and safety of anlotinib plus CAPEOX with standard treatment for patients with unresectable RAS/BRAF WT mCRC.

Adenocarcinoma arising in an ectopic enterogenous cyst: A rare case report and review of literature.

Enterogenous cyst (EC) is a rare congenital lesion generally located in the central nervous system, such as in the cerebral hemispheres, posterior fossa, or spinal canal. They are usually benign lesions, and malignant transformation is rare. A 42-year-old woman felt an obvious pain in the lump and went to a local hospital for local lumpectomy. After 7 months, she again felt pain in the buttocks and difficulty in urinating and defecation. The computed tomography (CT) scan showed a mass in the pelvis. Sacrococcygeal cyst excision was performed 10 days later, and postoperative pathology showed epidermoid cyst. Shortly after, the patient recovered and was discharged from the hospital; the pain in the buttocks continued to recur. Puncture and drainage were performed five times. Later, the patient went to our hospital for treatment, and pelvic MRI showed multiple abnormal signal shadows in the presacral and sacrococcygeal regions, some of which were considered abscesses, and some were cystic lesions. She underwent tumor resection and was diagnosed with EC with locally moderately differentiated adenocarcinoma. Four months later, the patient's symptoms of swelling and pain recurred. MRI examination showed multiple high-signal T2 shadows in the anterior sacral and subcutaneous tissues of the buttocks, and enhanced scan showed partial marginal enhancement. After assessment, the patient was given a radiation dose of 60 Gy/25F. ECs in the anterior sacral and soft tissue of the buttocks are very rare, and the case of carcinomatous transformation has never been reported. Therefore, we discussed the clinicopathological features of ectopic ECs and reviewed the literature.

METTL3 antagonizes 5­FU chemotherapy and confers drug resistance in colorectal carcinoma.

Colorectal cancer (CRC) is one of top five leading causes of cancer­associated mortalities worldwide. 5­Fluorouracil (5­FU) is the first­line chemotherapeutic drug in the treatment of CRC; however, its antineoplastic efficiency is limited due to acquired drug resistance. The regulatory mechanism underlying 5­FU chemotherapeutic response and drug resistance in CRC remains largely unknown. The present study identified that silencing of methyltransferase­like 3 (METTL3) suppressed the proliferation and migration of CRC HCT­8 cells. Using cell survival assays, flow cytometric and colony formation analyses, it was revealed that inhibition of METTL3 sensitized HCT­8 cells to 5­FU by enhancing DNA damage and inducing apoptosis in HCT­8 cells under 5­FU treatment. Furthermore, the expression of METTL3 was upregulated in 5­FU­resistant CRC cells (HCT­8R), which contributed to drug resistance through regulation of RAD51 associated Protein 1 (RAD51AP1) expression. Western blotting, immunofluorescence staining and drug sensitivity assays demonstrated that knockdown of METTL3 augmented 5­FU­induced DNA damage and overcame 5­FU­resistance in HCT­8R cells, which could be mimicked by inhibition of RAD51AP1. The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5­FU resistance in CRC, and targeting METTL3/RAD51AP1 may be a promising adjuvant therapeutic strategy for patients with CRC, particularly for those with 5­FU­resistant CRC.

Hsa_circ_0060927 participates in the regulation of Caudatin on colorectal cancer malignant progression by sponging miR-421/miR-195-5p.

BACKGROUND: Caudatin is extracted from radix cynanchi bungei and has an inhibitory effect on cancer progression. The study aims to reveal the impacts of hsa_circ_0060927 on Caudatin-mediated colorectal cancer (CRC) development and the underneath mechanism. METHODS: The expression levels of hsa_circ_0060927, microRNA-421 (miR-421) and miR-195-5p were detected by quantitative real-time reverse transcription-polymerase chain reaction. The protein expression was analyzed by Western blot or immunohistochemistry assay. Cell viability and proliferation were analyzed by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide or 5-Ethynyl-29-deoxyuridine assay. Cell apoptosis was quantified by flow cytometry analysis. Cell migration and invasion were investigated by transwell assay. The putative associations among hsa_circ_0060927, miR-421 and miR-195-5p were predicted by the starbase online database, and identified by dual-luciferase reporter, RNA pull-down and RNA immunoprecipitation (RIP) assays. The impacts of Caudatin treatment on tumor growth in vivo were revealed by a xenograft tumor model assay. RESULTS: Hsa_circ_0060927 expression was significantly upregulated, whereas miR-421 and miR-195-5p were downregulated in CRC tissues and cells compared with control groups. Hsa_circ_0060927 expression was closely associated with lymph node metastasis and tumor-node-metastasis stage. Caudatin treatment significantly decreased hsa_circ_0060927 expression but increased miR-421 and miR-195-5p expression. Caudatin exposure suppressed CRC cell proliferation, migration and invasion, and induced cell apoptosis; however, hsa_circ_0060927 overexpression hindered these impacts. Additionally, hsa_circ_0060927 was associated with miR-421/miR-195-5p. Depletion of miR-421 or miR-195-5p attenuated the influences of hsa_circ_0060927 silencing on CRC development. Furthermore, Caudatin treatment repressed tumor growth in vivo. CONCLUSION: Caudatin inhibited CRC cell malignancy through the hsa_circ_0060927/miR-421/miR-195-5p pathway, which provided a potential therapeutic agent for CRC.

The Research Progress of Direct KRAS G12C Mutation Inhibitors.

KRAS mutations have long been considered undruggable. However, a series of direct KRAS mutation inhibitors have been developed since the switch II pocket was discovered recently. This review will summarize progress in the development of direct KRAS G12C mutation inhibitors, current relevant drugs under study and challenges that need to be considered in future research.

Corrigendum: The Research Progress of Direct KRAS G12C Mutation Inhibitors.

[This corrects the article DOI: 10.3389/pore.2021.631095.].

Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats.

BACKGROUND: Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC. AIM: To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis. METHODS: DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG. RESULTS: At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively. CONCLUSION: EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.

CASC21, a FOXP1 induced long non-coding RNA, promotes colorectal cancer growth by regulating CDK6.

Emerging studies indicate that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). Here, we reported lncRNA CASC21, which is induced by FOXP1, functions as an oncogene in CRC. We systematically elucidated its clinical significance and possible molecular mechanism in CRC. LncRNA expression in CRC was analyzed by RNA-sequencing data in TCGA. The expression level of CASC21 in tissues was determined by qRT-PCR. The functions of CASC21 was investigated by in vitro and in vivo assays (CCK8 assay, colony formation assay, EdU assay, xenograft model, flow cytometry assay, immunohistochemistry (IHC) and Western blot). Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP) and luciferase reporter assays were utilized to demonstrate the potential mechanisms of CASC21. CASC21 is overexpressed in CRC and high CASC21 expression is associated with poor survival. Functional experiments revealed that CASC21 promotes CRC cell growth. Mechanistically, we found that CASC21 expressed predominantly in the cytoplasm. CASC21 could interact with miR-539-5p and regulate its target CDK6. Together, our study elucidated that CASC21 acted as an oncogene in CRC, which might serve as a novel target for CRC diagnosis and therapy.

Clinical significance of MLH1/MSH2 for stage II/III sporadic colorectal cancer.

BACKGROUND: The development of colorectal cancer (CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes. In the process of DNA replication, base mismatch often occurs due to various factors leading to abnormal expression of mismatch repair genes (MMR), among which MLH1 and MSH2 are the most important. Recently, numerous studies indicated that MLH1/MSH2 phenotype is associated with CRC. We wanted to elucidate the role of MLH1/MSH2 in the prediction and prognosis of CRC through long-term clinical observation. AIM: To evaluate the prognostic and predictive significance of MLH1/MSH2 in patients with stage II-III CRC using immunohistochemical analysis and GeneScan. METHODS: Specimens from 681 patients with CRC (395 stage II and 286 stage III, 387 males and 294 females) who underwent curative surgical resection from 2013 to 2016 were tested. Immunohistochemistry was used to analyze MMR status and the microsatellite status of 133 patients was determined by GeneScan analysis. RESULTS: Five hundred and fifty (80.76%) patients were MLH1/MSH2 positive and 131 (19.24%) were negative by immunohistochemistry. MLH1/MSH2-positive tumors were significantly more frequent in the colon than in the rectum, and had poor differentiation and less mucin production (P < 0.05). Patients of different groups did not differ in terms of age, gender, tumor size, tumor stage, lymphocytic infiltration, or circumscribed margin. MLH1/MSH2-negative patients had a more favorable OS than MLH1/MSH2-positive patients (P < 0.001). Univariate and multivariate analyses demonstrated MLH1/MSH2 expression as an independent prognostic and predictive factor for stage II/III CRC. MLH1/MSH2 expression was a strong prognostic factor in all patients [P < 0.001, hazard ratio (HR) = 4.064, 95%CI: 2.241-7.369]. Adjuvant chemotherapy had a greater correlation with survival advantage in MLH1/MSH2-negative patients with stage III disease (P < 0.001, HR = 7.660, 95%CI: 2.974-15.883). However, patients with stage II disease or MLH1/MSH2-positive patients with stage III disease did not benefit from adjuvant chemotherapy. GeneScan analysis demonstrated that among 133 patients, 105 (78.95%) were microsatellite stable, and 28 (21.05%) had microsatellite instability (MSI), including 18 (13.53%) with high MSI and 10 (7.52%) with low MSI. This is consistent with the immunohistochemical results. CONCLUSION: MLH1/MSH2 phenotype constitutes a pathologically and clinically distinct subtype of sporadic CRC. MLH1/MSH2 is an independent prognostic and predictive factor for outcome of stage II-III CRC.

Fast Response Solar-Blind Photodetector with a Quasi-Zener Tunneling Effect Based on Amorphous In-Doped Ga2O3 Thin Films.

A high-performance solar-blind photodetector with a metal-semiconductor-metal structure was fabricated based on amorphous In-doped Ga2O3 thin films prepared at room temperature by radio frequency magnetron sputtering. The photodetector shows a high responsivity (18.06 A/W) at 235 nm with a fast rise time (4.9 µs) and a rapid decay time (230 µs). The detection range was broadened compared with an individual Ga2O3 photodetector because of In doping. In addition, the uneven In distribution at different areas in the film results in different resistances, which causes a quasi-Zener tunneling internal gain mechanism. The quasi-Zener tunneling internal gain mechanism has a positive impact on the fast response speed and high responsivity.

A meta-analysis of caspase-8 -652 6N del polymorphism and digestive tract cancer risk.

Caspase-8 (CASP8) is one key regulator of apoptosis of T lymphocytes and is encoded by the CASP8 gene. It has been reported that the six-nucleotide deletion polymorphism (-652 6N del) of the CASP8 gene had effect on some cancer risk. Few studies explored the association between CASP8 gene polymorphism and digestive tract cancer risk. To evaluate the association between the CASP8 -652 6N del polymorphism and the risk of digestive tract cancer, we conducted this meta-analysis. We found that CASP8-652 6N del polymorphism was associated with a significantly reduced risk of digestive tract cancer in the co-dominant model (del/del vs. ins/ins: OR= 0.82, 95%CI= 0.72-0.95; del/ins vs. ins/ins: OR= 0.92, 95%CI= 0.87-0.97; dominant model (del/ins+ del/del vs. ins/ins: OR= 0.91, 95%CI= 0.87-0.96, recessive model: del/del vs. del/ins+ ins/ins: OR= 0.85, 95%CI= 0.75-0.97). In the stratified analysis by cancer types, we found that all genetic models had protective effect on gastric cancer. Similar results were observed for colorectal cancer under heterozygote comparison and dominant model, but not under homozygote comparison or recessive model. In addition, a significantly decreased risk was found on esophageal cancer for most genetic models, except heterozygote comparison. When stratified by ethnicity and source of control, an evidently decreased risk was identified in the Asian populations and population-based studies. In conclusion, there exists an association between the CASP8 -652 6N del polymorphism and reduced digestive cancer risk, especially among Asians and population-based studies.

miR­1273g­3p promotes proliferation, migration and invasion of LoVo cells via cannabinoid receptor 1 through activation of ERBB4/PIK3R3/mTOR/S6K2 signaling pathway.

MicroRNAs (miR) are important in various crucial cell processes including proliferation, migration and invasion. Dysregulation of miRNAs have been increasingly reported to contribute to colorectal cancer. However, the detailed biological function and potential mechanisms of miR­1273g­3p in colorectal cancer remain poorly understood. The expression levels of miR­1273g­3p in human colorectal cancer LoVo cell lines were detected via reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The target genes of miR­1273g­3p were predicted by bioinformatics and verified by a luciferase reporter assay, RT­qPCR and western blotting. The MTT, wound­healing and Transwell assays were used to examine the biological functions of miR­1273g­3p in LoVo cells. The potential molecular mechanisms of miR­1273g­3p on LoVo cell proliferation, migration and invasion was detected by western blotting. The results of the present study demonstrated that miR­1273g­3p expression was extensively upregulated in LoVo cells compared with the normal colon epithelial NCM460 cell line. Further studies indicated that miR­1273g­3p inhibitor significantly suppressed LoVo cell proliferation, migration and invasion compared with inhibitor control. Following this, the cannabinoid receptor 1 (CNR1) was identified as a direct target gene of miR­1273g­3p. Knockdown of CNR1 restored the phenotypes of LoVo cells transfected with miR­1273g­3p inhibitor. Furthermore, the potential molecular mechanism of miR­1273g­3p on LoVo cell proliferation, migration and invasion may be mediated by activating the Erb­B2 receptor tyrosine kinase 4 (ERBB4)/phosphoinositide­3­kinase regulatory subunit 3 (PIK3R3)/mechanistic target of rapamycin (mTOR)/S6 kinase 2 (S6K2) signaling pathway. These observations indicated that miR­1273g­3p promoted the proliferation, migration and invasion of LoVo cells via CNR1, and this may have occurred through activation of the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway, suggesting that miR­1273g­3p may serve as a novel therapeutic target for the effective treatment of colorectal cancer.

Prognostic significance of microRNA-16 expression in human colorectal cancer.

BACKGROUND: MicroRNAs (miRNAs), small noncoding RNAs, have been reported to be highly involved in the formation and progression of all types of human cancer including colorectal cancer (CRC). Therefore, miRNAs are also potential prognostic biomarkers in CRC patients. The aim of this study was to detect the expression of miR-16 in human CRC tissues and investigate its clinicopathologic or prognostic significance. METHODS: TaqMan quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was performed to determine the expression of miR-16 in 143 primary CRC tissues and 18 corresponding normal colonic mucosa from patients who had undergone surgery. The association of miR-16 expression with clinicopathologic features of CRC patients was statistically analyzed. Kaplan-Meier analyses were used to assess patient survival. Univariate and multivariate Cox analyses were performed. RESULTS: The relative level of miR-16 in 18 CRC tissues was significantly lower than that in corresponding normal colonic mucosa (p < 0.001). Statistical analyses revealed that the status of miR-16 expression was closely associated with tumor differentiation, lymph node metastasis, L category, V category, TNM stage, and tumor recurrence of CRC (p = 0.001, 0.003, 0.001, 0.005, 0.003, and 0.017, respectively). Kaplan-Meier analyses indicated that patients with low-miR-16 had lower 5-year overall survival than those with high-miR-16 (31.2 vs. 58.3 %; p = 0.0012). Multivariate Cox regression analyses indicated that the status of miR-16 expression might be an independent prognostic factor for CRC patients (hazard ratio 1.67; 95 % confidence interval 1.22-2.54; p = 0.018). CONCLUSIONS: Down-regulation of miR-16 plays critical roles in CRC progression. Low miR-16 expression is an independent factor predicting a poor prognosis for CRC patients.