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Postoperative complications related to anastomosis, including postoperative anastomotic bleeding and anastomotic leakage, remain a serious issue. The effect of anastomotic devices on suture complications during intestinal anastomosis remains unclear. The present study examined the utility of automated anastomotic devices for reducing anastomotic complication risks. A retrospective cohort study of colorectal cancer surgeries in which an anastomosis device was used at Osaka University Hospital (Suita, Japan) between January 2018 and December 2022 was conducted. Cases of emergency surgery, inflammatory bowel disease and simultaneous surgery for other cancers were excluded. Experienced gastrointestinal surgeons performed manual anastomosis using the ETHICON Circular Stapler CDH or EEA Circular Stapler, and automatic anastomosis using the ECHELON CIRCULAR Powered Stapler, with no observed operator bias. Additionally, a meta-analysis that included other study results was performed. The outcomes included postoperative complications, mainly anastomotic leakage. The study included 414 patients: 231 in the manual circular stapler group and 183 in the powered circular stapler (PCS) group. Although this retrospective study found no statistically significant association between the anastomotic device used and anastomotic complications, an increased risk ratio was observed in the manual group compared with the automatic group when restricted to elderly patients. Similarly, a meta-analysis found a significantly higher anastomotic complication risk in the manual group compared with the automatic group (random-effects model; odds ratio, 0.376; 95% confidence interval, 0.232-0.610; P<0.0001). The findings of the present study suggested that a PCS is useful for reducing the anastomotic complication risk in patients undergoing colorectal cancer surgery. [ABSTRACT FROM AUTHOR]

Postoperative complications related to anastomosis, including postoperative anastomotic bleeding and anastomotic leakage, remain a serious issue. The effect of anastomotic devices on suture complications during intestinal anastomosis remains unclear. The present study examined the utility of automated anastomotic devices for reducing anastomotic complication risks. A retrospective cohort study of colorectal cancer surgeries in which an anastomosis device was used at Osaka University Hospital (Suita, Japan) between January 2018 and December 2022 was conducted. Cases of emergency surgery, inflammatory bowel disease and simultaneous surgery for other cancers were excluded. Experienced gastrointestinal surgeons performed manual anastomosis using the ETHICON Circular Stapler CDH or EEA Circular Stapler, and automatic anastomosis using the ECHELON CIRCULAR Powered Stapler, with no observed operator bias. Additionally, a meta-analysis that included other study results was performed. The outcomes included postoperative complications, mainly anastomotic leakage. The study included 414 patients: 183 in the manual circular stapler group and 231 in the powered circular stapler (PCS) group. Although this retrospective study found no statistically significant association between the anastomotic device used and anastomotic complications, an increased risk ratio was observed in the manual group compared with the automatic group when restricted to elderly patients. Similarly, a meta-analysis found a significantly higher anastomotic complication risk in the manual group compared with the automatic group (random-effects model; odds ratio, 0.376; 95% confidence interval, 0.232-0.610; P<0.0001). The findings of the present study suggested that a PCS is useful for reducing the anastomotic complication risk in patients undergoing colorectal cancer surgery., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Mizumoto et al.)

Although accumulating evidence has confirmed the potential biological functions of long non-coding RNAs (lncRNAs) as competitive endogenous RNAs (ceRNAs) in colorectal tumorigenesis and progression, few studies have focused on rectosigmoid junction cancer. In the present study, a comprehensive analysis was conducted to explore lncRNA-mediated ceRNA implications and their potential value for prognosis. lncRNA, microRNA (miR/miRNA) and mRNA expression profiles were downloaded from The Cancer Genome Atlas database. Subsequently, a lncRNA-miRNA-mRNA regulatory network was constructed to evaluate the functions of these differentially expressed genes on overall survival (OS) for rectosigmoid junction cancer. As a result, a rectosigmoid junction cancer-specific ceRNA network was successfully constructed with 7 differentially expressed (DE)lncRNAs, 16 DEmiRNAs and 71 DEmRNAs. Among the network, one DElncRNA (small nucleolar RNA host gene 20) and three mRNAs (sodium- and chloride-dependent taurine transporter, fibroblast growth factor 13 and tubulin polyglutamylase TTLL7) were significantly associated with OS (P<0.05). Additionally, two lncRNAs (KCNQ1OT1 and MIR17HG) interacted with most of the DEmiRNAs. Notably, two top-ranked miRNAs (hsa-miR-374a-5p and hsa-miR-374b-5p) associated networks were identified to be markedly associated with the pathogenesis. Furthermore, four DEmRNAs (caveolin-1, MET, filamin-A and AKT3) were enriched in the Kyoto Encylopedia of Gene and Genomes pathway analysis, as well as being included in the ceRNA network. In summary, the present results revealed that a specific lncRNA-miRNA-mRNA network was associated with rectosigmoid junction cancer, providing several molecules that may be used as novel prognostic biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

The frequency of deficient mismatch repair (dMMR) or microsatellite instability-high colorectal cancer (CRC) is estimated to be ~15% of all patients with CRC; however, the patients reported are limited to surgical cases, and the frequency of patients exhibiting stage 0 disease is not considered, despite the currently increasing use of endoscopic techniques to cure a number of these patients. In the present study, the DNA MMR status for stage 0 patients with CRC treated using endoscopic submucosal dissection or endoscopic mucosal resection was analyzed via immunohistochemical staining of four types of proteins, namely MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6 and PMS1 homolog 2 MMR system component, in adenocarcinoma specimens. Notably, none of the endoscopically resected specimens exhibited dMMR among the 41 patients diagnosed with stage 0 CRC. Since tumors harboring dMMR progress more rapidly than tumors with chromosomal instability, the present results highlight the importance of tumor resection during very early phases that exist before the promoter region of MLH1 becomes hypermethylated, resulting in a loss of DNA MMR function. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the microarray data of human colorectal cancer (CRC) tissues and identify novel therapeutic targets for CRC. Microarray analysis from the GSE73360 and GSE84984 datasets was performed to identify novel long non-coding RNAs (lncRNAs) that were differentially expressed in human CRC tissues. Additionally, small interfering RNAs were used to deplete the expression of the indicated lncRNAs in cells. Colony-formation, wound-closure, and transwell assays were performed on CRC cells to assess their proliferation and migration capacities. Through microarray analysis, SCARNA9L, SLMO2-ATP5E and LOC100132062 were identified as differentially expressed lncRNAs in CRC tissues. The present study demonstrated that the ablation of SCARNA9L inhibited cell proliferation and arrested the cell cycle of SW480 and SW620 CRC cells. Additionally, depletion of SCARNA9L restrained the migration of CRC cells in vitro. Overall, the present study investigated the potential involvement of SCARNA9L in CRC and suggests SCARNA9L as a potential biomarker. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of numerous types of cancer, including colorectal cancer (CRC). Patients with CRC and deficient mismatch repair or high microsatellite instability could benefit from ICI treatment, although the response rate of most patients is low. Therefore, the immune subtyping of patients with CRC is required in order to determine the subtypes suitable for ICI treatment. The present study used a cohort of patients with CRC from The Cancer Genome Atlas (TCGA) to perform molecular subtyping, with results validated in three CRC cohorts from the Gene Expression Omnibus. Non-negative matrix factorization was used to achieve consensus molecular subtyping. The tumor immune dysfunction and exclusion algorithm was used to predict potential ICI therapy responses and gene set enrichment analysis was performed to define different pathways associated with the immune response. Two distinct subtypes of CRC were finally identified in TCGA cohorts, which were characterized as significantly different prognostic subtypes (low-risk and high-risk subtypes). Higher expression of programmed death-ligand 1, higher proportion of tumor-infiltrating lymphocytes and tumor mutation burden were significantly enriched in the low-risk subtype. Further pathway analysis revealed that the low-risk subtype was associated with immune response activation and signaling pathways involved in 'antigen processing and presentation'. Three independent CRC cohorts were used to validate the above findings. In summary, two clinical CRC subtypes were identified, which are characterized by significantly different survival outcomes and immune infiltration patterns. The findings of the present study suggest that ICI treatment may be more effective in the low-risk CRC subtype. [ABSTRACT FROM AUTHOR]

The aim of the present study was to use a competing risk model to analyze the prognostic value of mucinous adenocarcinoma (MAC) in patients with colorectal cancer (CRC). An additional aim was to construct nomograms for estimating the 3- and 5-year overall survival (OS) and cancer specific survival (CSS) rates of patients with primary CRC with MAC. The data were extracted from the Surveillance, Epidemiology, and End Results database, and a Multivariate Cox model and competing risk model were applied to assess the OS and CSS. Cox-based and competing risk-based nomograms were constructed and internally validated by discrimination and calibration, using the bootstrapping method with 1,000 times replicates. A total of 13,035 MAC and 61,958 non-mucinous adenocarcinoma (NMAC) CRC patients were enrolled in the present study. Compared with NMAC, MAC patients had a poorer OS and CSS time in the overall population, and in subgroups that comprised metastatic, non-metastatic, male, site of sigmoid colon, rectosigmoid junction and rectal CRC cases (HR>1; P<0.05). The Cox and competing risk-based nomograms showed effective discrimination and calibration. In conclusion, MAC was associated with poor OS and CSS in patients with CRC of the distal colon and rectum. The nomograms of primary CRC patients with MAC may aid the identification of individual patients with a high risk of overall mortality and cancer-associated mortality within 3 or 5 years. [ABSTRACT FROM AUTHOR]

Tumor metastasis and anticancer drug resistance are the major causes of mortality in patients with colorectal cancer (CRC). Due to the limitations of conventional biomarkers, it is urgent to identify novel and valid biomarkers to predict the progression and prognosis of CRC. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect MAGT1 expression in CRC clinical samples or cell lines. Bioinformatics analysis was used to investigate the association between MAGT1 alteration and clinicopathological features of patients with CRC. The present study revealed that the transcription levels of magnesium transporter 1 (MAGT1) were significantly increased in CRC tissues compared with matched adjacent normal tissues. Overexpression of MAGT1 was associated with advanced tumor stage, N and M classification. In addition, for patients who underwent chemotherapy, patients in the MAGT1-low expression group exhibited a longer overall survival (OS) time than patients in the high-expression group. Patients with CRC treated with chemotherapy had a longer OS time than those treated without chemotherapy in the MAGT1-low expression group but not in the MAGT1-high expression group. Furthermore, MAGT1 was a valid but not an independent prognostic factor for CRC. Therefore, the present study highlighted that MAGT1 may serve as a valid biomarker for predicting the development, progression and poor prognosis of CRC. [ABSTRACT FROM AUTHOR]

The secretions of cancer cells alter epigenetic regulation in cancer stromal cells. The present study investigated the methylation changes in white blood cells (WBCs) caused by the secretions of colorectal cancer (CRC) cells. Changes in the DNA methylation of peripheral blood mononuclear cells (PBMCs) from normal individuals co-cultured with CRC cells were estimated using a methylation microarray. These changes were then compared against the DNA methylation changes and mRNA levels observed in the WBCs of patients with CRC. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) and matrix metalloproteinase 9 (MMP9) were selected to assess the DNA methylation of the WBCs from CRC patients using real-time methylation-specific PCR. The majority of the genes analyzed presented high levels of mRNA in the WBCs of the patients with CRC and DNA methylation in the co-cultured PBMCs. Intragenic methylation revealed the strongest association (P=8.52×10−21). For validation, MMP9 and PLOD1 were selected and used to test WBCs from 32 patients with CRC and 57 normal controls. The intragenic MMP9 methylation was commonly found (P<0.0001) with high sensitivity (90.63%) and high specificity (96.49%), and a positive predictive value of 93.33% and a negative predictive value of 93.22%. PLOD1 methylation was revealed to have lower sensitivity (30.00%) but higher specificity (97.92%). In addition to circulating WBCs, MMP9 protein expression was observed in infiltrating WBCs and the metastatic lymph nodes of patients with CRC. In conclusion, CRC cells secrete factors that induce genome wide DNA methylation changes in the WBCs of patients with CRC. These changes, including intragenic MMP9 methylation in WBCs, are promising CRC biomarkers to be tested in future CRC screening studies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common types of gastrointestinal malignancy. Traditional therapeutic options for CRC exhibit a limited effect. Adoptive cellular therapy has emerged as a new treatment strategy for CRC. Dendritic cells (DCs) are potent antigen-presenting cells. Specific cytotoxic T lymphocytes (CTLs) activated by DCs pulsed with tumor lysate have been reported to be a safe and promising treatment approach for CRC. However, the antitumor effect of specific CTLs remains limited. The low immunogenicity of tumor-associated antigens (TAAs) is the main reason for this limited therapeutic effect. In the present study, α-gal epitopes were synthesized on the CRC cell line SW620 to increase the immunogenicity of TAAs. DCs were pulsed with α-gal-expressing tumor lysate and CTLs were activated by these DCs. The cytotoxicity of CTLs was measured in vitro. The results demonstrated that DCs pulsed with α-gal-expressing tumor lysate can increase the frequency of CD3+CD8+ CTLs and natural killer T cells, increase the level of tumor necrosis factor-α produced by CTLs and enhance the cytotoxicity of CTLs against tumor cells. Therefore, this novel approach may be an effective treatment strategy for patients with CRC. [ABSTRACT FROM AUTHOR]

An increasing number of studies have confirmed that miR-124 exhibits a suppressive role in glioblastoma, cervical cancer and breast cancer; however, the function of miR-124 in colorectal cancer (CRC) has not been completely elucidated. In the present study, miR-124 expression was confirmed by reverse transcription-quantitative PCR in 80 colorectal tissues and para-cancerous tissues. The influence of altered miR-124 expression was analyzed by statistical approaches including Cox multivariate regression analysis and the Kaplan-Meier method, and the target genes of miR-124 were confirmed by luciferase reporter assays. Immunohistochemical techniques were also performed in order to measure the expression levels of target proteins. miR-124 expression was observed to be decreased in colorectal tissue samples, and this phenomenon was correlated with adverse clinical indicators and poor patient survival time. Luciferase reporter assays indicated that miR-124 directly regulated TNF receptor associated factor 6 (TRAF6) 3′-untranslated region (UTR). Hence, it was proposed that miR-124 dysregulation may negatively influence the expression of TRAF6 and therefore serve as a biomarker of epithelial-mesenchymal transition in CRC tissues. In summary, the present study demonstrated that miR-124 regulates the expression of TRAF6, and may potentially function as an independent prognostic factor and therapeutic target in patients with CRC. [ABSTRACT FROM AUTHOR]

Long non‑coding RNA (Lnc)TCF7 is a novel lncRNA that is involved in tumorigenesis. Previous studies have revealed that lncTCF7 serves an essential role in maintaining cancer stem cell self‑renewal; however, the functions of lncTCF7 in colorectal cancer (CRC) remain unknown. Therefore, the present study aimed to investigate the role of lncTCF7 in CRC. LncTCF7 was upregulated in 52/58 CRC tissues, and its expression correlated with tumor size, lymph metastasis and tumor‑node‑metastasis stage in CRC. Knocking down lncTCF7 in colon cancer cell lines decreased cell proliferation, migration and invasion, while lncTCF7 overexpression showed opposite changes. In addition, lncTCF7 promoted cell proliferation in vivo. LncTCF7 activated the Wnt/β‑catenin signaling pathway, which is essential for cancer development. Survival analysis revealed that patients with higher expression of lncTCF7 had significantly worse prognosis compared with patients with low expression. These findings indicate that lncTCF7 regulates CRC progression and support the notion of lncTCF7 as a CRC prognostic marker. [ABSTRACT FROM AUTHOR]

It has been well recognized that the tumor microenvironment serves important roles in the progression and invasion of cancer. The desmoplastic reaction (DR) is a fibrous tissue reaction around tumor cells, and the prognostic significance of DR in colorectal cancer (CRC) has been established. Tumor deposits (TD) are also an important prognostic indicator of CRC. Notably, immature type DR has been linked to poor prognosis. In addition, immature type DR is significantly associated with a higher pT stage, presence of lymphovascular invasion and lymph node metastasis; however, to the best of our knowledge, the association between DR and TD has not yet been examined. The present study aimed to clarify this association. This study included 443 consecutive patients with pT3 or pT4 CRC who underwent surgical resection. The histopathological features, including DR and TD, were evaluated. Statistical analyses of the presence of TD, DR and other clinicopathological parameters were performed. The present cohort included 205 female and 238 male patients; 293 (66.1%) and 150 (33.9%) patients were classified as pT3 and pT4, respectively. Immature, intermediate and mature DR were noted in 282 (63.7%), 91 (20.5%) and 70 patients (15.8%), respectively. TD was observed in 93 (21.0%) patients. Immature type DR was significantly associated with a higher pT stage (P<0.0001), presence of lymph node metastasis (P<0.0001), lymphatic (P=0.0007), venous (P<0.0001) and perineural invasion (P<0.0001), and higher tumor budding (TB) (P<0.0001). Moreover, immature type DR was significantly associated with the presence of TD (P<0.0001). The present study demonstrated a significant association between immature type DR and the presence of TD, and suggested a close relationship between lymphovascular invasion, DR, TB and TD. Additional studies are required to analyze the detailed mechanism underlying the development of immature DR in CRC to define novel treatment strategies. [ABSTRACT FROM AUTHOR]

It has been well recognized that the tumor microenvironment serves important roles in the progression and invasion of cancer. The desmoplastic reaction (DR) is a fibrous tissue reaction around tumor cells, and the prognostic significance of DR in colorectal cancer (CRC) has been established. Tumor deposits (TD) are also an important prognostic indicator of CRC. Notably, immature type DR has been linked to poor prognosis. In addition, immature type DR is significantly associated with a higher pT stage, presence of lymphovascular invasion and lymph node metastasis; however, to the best of our knowledge, the association between DR and TD has not yet been examined. The present study aimed to clarify this association. This study included 443 consecutive patients with pT3 or pT4 CRC who underwent surgical resection. The histopathological features, including DR and TD, were evaluated. Statistical analyses of the presence of TD, DR and other clinicopathological parameters were performed. The present cohort included 205 female and 238 male patients; 293 (66.1%) and 150 (33.9%) patients were classified as pT3 and pT4, respectively. Immature, intermediate and mature DR were noted in 282 (63.7%), 91 (20.5%) and 70 patients (15.8%), respectively. TD was observed in 93 (21.0%) patients. Immature type DR was significantly associated with a higher pT stage (P<0.0001), presence of lymph node metastasis (P<0.0001), lymphatic (P=0.0007), venous (P<0.0001) and perineural invasion (P<0.0001), and higher tumor budding (TB) (P<0.0001). Moreover, immature type DR was significantly associated with the presence of TD (P<0.0001). The present study demonstrated a significant association between immature type DR and the presence of TD, and suggested a close relationship between lymphovascular invasion, DR, TB and TD. Additional studies are required to analyze the detailed mechanism underlying the development of immature DR in CRC to define novel treatment strategies., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Kobayashi et al.)

Colorectal cancer (CRC) is one of the most prevalent malignant diseases and metastasis is the leading cause of poor prognosis in patients with CRC. Further knowledge of the molecular mechanism underlying metastasis in CRC and the identification of new therapeutic targets are needed. Yes-associated protein (YAP) is a transcriptional regulator that is important in tumorigenesis and tumor cell proliferation. The present study investigated whether YAP was crucial for CRC migration and invasion. The protein expression levels were detected via western blotting, and migration and invasion were analyzed by Transwell migration and invasion assays. Subsequently, YAP expression was silenced using small interfering RNA. The mRNA expression levels were detected via reverse transcription-quantitative PCR and cell viability was assessed via Trypan blue exclusion assay. The results revealed that YAP protein levels were associated with migration and invasion of CRC cells. Notably, YAP small interfering RNA inhibited the migration and invasion of DLD-1 cells. In addition, the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway inhibitor LY294002 suppressed the migration and invasion of DLD-1 cells by decreasing the expression of YAP. Notably, the present study demonstrated that verteporfin mediated the suppression of migration and invasion of DLD-1 cells due to the decreased expression of YAP. Therefore, targeting YAP may be valuable for developing therapeutic strategies against CRC, and verteporfin may be an effective therapy to suppress the migration and invasion of CRC. [ABSTRACT FROM AUTHOR]

The incidence of colorectal cancer (CRC) has remained high in recent years, and 5-fluorouracil (5-FU) is a vital chemotherapeutic agent for its treatment. Our previous study reported that N-myc downstream-regulated gene 4 (NDRG4) plays a tumor-suppressive role in CRC, but the mechanisms associated with NDRG4 and 5-FU chemosensitivity remain unclear. The results of the present study demonstrate that NDRG4 sensitized CRC cells to 5-FU by upregulating DNA damage inducible transcript 3 (DDIT3). NDRG4 inhibited the proliferation of CRC cells and the activation of PI3K/AKT and ERK signaling. Furthermore, NDRG4 promoted CRC cell apoptosis induced by 5-FU. Mechanistic analyses revealed that NDRG4 upregulated DDIT3 expression, and that the proapoptotic effect of NDRG4 under 5-FU treatment conditions was dependent on DDIT3. These findings support the biological value of the association between NDRG4, DDIT3 and 5-FU chemosensitivity in CRC, and may advance the clinical treatment of CRC in the future. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. The aim of the present study was to investigate the expression of yes-associated protein (YAP) in CRC tissues, and to determine the relationship between the expression levels of YAP and the clinicopathological characteristics and prognosis of patients with CRC. Bioinformatics analysis was conducted to examine the expression of YAP and its correlation with clinicopathological characteristics and key genes, using functional enrichment analysis. Immunohistochemistry was used to detect YAP expression in 181 CRC tissue samples and 30 normal colorectal mucosa samples. Western blotting and reverse transcription-quantitative PCR were performed to detect the expression of YAP and β-catenin in CRC cells, and cellular proliferation was assessed using a Cell Counting Kit-8 assay. Finally, apoptosis was analyzed using flow cytometry. Immunohistochemical staining indicated that the positive expression rate of YAP in CRC tissues was 73.5%, which was significantly higher than that in normal colorectal mucosa samples. The expression of YAP in CRC was associated with histological differentiation, lymph node metastasis and Duke's stage. However, no significant associations were observed between YAP expression and age, sex and T stage. Downregulation of YAP promoted the proliferation and the inhibited apoptosis of CRC cells, and YAP expression was positively correlated with that of β-catenin in both CRC tissues and cells. Furthermore, YAP expression was upregulated in CRC tissues, which was correlated with tumor progression and prognosis. Therefore, YAP expression may be used as an independent predictor of poor prognosis in patients with CRC, and the underling molecular mechanism may be associated with the combined effect of Hippo and Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer worldwide. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 8 (SNHG8) acts as an oncogene in different types of cancer, including prostate, breast and ovarian cancer. SNHG8 promotes the tumorigenesis of CRC; however, its underlying molecular mechanism remains unclear. The present study aimed to explore the mechanism of SNHG8 on CRC development via various assays, including western blot, pull-down, PCR and immunofluorescence assays. The results of the present study demonstrated that SNHG8 expression was substantially upregulated in primary tumor tissues from The Cancer Genome Atlas dataset. Western blot and immunofluorescence analyses demonstrated that SNHG8 facilitated cell proliferation and autophagy in CRC cells. Notably, the function of SNHG8 in enhancing autophagy was dependent on autophagy-related gene 7 (ATG7). In addition, western blot analysis indicated that the effect of SNHG8 on autophagy in CRC cells was dependent on the miR-588/ATG7 axis. Taken together, the results of the present study suggest that SNHG8 promotes autophagy in CRC cells. [ABSTRACT FROM AUTHOR]

Our previous study showed that adhesion molecule with immunoglobulin like domain 2 (AMIGO2) is a pivotal driver gene of liver metastasis via regulating tumor cell adhesion to liver endothelial cells in mouse models. The aim of the present study was to clarify the role of AMIGO2 in liver metastasis in patients the colorectal cancer (CRC). Two human CRC cell lines, Caco-2 (AMIGO2-low) and HCT116 (AMIGO2-high), were used in this study. AMIGO2-overexpressing Caco-2 and AMIGO2-knockdown HCT116 cells were generated by transfection with an AMIGO2 expression vector or AMIGO2 small interfering RNA, respectively. Cell proliferation, invasion and adhesion to human liver endothelial cells were examined in in vitro studies. Immunohistochemical analysis was also performed to evaluate the association between AMIGO2 expression and liver metastasis in patients with CRC. In vitro studies revealed that cell proliferation, invasion and adhesion to liver endothelial cells were accelerated by upregulation of AMIGO2 expression, but suppressed by downregulation of AMIGO2 expression in human CRC cells. Immunohistochemical analysis using clinical CRC specimens revealed that AMIGO2 expression was associated with the frequency of liver metastasis (P<0.01), but not that of pulmonary metastasis (P=0.611) and peritoneal dissemination (P=0.909). In addition, AMIGO2 expression levels in tumor cells were significantly higher in liver metastatic foci than primary lesions (P=0.012). In conclusion, the present results indicated that AMIGO2 expression may contribute to the formation of liver metastasis in CRC. [ABSTRACT FROM AUTHOR]

Although accumulating evidence has confirmed the potential biological functions of long non-coding RNAs (lncRNAs) as competitive endogenous RNAs (ceRNAs) in colorectal tumorigenesis and progression, few studies have focused on rectosigmoid junction cancer. In the present study, a comprehensive analysis was conducted to explore lncRNA-mediated ceRNA implications and their potential value for prognosis. lncRNA, microRNA (miR/miRNA) and mRNA expression profiles were downloaded from The Cancer Genome Atlas database. Subsequently, a lncRNA-miRNA-mRNA regulatory network was constructed to evaluate the functions of these differentially expressed genes on overall survival (OS) for rectosigmoid junction cancer. As a result, a rectosigmoid junction cancer-specific ceRNA network was successfully constructed with 7 differentially expressed (DE)lncRNAs, 16 DEmiRNAs and 71 DEmRNAs. Among the network, one DElncRNA (small nucleolar RNA host gene 20) and three mRNAs (sodium- and chloride-dependent taurine transporter, fibroblast growth factor 13 and tubulin polyglutamylase TTLL7) were significantly associated with OS (P<0.05). Additionally, two lncRNAs (KCNQ1OT1 and MIR17HG) interacted with most of the DEmiRNAs. Notably, two top-ranked miRNAs (hsa-miR-374a-5p and hsa-miR-374b-5p) associated networks were identified to be markedly associated with the pathogenesis. Furthermore, four DEmRNAs (caveolin-1, MET, filamin-A and AKT3) were enriched in the Kyoto Encylopedia of Gene and Genomes pathway analysis, as well as being included in the ceRNA network. In summary, the present results revealed that a specific lncRNA-miRNA-mRNA network was associated with rectosigmoid junction cancer, providing several molecules that may be used as novel prognostic biomarkers and therapeutic targets., (Copyright: © Zhang et al.)

Long non-coding RNA (Lnc)TCF7 is a novel lncRNA that is involved in tumorigenesis. Previous studies have revealed that lncTCF7 serves an essential role in maintaining cancer stem cell self-renewal; however, the functions of lncTCF7 in colorectal cancer (CRC) remain unknown. Therefore, the present study aimed to investigate the role of lncTCF7 in CRC. LncTCF7 was upregulated in 52/58 CRC tissues, and its expression correlated with tumor size, lymph metastasis and tumor-node-metastasis stage in CRC. Knocking down lncTCF7 in colon cancer cell lines decreased cell proliferation, migration and invasion, while lncTCF7 overexpression showed opposite changes. In addition, lncTCF7 promoted cell proliferation in vivo . LncTCF7 activated the Wnt/β-catenin signaling pathway, which is essential for cancer development. Survival analysis revealed that patients with higher expression of lncTCF7 had significantly worse prognosis compared with patients with low expression. These findings indicate that lncTCF7 regulates CRC progression and support the notion of lncTCF7 as a CRC prognostic marker.