Transcribed-ultraconserved regions (T-UCRs), which contain conserved sequences with 100% identity across human, rat and mouse species, are a novel category of functional RNAs. The human transformer 2β gene (TRA2B) encodes a UCR that spans exon 2 (276 bp) and its neighboring introns. Among five spliced RNA variants (TRA2β1-5) transcribed from the TRA2B gene, only TRA2β4 contains the conserved exon 2. TRA2β4 is overexpressed in colon cancer cells and accelerates cell growth by blocking the transcription of CDKN1A. However, the mechanisms underlying the overexpression of TRA2β4 in colon cancer cells are unknown. Using biotinylated RNA pull-down assays followed by liquid chromatography-mass spectrometric analysis, we identified nucleolin as a TRA2β4-binding protein. Knockdown of nucleolin reduced the nuclear retention of TRA2β4 and accelerated its degradation in the cytoplasm, whereas nucleolin overexpression increased TRA2β4 levels and its mitogenic activity. Nucleolin directly bound to TRA2β4 exon 2 via the glycine/arginine-rich (GAR) domain. Overexpression of GAR-deficient nucleolin failed to increase TRA2β4 expression and growth of colon cancer cells. RNA fluorescence in situ hybridization showed that TRA2β4 co-localized with nucleolin in nuclei but not with the mutant lacking GAR. Our results suggest that specific interactions between nucleolin and UCR-containing TRA2β4 may be associated with abnormal growth of colon cancer cells.

Colon cancer stem cells (CSCs), which are highly capable of self-renewal and proliferation, are involved in colon tumorigenesis and response to therapy. CD133 is considered the most robust surface marker for colorectal cancer stem cells. Although the TP53 gene is frequently mutated in colon cancer, it remains not fully understood whether and how tumor protein p53 (p53) is associated with CD133 expression in colon cancer cells. In the present study, the expression of the CSC biomarker CD133 was investigated in terms of p53 status in colorectal carcinoma HCT116 cells. p53 wild-type HCT116 (HCT116 p53+/+) and depleted HCT116 (HCT116 p53-/-) cells were used throughout this study. Cells carrying the CSC biomarkers CD133 and CD44 were examined by flow cytometry. A dual-luciferase reporter assay was employed to further confirm the transcriptional regulation of the CD133 promoter by p53. The results demonstrated that there was a significant difference in the % of CD133-positive cells between the HCT116 p53+/+ cell line (84.84±0.05%) and the HCT116 p53-/- cell line (4.13±0.02%). The mRNA expression levels of CD133 in HCT116 p53+/+ cells were also significantly higher compared with HCT116 p53-/- cells. Knockdown of p53 by specific small interfering RNA greatly reduced the expression of CD133 in HCT116 p53+/+ cells. Transcription factor binding site analysis indicated that there are several p53 binding elements in the CD133 promoter region. A dual-luciferase reporter assay further demonstrated the transcriptional activation of CD133 promoter by p53. In conclusion, these results suggest that p53 positively regulates the expression of CSC marker CD133 in the HCT116 human colon colorectal cancer cell line. p53 may be involved in the initiation and maintenance of colorectal cancer stem cells through regulating the expression of CD133.

Colorectal carcinoma (CRC) is the second leading cause of cancer mortality worldwide. O-glycosylated mucins at the cell surface of colonic mucosa exhibit alterations in cancer and are involved in fundamental biological processes, including invasion and metastasis. Certain members of the GalNAc-transferase family may be responsible for these changes and are being investigated as novel biomarkers of cancer. In the present study the prognostic significance of GalNAc-T6 was investigated in patients with CRC patients. GalNAc-T6 expression was observed in all three colon cancer cell lines analyzed by reverse transcription-polymerase chain reaction, immunofluorescence and flow cytometry. A cohort of 81 colon cancer specimens was analyzed by immunohistochemical staining using MAb T6.3. It was demonstrated that GalNAc-T6 was expressed in 35/81 (43%) cases of colon cancer but not in the normal colonic mucosa. No association was observed with the clinical-pathologic parameters. However, patients expressing GalNAc-T6 had a significantly increased overall survival (median, 58 months; P<0.001) compared with GalNAc-T6 negative patients, especially those with advanced disease. These results suggest that GalNAc-T6 expression predicts an improved outcome in patients with CRC. The molecular mechanism underlying the less aggressive behavior of colon cancer cells expressing GalNAc-T6 remains to be elucidated.

The aim of the present study was to investigate more colon cancer-related genes in different stages. Gene expression profile E-GEOD-62932 was extracted for differentially expressed gene (DEG) screening. Series test of cluster analysis was used to obtain significant trending models. Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, functional and pathway enrichment analysis were processed and a pathway relation network was constructed. Gene co-expression network and gene signal network were constructed for common DEGs. The DEGs with the same trend were clustered and in total, 16 clusters with statistical significance were obtained. The screened DEGs were enriched into small molecule metabolic process and metabolic pathways. The pathway relation network was constructed with 57 nodes. A total of 328 common DEGs were obtained. Gene signal network was constructed with 71 nodes. Gene co-expression network was constructed with 161 nodes and 211 edges. ABCD3, CPT2, AGL and JAM2 are potential biomarkers for the diagnosis of colon cancer.

As targeted drug therapy is increasingly applied in the treatment of colon cancer, understanding and managing the adverse reactions of patients is becoming increasingly important. The present review examines the mechanisms of and adverse reactions to the most commonly used targeted drugs for colon cancer, and discusses methods of coping with these adverse reactions. Approved targeted drugs for metastatic colon cancer include monoclonal antibodies targeting vascular endothelial growth factor (VEGF), including bevacizumab, ziv-aflibercept and regorafenib, and monoclonal antibodies targeting epithelial growth factor receptor (EGFR), including cetuximab and panitumumab. The present review assesses the major adverse effects of these drugs and methods of dealing with reactions to them. VEGF inhibitors primarily result in cardiovascular and kidney problems. Meanwhile, EGFR receptor inhibitors are frequently reported to cause rashes, diarrhea and hypertension, and are reviewed from the point of view of resulting electrolyte disturbances.

The aim of the present study was to evaluate the safety and feasibility of single-port laparoscopic multivisceral resection (S-MVR) for locally advanced left colon cancer. S-MVR is a challenging technique and to the best of our knowledge this is the first report of S-MVR for left colon cancer invading or adhering to neighboring organs. A retrospective review was conducted of patients who underwent laparoscopic multivisceral resection for locally advanced left colon cancer invading or adhering to neighboring organs from January 2008 to December 2014. Short-term and long-term outcomes were analyzed between groups of patients who underwent S-MVR and multi-port laparoscopic multivisceral resection (M-MVR) retrospectively. A total of 14 patients underwent S-MVR and 15 patients underwent M-MVR. There were no significant differences between groups in terms of operative factors and postoperative complications. The length of hospital stay was significantly shorter in the S-MVR group compared with the M-MVR group (P=0.048). Three-year overall survival was 61.9% in the S-MVR group (n=14). In patients with stage II (P=0.600) and III (P=0714) disease the three-year overall and disease-free survival was 81.8 and 58.3% in the S-MVR group and 80.0 and 70% in the M-MVR groups over a median follow-up of 34 months. In conclusion, S-MVR for locally advanced left colon cancer is safe and feasible in selected patients.

Sphingosine kinase 1 (SphK1) is a master kinase that catalyzes the synthesis of sphingosine 1 phosphate and participates in the regulation of cell proliferation and autophagy. The present study aimed to assess the effects of the activation of the SphK1/extracellular signal-regulated kinase (ERK)/phosphorylated (p-)ERK pathway in the regulation of autophagy in colon cancer (HT-29) cells. Inverted fluorescence microscopy was used to detect the expression of green fluorescent protein (GFP) in the SphK1-overexpressing HT-29 cells [SphK1(+)-HT-29] and the negative control HT-29 cells (NC-HT-29). Western blotting was used to detect the protein expression levels of SphK1, ERK1/2, p-ERK1/2, as well as those of the autophagy-associated markers LC3A, ATG5, and ULK1. Protein localization and expression of the LC3A antibody were detected by immunofluorescence. The results demonstrated that GFP was similarly expressed in SphK1(+)-HT-29 and NC-HT-29 cells. However, significantly increased SphK1 mRNA and protein expression levels were detected in SphK1(+)-HT-29 cells compared with in NC-HT-29 cells, which resulted in upregulated ERK/p-ERK. Furthermore, the protein expression levels of the three autophagy-associated markers increased. LC3A protein was localized in the cytoplasm of SphK1(+)-HT-29 cells, indicating autophagy. In summary, the findings of the present study suggested that activation of the SphK1/ERK/p-ERK pathway promotes autophagy in colon cancer HT-29 cells.

Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy efficacy. In the present study, 6-O-angeloylplenolin repressed the overexpression of ATP binding cassette subfamily B member 1 (MDR1) and increasing the intracellular concentration of anticancer drugs. A reduction in P-glycoprotein expression (encoded by MDR1) was observed in parallel with a decline in mRNA expression in vincristine-resistant HCT (HCT-8/VCR) cells treated with 6-O-angeloylplenolin. In addition, 6-O-angeloylplenolin suppressed the activity of the MDR1 gene promoter. Treatment with 6-O-angeloylplenolin also decreased the amount of the specific protein complex that interacted with the MDR1 gene promoter in HCT-8/VCR cells, potentially leading to the suppression of MDR1 expression. Treatment with 6-O-angeloylplenolin inhibited the nuclear translocation of Y-box binding protein-1 in HCT-8/VCR cells treated with 6-O-angeloylplenolin, contributing to the negative regulation of MDR1. Finally, 6-O-angeloylplenolin reversed VCR resistance in an HCT/VCR xenograft model. In conclusion, 6-O-angeloylplenolin exhibited a MDR-reversing effect by downregulating MDR1 expression and could represent a novel adjuvant agent for chemotherapy.

It has previously been reported that cardamonin is able to regulate glycometabolism and vasodilation whilst also exhibiting anti-inflammatory and antitumor properties. The antitumor effect of cardamonin is multifaceted, and so it is necessary to investigate the antitumor mechanisms of cardamonin at the molecular level. Cardamonin alters chemotherapy-resistant colon cancer cell growth; however, the underlying mechanism is unknown. The present study was conducted to investigate the effect of cardamonin on chemotherapy-resistant colon cancer cells and the possible mechanisms of action. Cardamonin significantly suppressed the growth of chemotherapy-resistant colon cancer cells, induced apoptosis and promoted caspase-3/9 activity and Bax protein expression in 5-fluorouracil (5-FU)-resistant HCT-116 cells. Cardamonin significantly suppressed c-MYC, octamer-binding transcription factor 4, cyclin E, testes-specific protease 50 and nuclear factor-κB protein expression in 5-FU-resistant HCT-116 cells. The findings of the present study demonstrate that cardamonin suppresses chemotherapy-colon cancer cell via the NF-κB pathway in vitro.