Background NOD-like receptors affect multiple stages of cancer progression in many malignancies. NACHT, LRR, and PYD domain-containing protein 7 (NLRP7) is a member of the NOD-like receptor family, although its role in tumorigenesis remains unclear. By analyzing clinical samples, we found that NLRP7 protein levels were upregulated in colorectal cancer (CRC). We proposed the hypothesis that a high level of NLRP7 in CRC may promote tumor progression. Here, we further investigated the role of NLRP7 in CRC and the underlying mechanism. Methods NLRP7 expression in human CRC and adjacent non-tumorous tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The effect of NLRP7 in CRC progression was investigated in vitro and in vivo. Proteins interacting with NLRP7 were identified by immunoprecipitation and mass spectrometry analysis while immunofluorescence staining revealed the cellular location of the proteins. Cellular ubiquitination and protein stability assays were applied to demonstrate the ubiquitination effect on NLRP7. Cloning and mutagenesis were used to identify a lysine acceptor site that mediates NLRP7 ubiquitination. Cytokines/chemokines affected by NLRP7 were identified by RNA sequencing, qRT-PCR, and enzyme-linked immunosorbent assay. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and immunohistochemistry. Results NLRP7 protein levels, but not mRNA levels, were upregulated in CRC, and increased NLRP7 protein expression was associated with poor survival. NLRP7 promoted tumor cell proliferation and metastasis in vivo and in vitro and interacted with ubiquitin-specific protease 10, which catalyzed its deubiquitination in CRC cells. NLRP7 stability and protein levels in CRC cells were modulated by ubiquitination and deubiquitination, and NLRP7 was involved in the ubiquitin-specific protease 10 promotion of tumor progression and metastasis in CRC. K379 was an important lysine acceptor site that mediates NLRP7 ubiquitination in CRC cells. In CRC, NLRP7 promoted the polarization of pro-tumor M2-like macrophages by inducing the secretion of C-C motif chemokine ligand 2. Furthermore, NLRP7 promoted NF-κB nuclear translocation and activation of C-C motif chemokine ligand 2 transcription. Conclusions We showed that NLRP7 promotes CRC progression and revealed an as-yet-unidentified mechanism by which NLRP7 induces the polarization of pro-tumor M2-like macrophages. These results suggest that NLRP7 could serve as a biomarker and novel therapeutic target for the treatment of CRC.
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Background The use of a self-expandable metallic stent (SEMS) as a bridge to surgery has increased for patients with obstructing colorectal cancer. However, relatively few reports have compared SEMS as a bridge to elective surgery for acute malignant obstruction of the right-sided colon (MORC) vs. emergency surgery (ES). This study aimed to evaluate the benefits of elective surgery after SEMS placement vs. ES for patients (including stage IV cases) with acute MORC. Methods Patients with acute MORC who underwent radical resection for a primary tumour from July 2008 to November 2016 at Zhongshan Hospital of Fudan University were retrospectively enrolled. Postoperative short-term outcomes, progression-free survival (PFS), and overall survival (OS) were compared between the SEMS and ES groups. Results In total, 107 patients with acute MORC (35 in the SEMS group and 72 in the ES group) were included for analysis. The Intensive Care Unit admission rate was lower (11.4% vs. 34.7%, P = 0.011), the incidence of complications was reduced (11.4% vs. 29.2%, P = 0.042), and the postoperative length of hospitalisation was significantly shorter (8.23 ± 6.50 vs. 11.18 ± 6.71 days, P = 0.033) for the SEMS group. Survival curves showed no significant difference in PFS (P = 0.506) or OS (P = 0.989) between groups. Also, there was no significant difference in PFS and OS rates between patients with stage II and III colon cancer. After colectomy for synchronous liver metastases among stage IV patients, the hepatectomy rates for the SEMS and ES groups were 85.7% and 14.3%, respectively (P = 0.029). The hazard ratio for colectomy alone vs. combined resection was 3.258 (95% CI 0.858–12.370; P = 0.041). Conclusion Stent placement offers significant advantages in terms of short-term outcomes and comparable prognoses for acute MORC patients. For synchronous liver metastases, SEMS placement better prepares the patient for resection of the primary tumour and liver metastasis, which contribute to improved survival.
Background: Colorectal cancer (CRC) is the third most common cause of cancer deaths worldwide. Numerous studies have reported that circular RNAs (circRNAs) have important functions in CRC. It was first thought that circRNAs were non-coding RNA; however, more recently they were discovered to encode peptides and play a pivotal role in cancer development and progression. It was shown that most circRNAs possess coding potential; however, not all of them can truly encode peptides. Therefore, a practical strategy to scan for coding circRNAs is needed.Method: Sequence analyses included open reading frame (ORF) prediction, coding peptide prediction, and the identification of unique sequences. Then, experimental assays were used to verify the coded peptides, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was introduced to detect sequences of circRNAs with coding potential, and Western blot was used to identify the encoded peptides. Finally, the functions of the circRNAs were primarily explored.Result: An efficient strategy for searching circRNAs with coding potential was created. We verified this schedule using public databases and LC-MS/MS, then two of these circRNAs were selected for further verification. We used commercial antibodies that can also identify the predicted peptides to test the coded peptides. The functions of the circRNAs were explored primarily, and the results showed that they were mainly involved in the promotion of proliferation and invasion ability.Discussion: We have constructed an efficient strategy of scanning circRNAs with coding potential. Our strategy helped to provide a more convenient pathway for identifying circRNA-derived peptides, which can be a potential therapeutic target or a diagnostic biomarker.
Background: The use of a self-expandable metallic stent (SEMS) as a bridge to surgery has increased for patients with obstructing colorectal cancer. However, relatively few reports have compared SEMS as a bridge to elective surgery for acute malignant obstruction of the right-sided colon (MORC) vs. emergency surgery (ES). This study aimed to evaluate the benefits of elective surgery after SEMS placement vs. ES for patients (including stage IV cases) with acute MORC.Methods: Patients with acute MORC who underwent radical resection for a primary tumour from July 2008 to November 2016 at Zhongshan Hospital of Fudan University were retrospectively enrolled. Postoperative short-term outcomes, progression-free survival (PFS), and overall survival (OS) were compared between the SEMS and ES groups.Results: In total, 107 patients with acute MORC (35 in the SEMS group and 72 in the ES group) were included for analysis. The Intensive Care Unit admission rate was lower (11.4% vs. 34.7%, P = 0.011), the incidence of complications was reduced (11.4% vs. 29.2%, P = 0.042), and the postoperative length of hospitalisation was significantly shorter (8.23 ± 6.50 vs. 11.18 ± 6.71 days, P = 0.033) for the SEMS group. Survival curves showed no significant difference in PFS (P = 0.506) or OS (P = 0.989) between groups. Also, there was no significant difference in PFS and OS rates between patients with stage II and III colon cancer. After colectomy for synchronous liver metastases among stage IV patients, the hepatectomy rates for the SEMS and ES groups were 85.7% and 14.3%, respectively (P = 0.029). The hazard ratio for colectomy alone vs. combined resection was 3.258 (95% CI 0.858–12.370; P = 0.041).Conclusion: Stent placement offers significant advantages in terms of short-term outcomes and comparable prognoses for acute MORC patients. For synchronous liver metastases, SEMS placement better prepares the patient for resection of the primary tumour and liver metastasis, which contribute to improved survival.
Background: The use of a self-expandable metallic stent (SEMS) as a bridge to surgery has increased for patients with obstructing colorectal cancer. However, relatively few reports have compared SEMS as a bridge to elective surgery for acute malignant obstruction of the right-sided colon (MORC) vs. emergency surgery (ES). This study aimed to evaluate the benefits of elective surgery after SEMS placement vs. ES for patients (including stage IV cases) with acute MORC.Methods: Patients with acute MORC who underwent radical resection for a primary tumour from July 2008 to November 2016 at Zhongshan Hospital of Fudan University were retrospectively enrolled. Postoperative short-term outcomes, progression-free survival (PFS), and overall survival (OS) were compared between the SEMS and ES groups.Results: In total, 107 patients with acute MORC (35 in the SEMS group and 72 in the ES group) were included for analysis. The Intensive Care Unit admission rate was lower (11.4% vs. 34.7%, P = 0.011), the incidence of complications was reduced (11.4% vs. 29.2%, P = 0.042), and the postoperative length of hospitalisation was significantly shorter (8.23 ± 6.50 vs. 11.18 ± 6.71 days, P = 0.033) for the SEMS group. Survival curves showed no significant difference in PFS (P = 0.506) or OS (P = 0.989) between groups. Also, there was no significant difference in PFS and OS rates between patients with stage II and III colon cancer. After colectomy for synchronous liver metastases among stage IV patients, the hepatectomy rates for the SEMS and ES groups were 85.7% and 14.3%, respectively (P = 0.029). The hazard ratio for colectomy alone vs. combined resection was 3.258 (95% CI 0.858–12.370; P = 0.041).Conclusion: Stent placement offers significant advantages in terms of short-term outcomes and comparable prognoses for acute MORC patients. For synchronous liver metastases, SEMS placement better prepares the patient for resection of the primary tumour and liver metastasis, which contribute to improved survival.
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