Search

Background: To investigate the factors associated with acute kidney injury (AKI) in postoperative colorectal cancer (CRC) patients and develop a risk prediction model., Methods: The clinical data of 389 CRC patients were retrospectively analyzed. The patients were divided into AKI (n = 30) and non-AKI groups (n = 359) according to KDIGO diagnostic criteria. Demographic data, the presence of underlying diseases, perioperative conditions and related examination results were compared between the two groups. Binary logistic regression was used to analyze the independent risk factors for postoperative AKI, and a risk prediction model was established. And a verification group (94 patients) was used to verify the model., Results: 30 patients (7.71%) with CRC had postoperative AKI. Binary logistic regression analysis showed that preoperative combined hypertension, preoperative anemia, inadequate intraoperative crystalloid infusion, low intraoperative minimum mean arterial pressure (MAP) and moderate to severe postoperative decline in hemoglobin (Hb) levels were independent risk factors. The risk prediction model developed was expressed as Logit P = - 0.853 + 1.228 * preoperative combined hypertension + 1.275 *preoperative anemia - 0.002 * intraoperative crystalloid infusion (ml) - 0.091 * intraoperative minimum MAP (mmHg) + 1.482 * moderate to severe postoperative decline in Hb levels. In Hosmer-Lemeshow test, χ 2  = 8.157, P = 0.718 showed that the fitting effect was good. The area under ROC curve was 0.776 (95% CI 0.682-0.871, P < 0.001), with a prediction threshold of 1.570, a sensitivity of 63.3% and a specificity of 88.9%. The sensitivity and specificity of the verification group were 65.8% and 86.1%., Conclusions: Preoperative combined hypertension, preoperative anemia, inadequate intraoperative crystalloid infusion, low intraoperative minimum MAP, and moderate to severe postoperative decline in Hb levels were independent risk factors for AKI development in CRC patients. The prediction model can effectively predict the occurrence of postoperative AKI in patients with CRC., (© 2023. Italian Society of Surgery (SIC).)

Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Cancer-associated fibroblasts (CAFs) have been intensively studied in recent studies with aims of finding more concrete evidence on their mechanism of involvement in tumor progression, which is currently unknown. CAFs can secrete exosomes which are loaded with proteins, lipids and RNAs, all of which affect tumor microenvironment. The present study identified microRNA-93-5p (miR-93-5p) as a novel exosomal cargo responsible for the pro-tumorigenic effects of CAFs on colorectal cancer (CRC)., Methods: CAFs and normal fibroblasts (NFs) were isolated from cancerous tissues and matched with paracancerous tissues that had been surgically resected from CRC patients. The interaction among miR-93-5p, forkhead box A1 (FOXA1) and TGFB3 was identified through ChIP and dual luciferase reporter assays. The proliferation and apoptosis of SW480 cells co-cultured with CAFs-derived exosomes under irradiation were evaluated by CCK-8, colony formation, and flow cytometric assays. Tumorigenesis of SW480 cells in nude mice was assessed under the irradiation., Results: FOXA1 was found to be associated with reduced radioresistance in CRC cells and was verified as a target of miR-93-5p. CAFs-derived exosomes contained higher miR-93-5p than those from NFs, which augmented SW480 cell proliferation and rescued them from radiation-induced apoptosis. miR-93-5p was identified as a mediator of the exosomal effects of CAFs on SW480 cells, possibly through downregulating FOXA1 and upregulating TGFB3. FOXA1 could bind to the promoter of TGFB3, thereby inhibiting nuclear accumulation of TGFB3. Also, CAFs-derived exosomes containing miR-93-5p increased the tumor growth of SW480 cells in irradiated nude mice., Conclusion: The present study identifies miR-93-5p as a specific exosomal cargo that rescues CRC cells against radiation-induced apoptosis.

Objective: To predict and identify the target gene of miR-145, and to explore the underlying mechanism of the inhibition of miR-145 on drug resistance to Oxaliplatin (L-OHP) in human colorectal cancer cells., Methods: L-OHP-resistant human colorectal cancer cell line (HCT116/L-OHP) was established in vitro by exposing to increased concentrations of L-OHP in cell culture medium. MiR-145-mimics and its negative control (NC-miRNA) were transfected into HCT116/L-OHP cells using liposome to establish HCT116/L-OHP mimics over-expressing miR-145 and HCT116/L-OHP NC . The target genes of miR-145 were predicted by bioinformatic analysis, and validated by dual luciferase activity assay. After determination of G protein coupled receptor 98(GPR98) as target gene, corresponding plasmids were constructed and transfected to establish HCT116/L-OHP GPR98 over-expressing GPR98 and HCT116/L-OHP control . HCT116/L-OHP cells over-expressing both GPR98 and miR-145 (HCT116/L-OHP mimics+GPR98 ) were acquired through modification of the binding sites of GPR98 cDNA with miR-145. CCK-8 assay was used to assess the proliferation (A value) and sensitivity to L-OHP (the lower the IC50, the stronger the sensitivity) in HCT116/L-OHP cells. Real-time quantitative PCR was used to measure the mRNA expression of miR-145 and GPR98. Western blot was used to examine the protein expression of GPR98 and drug-resistant associated protein, such as P-glycoprotein (gp), multiple drug-resistance protein 1(MRP1), cancer-inhibition gene PTEN., Results: HCT116/L-OHP cell line was successfully established with IC 50 of (42.34±1.05) mg/L and miR-145 mRNA expression of 0.27±0.04, which was higher than (9.81±0.95) mg/L (t=39.784, P=0.000) and lower than 1.00±0.09 (t=13.021, P=0.000) in HCT116 cells. Based on HCT116/L-OHP cells, HCT116/L-OHP mimics cells were established successfully, with relative miR-145 expression of 10.01±1.05, which was higher than 1.06±0.14 in HCT116/L-OHP NC and 1.00±0.16 in HCT116/L-OHP (F=161.797, P=0.000). GPR98 was identified to be the target gene of miR-145. The relative mRNA and protein expressions of GPR98 in HCT116/L-OHP GPR98 cells were 8.48±0.46 and 1.71±0.09, respectively, which were higher than those in HCT116/L-OHP control (mRNA: 3.65±0.40, protein: 1.21±0.10) and HCT116/L-OHP (mRNA: 3.49±0.35, protein: 1.22±0.08; all P<0.05). The A value was 1.31±0.10, and the relative protein expressions of P-gp and MRP1 were 1.53±0.18 and 1.49±0.20 in HCT116/L-OHP GPR98 cells, which were higher than those in HCT116/L-OHP (A value: 0.82±0.08, relative protein expression: 1.00±0.06 and 1.21±0.13, all P<0.05). The A value was 0.89±0.08, and the relative protein expressions of P-gp and MRP were 1.02±0.24 and 1.38±0.25 in HCT116/L-OHP mimics+GPR98 cells, which were higher than those in HCT116/L-OHP mimics (A value: 0.20±0.05, relative protein expression: 0.20±0.07, 0.55±0.10, all P<0.05). The relative protein expression of PTEN in HCT116/L-OHP GPR98 cells was 0.12±0.03, which was lower than 1.25±0.14 in HCT116/L-OHP cells(P<0.05). In addition, relative protein expressions of P-gp and MRP1 were 1.02±0.24 and 1.38±0.25 in HCT116/L-OHP mimics+GPR98 cells, which were higher than those in HCT116/L-OHP mimics cells (0.20±0.07 and 0.55±0.10), while PTEN expression in HCT116/L-OHP mimics+GPR98 cells was lower as compared to HCT116/L-OHP mimics cells (1.41±0.16 vs. 1.98±0.13, P<0.05)., Conclusion: MiR-145 inhibits drug resistance to L-OHP of HCT116 cells through suppressing the expression of target gene GPR98.

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Deregulation of microRNAs (miRNAs) has been reported to participate in CRC progression. In the present study, we observed downregulation of miR-218 and upregulation of YEATS domain containing 4 (YEATS4) in CRC tissues and in multidrug-resistant HCT-116/L-OHP cells compared with these levels in normal tissues and parental HCT-116 cells, respectively. The results indicated that miR-218 overexpression significantly decreased the IC50 value of oxaliplatin (L-OHP) in the HCT-116/L-OHP cells, and suppression of miR-218 significantly enhanced the IC50 of L-OHP in the HCT-116 cells. Flow cytometric analysis showed that miR-218 overexpression alone promoted cell apoptosis in the HCT-116/L-OHP cells, which was further enhanced in response to L-OHP, and miR-218 inhibition decreased cell apoptosis in the HCT-116 cells following treatment with L-OHP. Western blot analysis indicated that, compared with the small increase observed in HCT-116 cells, the relative LC3 II level in HCT-116/L-OHP cells after lysosome inhibition via chloroquine (CQ) was markedly upregulated following L-OHP treatment, suggesting induction of autophagy. Exposure of HCT-116/L-OHP cells to L-OHP after control mimic transfection increased autophagic flux, as reflected by increased LC3 II levels, while miR-218 overexpression partly reversed L-OHP-mediated LC3 II accumulation. Additionally, both miR-218 overexpression and CQ treatment promoted L-OHP-induced HCT-116/L-OHP cell apoptosis. Molecularly, our results confirmed that miR-218 directly targets the YEATS4 gene and inhibits YEATS4 expression. Furthermore, YEATS4 overexpression without the 3'-untranslated region (3'-UTR) restored miR-218-inhibited YEATS4 and LC3 II expression, and abolished miR-218-stimulated cell viability loss and cell apoptosis increase in response to L-OHP. In conclusion, miR-218 sensitized HCT-116/L-OHP cells to L-OHP-induced cell apoptosis via inhibition of cytoprotective autophagy by targeting YEATS4 expression.

Background: Neuroendocrine carcinoma of the colorectum is a kind of malignant tumor composed of neuroendocrine cells, with a unique hormone synthesis and secretory function. In recent years, more and more attention is being paid to this kind of tumor, with its high malignant potential, poor differentiation, high invasiveness and early metastasis., Objectives: The aim of this study was to evaluate the clinicopathological characteristics and prognosis of neuroendocrine carcinoma of the colorectum., Material and Methods: The clinical data on 49 patients treated for neuroendocrine carcinoma of the colorectum from January 1995 to January 2013 were retrospectively analyzed and relevant scientific literature was investigated., Results: The study subjects included 34 males and 15 females, out of whom 27 patients underwent curative operations, while 18 underwent palliative resections and four others underwent biopsy. All 49 patients underwent adjuvant chemotherapy after operation. Of the 45 resection samples, vascular invasion was found in 33 patients (73.3%) and regional lymph node metastasis was found in 35 patients (77.8%). All the patients were followed up for a period of 3 to 68 months. The 1-year, 3-year and 5-year survival rates were 49.1%, 17.2% and 6.9%, respectively. The patients' survival time was related to the tumor stage, vascular invasion and surgery type (radical or not), but not related to age, gender, tumor size or tumor location., Conclusions: Neuroendocrine carcinoma of the colon lacked specific clinical manifestations, but showed a high degree of malignancy and a poor prognosis. Tumour stage, vascular invasion and surgery type (radical or not) were important factors influencing the prognosis.

Objective: To investigate the role of death associated protein kinase(DAPK) in colon cancer drug-resistance., Methods: Immunohistochemistry was used to detect DAPK expression in colon carcinoma tissues of 61 cases and adjacent tissues of 32 cases. 5-fluorouracil (5-FU)-induced drug-resistant colon cancer cell lines HCT116/5-FU model was established. DAPK-siRNA was transfected into cells to down-regulate the DAPK gene expression (DAPK-siRNA grouyp), FAM-siRNA was transfected as control group, and DAPK over-expression plasmid vectors were constructed to up-regulate the DAPK gene expression(DAPK over-expression group). Real-time quantitative PCR and Western blotting were used to examine the mRNA and protein expression levels of DAPK, multidrug resistance protein (MRP) and P- glycoprotein (P-gp). MTT and flow cytometry were used to detect cell proliferation and apoptosis for cells treated with 5-FU (8 mg/L) and cells without treatment of 5-FU in 3 groups respectively., Results: Positive expression rate of DAPK in colon cancer tissues was significantly lower than that in adjacent normal tissues [18.0% (11/61) vs. 90.6% (29/32), P < 0.05]. Compared with FAM-siRNA group, DAPK mRNA and protein expression levels were significantly lower in DAPK-siRNA group, but significantly higher in DAPK over-expression group (P<0.05). After treatment of 5-FU, cell proliferation was significantly inhibited, but cell apoptosis was significantly increased in DAPK over-expression group compared to FAM-siRNA group (P < 0.05). Cell proliferation and apoptosis were not significantly different between DAPK siRNA and FAM-siRNA groups (all P < 0.05). Compared with FAM-siRNA group, DAPK over-expression could significantly reduce the mRNA and protein levels of MRP and P-gp, whereas DAPK siRNA had no obvious such effects., Conclusion: DAPK can inhibit the proliferation and promote the apoptosis in drug-resistant colon cancer cells, and it probably enhances the sensitivity of cancer cells to drugs by down-regulating the mRNA and protein levels of MRP and P-gp.