MicroRNA-93 (miR-93) is involved in several carcinoma progressions. It has been reported that miR-93 acts as a promoter or suppressor in different tumors. However, till now, the role of miR-93 in colon cancer is unclear. Herein, we have found that expression of miR-93 was lower in human colon cancer tissue and colorectal carcinoma cell lines compared with normal colon mucosa. Forced expression of miR-93 in colon cancer cells inhibits colon cancer invasion, migration, and proliferation. Furthermore, miR-93 may downregulate the Wnt/β-catenin pathway, which was confirmed by measuring the expression level of the β-catenin, axin, c-Myc, and cyclin-D1 in this pathway. Mothers against decapentaplegic homolog 7 (Smad7), as an essential molecular protein for nuclear accumulation of β-catenin in the canonical Wnt signaling pathway, is predicted as a putative target gene of miR-93 by the silico method and demonstrated that it may be suppressed by targeting its 3'UTR. These findings showed that miR-93 suppresses colorectal cancer development via downregulating Wnt/β-catenin, at least in part, by targeting Smad7. This study revealed that miR-93 is an important negative regulator in colon cancer and suggested that miR-93 may serve as a novel therapeutic agent that offers benefits for colon cancer treatment.
Purpose: While there are no clear indications of whether central lymph node dissection is necessary in patients with T1-T2, non-invasive, clinically uninvolved central neck lymph nodes papillary thyroid carcinoma (PTC), this study seeks to develop and validate models for predicting the risk of central lymph node metastasis (CLNM) in these patients based on machine learning algorithms.Methods: This is a retrospective study comprising 1,271 patients with T1-T2 stage, non-invasive, and clinically node negative (cN0) PTC who underwent surgery at the Department of Endocrine and Breast Surgery of The First Affiliated Hospital of Chongqing Medical University from February 1, 2016, to December 31, 2018. We applied six machine learning (ML) algorithms, including Logistic Regression (LR), Gradient Boosting Machine (GBM), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Decision Tree (DT), and Neural Network (NNET), coupled with preoperative clinical characteristics and intraoperative information to develop prediction models for CLNM. Among all the samples, 70% were randomly selected to train the models while the remaining 30% were used for validation. Indices like the area under the receiver operating characteristic (AUROC), sensitivity, specificity, and accuracy were calculated to test the models' performance.Results: The results showed that ~51.3% (652 out of 1,271) of the patients had pN1 disease. In multivariate logistic regression analyses, gender, tumor size and location, multifocality, age, and Delphian lymph node status were all independent predictors of CLNM. In predicting CLNM, six ML algorithms posted AUROC of 0.70–0.75, with the extreme gradient boosting (XGBoost) model standing out, registering 0.75. Thus, we employed the best-performing ML algorithm model and uploaded the results to a self-made online risk calculator to estimate an individual's probability of CLNM (https://jin63.shinyapps.io/ML_CLNM/).Conclusions: With the incorporation of preoperative and intraoperative risk factors, ML algorithms can achieve acceptable prediction of CLNM with Xgboost model performing the best. Our online risk calculator based on ML algorithm may help determine the optimal extent of initial surgical treatment for patients with T1-T2 stage, non-invasive, and clinically node negative PTC.
d MicroRNAs (miRNAs) are dysregulated in many types of malignant diseases, including colorectal cancer. miRNA 30a (miR-30a) is a member of the miR-30 family and has been implicated in many types of cancers. In this study, we determined the expression of miR-30a in human colon cancer tissues and cell lines. miR-30a was found to be significantly downregulated in both the tissues and cell lines. Furthermore, overexpression of miR-30a inhibited, while silencing of miR-30a promoted, cell proliferation, migration, and invasion in vitro. Consistently, stable overexpression of miR-30a suppressed the growth of colon cancer cell xenografts in vivo. Moreover, bioinformatic algorithms and luciferase reporter assays revealed that insulin receptor substrate 2 (IRS2) is a direct target of miR-30a. Further functional studies suggested that repression of IRS2 by miR-30a partially mediated the tumor suppressor effect of miR-30a. In addition, miR-30a inhibited constitutive phosphorylation of Akt by targeting IRS2. Additionally, clinicopathological analysis indicated that miR-30a has an inverse correlation with the staging in patients with colon cancer. Taken together, our study provides the first evidence that miR-30a suppressed colon cancer cell growth through inhibition of IRS2. Thus, miR-30a might serve as a promising therapeutic strategy for colon cancer treatment. Colorectal cancer (CRC) is the third most common cancer in males and females, with an estimated 142,820 new cases and 50,830 deaths in the United States in 2013. The overall CRC incidence is 5% in the general population, and the 5-year survival rate ranges from 40% to 60% (1). Despite the improvement of currently available treatment strategies, including surgical resection, radiotherapy, and chemotherapy, the survival rate of patients with CRC has changed little over the past 10 years. Almost 50% of CRC patients will die of the disease, mainly due to metastasis to the liver. Thus, it is imperative to achieve earlier diagnosis and better tailoring of treatments to improve CRC outcomes.MicroRNAs (miRNAs) are a family of endogenous small noncoding RNAs that regulate gene expression via the sequence-specific base pairing on the 3= untranslated regions (3= UTRs) of target mRNAs, resulting in mRNA cleavage or translation inhibition (2). More than 30% of the protein-coding genes are controlled by miRNAs, as indicated by bioinformatics predictions. miRNAs are involved in a plethora of biological processes, such as proliferation, migration, invasion, and apoptosis (3, 4). In recent years, miRNAs have been recognized as critical regulators in development and progression of cancer, including CRC (5-8).miRNA 30a (miR-30a) is a member of the miR-30 family, which consists of six distinct mature miRNA sequences: miR-30a/ miR-30c-2, miR-30d/miR-30b, and miR-30e/miR-30c-1 (9). There is considerable evidence suggesting that the dysregulation of miR-30a is correlated with several types of malignant tumors, including breast cancer, lung cancer, thyroid cancer, gastric cancer, and leuke...
BackgroundLeucine-rich α-2-glycoprotein-1 (LRG1) is differentially expressed in many kinds of diseases including cancer, however, it has not been thoroughly studied yet.PurposeThe objective of this study was to detect the expression and potential mechanism of LRG1 in colorectal cancer (CRC). In our study, we examined LRG1 levels in CRC tissue and plasma with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effect of LRG1 on cancer cells was detected with transwell and MTT assays.ResultsThe average plasma LRG1 level in CRC was significantly higher than in polyp group (P=0.002) and healthy controls (P<0.001). Second, plasma LRG1 was positively associated with CA19-9 (r=0.133, P=0.039) and neutrophil ratio (r=0.403, P<0.001). Third, plasma LRG1 of stage IV patients was dramatically different from that of stage I, stage II or stage III patients (P<0.001). LRG1 mRNA expression levels were about 2-fold higher in CRCs compared to normal tissues (P<0.001). And levels of plasma LRG1 were found to be a risk factor in CRC in univariate survival analysis of colorectal prognosis (P=0.013, hazard ratio [HR]=1.803, 95% CI: 1.521–2.137), and multivariate analysis showed that LRG1 was an independent risk factor (P<0.001, HR=1.492, 95% CI: 1.223–1.820). The patients with higher plasma LRG1 value presented with poorer outcome (P=0.013). Functional experiments showed that LRG1 could promote the invasion and growth ability of cells. LRG1 was increased in plasma and tissue compared with that of controls and LRG1 may predict prognosis of CRC patients and LRG1 maybe a tumor promoter.ConclusionLRG1 is increased in CRC patients and might serve as a tumor promoter.
Uncontrolled Wnt signaling causes leukemia. Inactivation of Wnt antagonists could play an important role in leukemia progression by activating the Wnt/β-catenin pathway. Wnt inhibitory factor-1 (WIF1) is one of the important Wnt antagonists. Few miRNAs have been reported to directly target this gene in hematopoiesis. Here, we observed that miR-181a-5p expression was markedly overexpressed in several leukemia cell lines and acute lymphoblastic leukemia (ALL) samples compared with that noted in normal peripheral blood mononuclear cells. MTT assays, soft agar colony formation assays and flow cytometry analysis collectively showed that ectopic expression of miR-181a-5p induced ALL cell growth and proliferation. Furthermore, a mechanistic study disclosed that miR-181a-5p directly downregulated WIF1 expression by binding to its 3'-UTR, and further activated Wnt/β‑catenin signaling. These findings provide a novel mechanistic insight into the role of miR-181a-5p in ALL cell growth and proliferation and implicate miR-181a-5p as an attractive candidate for ALL therapy.
Background: The aim of the present study was to evaluate the presentation, clinical course and outcome between children and young adults with differentiated thyroid cancer (DTC) treated in our hospital. Materials and Methods: The medical records of 145 patients with DTC who underwent surgery followed by radioiodine and thyroid hormone (TSH) suppression were retrospectively reviewed. The follow up was between January 2006 and June 2012. These patients consisted of 38 children (age≤18y) and 107 young adult patients (age≤30y). The clinical characteristics and outcome were analyzed and compared, and the progression-free survival (PFS) was evaluated using the Kaplan-Meier method. Results: At initial diagnosis, a greater degree of extra thyroidal extension was found in children than adults patients (p<0.001). However, there was no significant difference between the two groups with regard to the tumor size and the presence of lymph node or distant metastasis (p=0.172, p=0.050 and p=0.068, respectively). The extent of surgery and the cumulative or mean dose of radioiodine were similar in both groups. During the follow up, the overall survival rate was 100% for both groups, and the PFS rate was similar in children and in young adults group (log rank test, χ 2 =0.126, p=0.723). Conclusions: In comparison to the young adult patients, DTC in children presents with more aggressive behavior, but outcomes are similar between the two groups after the intensive management of surgery followed by radioiodine and TSH suppression therapy.
BackgroundInflammation has been recognized as a key feature of both type 2 diabetes mellitus (T2DM) and atherosclerosis. However, the relationships between circulating levels of novel adipose tissue-derived inflammatory factors, including resistin, vaspin, and visfatin, and the severity of atherosclerosis have not been determined. Moreover, the associations between these inflammatory factors and obesity and insulin resistance in elderly patients remain to be clarified.MethodsA cross-sectional study of 256 elderly patients with T2DM admitted in our center was performed. Baseline circulating levels of resistin, vaspin and visfatin were measured with enzyme-linked immunosorbent assays. Ultrasonic evaluations of the carotid arteries of the patients were performed to reflect the severity of systemic atherosclerosis. Patients were classified as having mild, moderate, or severe atherosclerosis according to the results of carotid ultrasonic examination. Circulating levels of the inflammatory factors listed above also were correlated with body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR).ResultsWith more severe carotid atherosclerosis, circulating levels of resistin (mild: 2.01 ± 0.23; moderate: 2.89 ± 1.01; severe: 3.12 ± 1.12; p < 0.05) and visfatin (mild: 11.63 ± 7.48; moderate: 15.24 ± 2.19; severe: 17.54 ± 2.98; p < 0.05) gradually increased, while level of vaspin decreased (mild: 317 ± 23.12; moderate: 269 ± 32.12; severe: 229 ± 14.24; p < 0.05). Subsequent results of Pearson coefficient analyses indicated that all of the tested adipose tissue-derived inflammatory factors were positively correlated with the BMI and HOMA-IR of the patients (all p < 0.05), even after adjustment for hs-CRP.ConclusionsThe adipose tissue-derived inflammatory factors resistin, vaspin and visfatin may be involved in the pathogenesis of atherosclerosis in elderly T2DM patients.
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