CircSTK3 drives the metastasis of colorectal cancer by regulating epithelial-mesenchymal transition.

Circular RNAs (circRNAs) play crucial roles in malignancies. We aimed to delineate the functions and clinical importance of dysregulated circRNAs in colorectal cancer (CRC). We determined the circRNA expression profile from five CRC and paired adjacent normal tissues using circRNA microarray. We found that a novel circRNA, hsa_circ_0004592 (named circSTK3), was significantly upregulated in CRC tissues and correlated with decreased survival. Loss- and gain-of-function assays revealed that circSTK3 promoted the migration and invasion but not proliferation of cells. Whole genome expression microarray identified potential downstream targets and the regulatory networks of circSTK3; Gene Ontology analysis confirmed circSTK3 involvement in the CRC metastasis phenotype. Abnormal circSTK3 expression affected a subset of genes associated with CRC metastasis and triggered epithelial-mesenchymal transition programming, maintaining a tumor-promoting signature. Moreover, circSTK3 was transcriptionally regulated by CTCF. These findings reveal the functional and prognostic roles of circSTK3 and expose circRNAs as key players in metastasis.

LncRNAs, the Molecules Involved in Communications With Colorectal Cancer Stem Cells.

Colorectal cancer stem cells (CRCSCs) can actively self-renew, as well as having multidirectional differentiation and tumor regeneration abilities. Because the high functional activities of CRCSCs are associated with low cure rates in patients with colorectal cancer, efforts have sought to determine the function and regulatory mechanisms of CRCSCs. To date, however, the potential regulatory mechanisms of CRCSCs remain incompletely understood. Many non-coding genes are involved in tumor invasion and spread through their regulation of CRCSCs, with long non-coding RNAs (lncRNAs) being important non-coding RNAs. LncRNAs may be involved in the colorectal cancer development and drug resistance through their regulation of CRCSCs. This review systematically evaluates the latest research on the ability of lncRNAs to regulate CRCSC signaling pathways and the involvement of these lncRNAs in colorectal cancer promotion and suppression. The regulatory network of lncRNAs in the CRCSC signaling pathway has been determined. Further analysis of the potential clinical applications of lncRNAs as novel clinical diagnostic and prognostic biomarkers and therapeutic targets for colorectal cancer may provide new ideas and protocols for the prevention and treatment of colorectal cancer.

Nomogram to Predict the Occurrence and Prognosis of Distant Metastasis in T1N0 Colon Cancer: A SEER Data-Based Study.

PURPOSE: Distant metastasis (DM) is relatively rare in T1 colon cancer (CC) patients, especially in those with negative lymph node metastasis. The aim of this study was to explore the main clinical factors and build nomogram for predicting the occurrence and prognosis of DM in T1N0 colon cancer patients. METHODS: Patients with T1N0 stage CC were collected from the Surveillance, Epidemiology, and End Result (SEER) database. All patients were divided into development and validation cohorts with the 3:1 ratio. Logistic regressions were performed to analyze the clinical risk factors for DM. Cox regression model was used to identify potential prognostic factors for patients with DM. The performance of nomogram was evaluated by concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves and decision curve analyses (DCAs). Based on cancer-specific survival (CSS), Kaplan-Meier curves were generated and analyzed using Log rank tests. RESULTS: A total of 6770 patients were enrolled in this study, including 428 patients (6.3%) with DM. Age, size, grade, CEA were independent risk factors associated with DM. Age, grade, CEA, surgery and chemotherapy were independent prognostic factors for CSS. Nomograms were applied and C-index, calibration curves, ROC curves and DCA curves proved good discrimination, calibration and clinical practicability of the nomogram in predicting the occurrence and prognosis of DM in T1N0 CC patients. In the DM nomogram, the AUCs for development and validation cohort were 0.901 (95% CI = 0.879-0.922) and 0.899 (95% CI=0.865-0.940), respectively. The calibration curves (development cohort: S: p = 0.712; validation cohort: S: p = 0.681) showed the relatively satisfactory prediction accuracy. Similarly, the AUCs of the nomogram at 1-, 2-, and 3-year were 0.763 (95% CI=0.744-0.782), 0.794 (95% CI=0.775-0.813), and 0.822 (95% CI=0.803-0.841) for the development cohort, and 0.785 (95% CI=0.754-0.816), 0.748 (95% CI=0.717-0.779) and 0.896 (95% CI=0.865-0.927) for the validation cohort in the CSS nomogram. The C-indices of the development and validation cohort were 0.718 (95% CI=0.639-0.737) and 0.712 (95% CI=0.681-0.743). CONCLUSION: The population-based nomogram could help clinicians predict the occurrence and prognosis of DM in T1N0 CC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.

The late positive potential as a neurocognitive index of emotion regulatory flexibility.

A growing body of research has examined regulatory flexibility as the ability to dynamically modulate emotional expression and experience (Bonanno & Burton, 2013). The late positive potential (LPP), an event-related potential reflecting processing of emotionally-evocative stimuli, is sensitive to emotion regulation (ER) or the psychological processes that underlie the experience, expression, and management of emotions. However, few studies have used the LPP to index regulatory flexibility or tested its association with self-reported emotional well-being and ER. The results of the current study showed that regulatory flexibility indexed via the LPP was associated with self-reported use of specific ER strategies. Further, greater regulatory flexibility measured as the full LPP regulatory range (indexed following prompts to enhance and suppress emotional responses to stimuli) was specifically and uniquely associated with greater self-reported coping flexibility. Findings provide preliminary support for this neurocognitive approach to conceptualizing and assessing regulatory flexibility.

Latent variable analysis of positive and negative valence processing focused on symptom and behavioral units of analysis in mood and anxiety disorders.

BACKGROUND: Mood and anxiety disorders are highly heterogeneous and their underlying pathology is complex. The Research Domain Criteria (RDoC) approach seeks to establish dimensionally and neuroscience-based descriptions of psychopathology that may inform better classification and treatment approaches. The current investigation sought to determine the latent variables underlying positive and negative valence processing in terms of symptoms and behavioral units of analysis. METHOD: As part of an ongoing study, individuals with mood and anxiety problems were recruited largely from primary care clinics at UCLA (n=62) and UCSD (n=58). These participants underwent a comprehensive symptomatic and behavioral assessment. An implicit approach avoidance task and a modified dot probe detection task were used to measure positive and negative valence processing. RESULTS: Principal components analysis with varimax rotation identified four symptom components, three behavioral components for the dot probe task, and two behavioral components for the implicit approach avoidance task. These components yielded two meta-components consisting of: negative valence symptoms, negative approach bias, and high sustained, selective attention; and positive valence symptoms, positive approach bias, and slow selective or sustained attention. The components did not differ between males and females, nor by age or medication status. LIMITATIONS: The limitations are: (1) relatively small sample, (2) exploratory analysis strategy, (3) no test/re-test data, (4) no neural circuit analysis, and (5) limited reliability of behavioral data. CONCLUSIONS: These preliminary data show that positive and negative valence processing domains load on independent dimensions. Taken together, multi-level assessment approaches combined with advanced statistical analyses may help to identify distinct positive and negative valence processes within a clinical population that cut across traditional diagnostic categories.

Food quality and motivation: a refined low-fat diet induces obesity and impairs performance on a progressive ratio schedule of instrumental lever pressing in rats.

INTRODUCTION: Purified high-fat diet (HFD) feeding causes deleterious metabolic and cognitive effects when compared with unrefined low-fat diets in rodent models. These effects are often attributed to the diet's high content of fat, while less attention has been paid to other mechanisms associated with the diet's highly refined state. Although the effects of HFD feeding on cognition have been explored, little is known about the impact of refined vs. unrefined food on cognition. We tested the hypothesis that a refined low-fat diet (LFD) increases body weight and adversely affects cognition relative to an unrefined diet. MATERIALS AND METHODS: Rats were allowed ad libitum access to unrefined rodent chow (CON, Lab Diets 5001) or a purified low-fat diet (REF, Research Diets D12450B) for 6 months, and body weight and performance on an instrumental lever pressing task were recorded. RESULTS: After six months on their respective diets, group REF gained significantly more weight than group CON. REF rats made significantly fewer lever presses and exhibited dramatically lower breaking points than CON rats for sucrose and water reinforcement, indicating a chronic reduction of motivation for instrumental performance. Switching the rats' diet for 9 days had no effect on these measures. CONCLUSIONS: Diet-induced obesity produces a substantial deficit in motivated behavior in rats, independent of dietary fat content. This holds implications for an association between obesity and motivation. Specifically, behavioral traits comorbid with obesity, such as depression and fatigue, may be effects of obesity rather than contributing causes. To the degree that refined foods contribute to obesity, as demonstrated in our study, they may play a significant contributing role to other behavioral and cognitive disorders.