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Hongwei Liu Junming Bi Wei Dong Meihua Yang Juanyi Shi Ning Jiang Tianxin Lin Jian Huang 《Molecular cancer》2018,17(1):161
Background
Increasing evidence has revealed that circular RNAs (circRNAs) play crucial roles in cancer biology. However, the role and underlying regulatory mechanisms of circFNDC3B in bladder cancer (BC) remain unknown.Methods
A cell invasion model was established by repeated transwell assays, and invasion-related circRNAs in BC were identified through an invasion model. The expression of circFNDC3B was detected in 82 BC tissues and cell lines by quantitative real-time PCR. Functional assays were performed to evaluate the effects of circFNDC3B on proliferation, migration and invasion in vitro-, and on tumorigenesis and metastasis in vivo. The relationship between circFNDC3B and miR-1178-3p was confirmed by fluorescence in situ hybridization, pull-down assay and luciferase reporter assay.Results
In the present study, we identified a novel circRNA (circFNDC3B) through our established BC cell invasion model. We found that circFNDC3B was dramatically downregulated in BC tissues and correlated with pathological T stage, grade, lymphatic invasion and patients’ overall survival rate. Functionally, overexpression of circFNDC3B significantly inhibited proliferation, migration and invasion both in vitro and in vivo. Mechanistically, circFNDC3B could directly bind to miR-1178-3p, which targeted the 5′UTR of the oncogene G3BP2. Moreover, circFNDC3B acted as a miR-1178-3p sponge to suppress G3BP2, thereby inhibiting the downstream SRC/FAK signaling pathway.Conclusions
CircFNDC3B may serve as a novel tumor suppressive factor and potential target for new therapies in human BC.2.
Purpose
To explore the role of miR-33b in colorectal cancer (CRC) and the correlation between its expression and prognosis.Methods
The expressions of miR-33b between CRC tissues and normal tissues were measured by real-time PCR. The effects of miR-33b on cell proliferation and cell cycle progression were detected by MTT assay, colony formation assay and flow cytometry. The potential regulations of miR-33b on multiple genes expression were verified by Western blot. Furthermore, the association of miR-33b with CRC clinicopathologic features and prognosis was analyzed by Chi-squared test and Kaplan–Meier tests.Results
MiR-33b was downregulated in CRC compared with normal colorectal samples and miR-33b inhibited tumor cell growth and induced cell cycle arrest. Western blot assays and correlation analysis showed that miR-33b could regulate multiple growth-related genes. Moreover, the expression of miR-33b was associated with TNM stage and tumor size, and CRC patients with high miR-33b expression had a better prognosis.Conclusion
Our data suggest that miR-33b functions as a tumor suppressor gene in CRC through regulating cell proliferation and cell cycle.3.
Bing Liu Shimeng Pan Yang Xiao Qianqian Liu Jingchao Xu Li Jia 《Journal of experimental & clinical cancer research : CR》2018,37(1):316
Background
Long non-coding RNAs (LncRNAs) emerging as pivotal marker in the procession of cancer, including colorectal cancer (CRC). Abnormal O-glycosylation is a crucial modification during cancer malignancy. The aim of this work is to analyze the alteration of O-glycosylation involved in CRC progression.Methods
qRT-PCR is utilized to screen the differential linc01296 expression in CRC tissues and cell lines. Functionally, CRC cell proliferation, aggressiveness and apoptosis are measured through relevant experiments, including CCK8 assay, colony formation assay, transwell assay, western blot and flow cytometry. Dual-luciferase reporter gene assay and RIP assay confirm the direct interaction between linc01296 and miR-26a. The xenografts and liver metatstatic nude mice models are established to show the inner effect of linc01296.Results
Differential expression of linc01296 is confirmed and closely correlated with the malignancy of CRC cell lines and poor clinical prognosis. Moreover, alteration of linc01296 affects CRC cell proliferation, metastasis and chemoresistance to 5-fluorouracil (5-FU) in vitro. Mechanically, linc01296 acts as a direct target of miR-26a, and thereby influenced CRC malignancy. Our investigation corroborates that linc01296 functions as an endogenous sponge of miR-26a to regulate mucin1 (MUC1) expression, catalyzed by GALNT3, which modulates the activity of PI3K/AKT pathway. Interestingly, upregulated linc01296 promotes the tumorigensis, liver metastasis and chemoresistance of CRC cell lines in vivo.Conclusion
These new findings indicate that linc01296/miR-26a/GALNT3 axis involves in the progression of CRC cells, illuminating the possible mechanism mediated by O-glycosylated MUC1 via PI3K/AKT pathway. This work renders potential diagnostic biomarkers and prospective therapeutic targets for CRC.4.
Wenpeng Zhang Tao Zhang Runsen Jin Hongchao Zhao Jin Hu Bo Feng Lu Zang Minhua Zheng Mingliang Wang 《Journal of experimental & clinical cancer research : CR》2014,33(1):113
Background
MicroRNAs (miRNAs) have been reported to play crucial roles in regulating a variety of genes pivotal for tumor metastasis. MicroRNA-301a (miR-301a) is overexpressed and displays oncogenic activity in many cancers. However, little is known about the potential roles of miR-301a in colorectal cancer (CRC).Methods
Taqman probe stem-loop real-time PCR was used to quantitatively measure the expression level of miR-301a in 48 cases of CRC tissues and the matched adjacent non-tumor mucosa as well as in CRC cell lines. miR-301a mimics and inhibitors were used to up-regulate and down-regulate miR-301a in CRC cells, respectively; lentivirus was used to construct miR-301a stably up- and down-regulated CRC cell lines. Metastasis ability was evaluated by transwell and wound healing assays while invasion was measured by transwell coated with matrix gel in vitro; in vivo metastasis was performed on nude mice model. The target of miR-301a was predicted by TargetScan software and validated by qRT-PCR, immunohistochemistry, western blot and luciferase reporter gene assay.Results
The expression of miR-301a was significantly higher in lymph node metastasis positive CRC samples compared with negative ones. Downregulation of miR-301a significantly inhibited the migration and invasion both in vitro and in vivo while forced up-regulation of miR-301a promoted migration and invasion. TGFBR2 was identified to be the downstream target of miR-301a. Knockdown of TGFBR2 in cells treated by miR-301a inhibitor elevated the previously abrogated migration and invasion.Conclusions
Our data indicated that miR-301a correlated with the metastatic and invasive ability in human colorectal cancers and miR-301a exerted its role as oncogene by targeting TGFBR2.5.
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H. G. Zhang X. W. Xu X. P. Shi B. W. Han Z. H. Li W. H. Ren P. J. Chen Y. F. Lou B. Li X. Y. Luo 《Clinical & translational oncology》2016,18(5):527-532
Background
The forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. The aim of this study was to evaluate the role of FOXM1 in CRC tumorigenesis.Methods
We investigated FOXM1 expression in 103 cases of primary CRC and matched normal tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on CRC proliferation and metastasis using in vitro models of CRC.Results
The results showed that high expression of FOXM1 staining was 85.44 % (88/103) in 103 cases of CRC and 20.39 % (21/103) in 103 cases of adjacent non-cancerous tissue samples; the difference of FOXM1 expression between two groups was statistically significant (P < 0.001). Silencing of FOXM1 inhibited the proliferation of CRC cells, and the invasion and migration of CRC cells were distinctly suppressed. Furthermore, FOXM1 knockdown led to substantial reductions in VEGF-A levels in CRC cell lines.Conclusions
Our data suggest that the pathogenesis of CRC maybe mediated by FOXM1, and FOXM1 could represent selective targets for the molecularly targeted treatments of CRC.9.
Philip Emmerich Linda Clipson Dustin A. Deming 《Current colorectal cancer reports》2017,13(4):334-340
Purpose of Review
Colorectal cancer (CRC) is a leading cause of cancer-related death and additional treatment options are urgently needed. Cytotoxic chemotherapy has been the mainstay of treatment options for patients for many years, including FOLFOX (leucovorin, 5-fluorouracil (5-FU), and oxaliplatin) or FOLFIRI (5-FU, leucovorin, and irinotecan) Here we review the current clinical use of systemic therapies for metastatic CRC and mechanisms of resistance to these agents.Recent Findings
Biologic therapies, including anti-angiogenic and anti-epidermal growth factor monoclonal antibodies, have shown increased efficacy for patients with metastatic CRC. Most recently, immunotherapies have also been an option for some patients.Summary
Identification of molecular markers predictive of response or resistance has led to enhanced ability to treat patients with metastatic CRC in a more personalized fashion.10.
Background
The neuronal guidance molecule Slit2 plays suppressive role in tumorigenesis and progression. We previously showed that Slit2-Robo1 inhibit cell migration in colorectal cancer (CRC). However, little is known about its downstream effectors in CRC. This study tries to identify whether the Slit-Robo Rho GTPase activating protein 1 (srGAP1) could mediate the inhibitory effect of Slit2-Robo1 on CRC cell migration.Methods
The protein expression of srGAP1 in clinical CRC tissues was tested by immunohistochemistry staining. Conditioned medium was prepared from HEK293 cells stably expressing Slit2-myc, Robo1-HA or RoboN (a soluble extracellular domain of Robo1). Immunoprecipitation (IP) was applied to check the interaction between Robo1 and srGAP1, and immunofluorescence (IF) was used to observe the subcellular localization of Robo1 and srGAP1. Small GTPase pull-down assay was used to determine the activity of Cdc42. A modified wound healing assay was performed to detect cell migration.Results
The protein expression of srGAP1 was remarkably decreased in 47.5% of CRC tissues compared with adjacent noncancerous tissues, and the decreased srGAP1 expression was associated with lymphatic invasion, poor tumor differentiation, high TNM stage, and poor survival (P?<?0.05). IP and IF assays revealed that srGAP1 was a Robo1-interacting protein and exhibited similar dynamic subcellular distribution after Slit2 treatment in CRC cells. Small GTPase pull-down assay and migration assay indicated that Slit2-Robo1 signaling inhibited Cdc42 activity and CRC cell motility through srGAP1.Conclusion
Downregulation of srGAP1 in CRC was associated with tumor progression and poor prognosis. srGAP1 is an important downstream molecule of Slit2 signalling in CRC, and mediates the anti-migration function of Slit2 by inhibiting Cdc42.11.
Background
Colorectal cancer (CRC) is the third leading cause of cancer deaths worldwide. In recent years overall survival, particularly in the metastatic setting, could be substantially prolonged. This is not least due to novel options for systemic treatment of metastatic CRC (mCRC). A major contribution to this development came from the increasing understanding of genetic and epigenetic dysregulation in CRC that lead to dysregulated signaling networks in tumors and subsequently to dysregulated cell survival, tumor growth and metastasis. Various strategies have been developed to selectively disrupt vital signaling networks of tumors and novel targeted drugs have a major effect on the tumor and (ideally) only minimal adverse drug reactions (targeted therapies).Aim
This article gives an overview on established and new treatment options for mCRC and discusses novel study results and therapeutic concepts. There is an increasing number of clearly defined molecular therapeutic concepts that show impressive results (e.g. for BRAF mutant tumors, HER2 amplified tumors or mismatch repair deficient tumors) albeit only for small subgroups of patients.12.
Purpose of Review
To introduce recent progress on circulating tumor cell (CTC) research in colorectal cancer (CRC) and to highlight clinical application of CTCs from detection to assessment of treatment response.Recent Findings
CTC biological characteristics in CRC play an important role in the detection of CTCs. The in vitro culture of CTCs from CRC patients (cell lines and organoids) can potentially facilitate rapid drug testing and treatment prediction. CTC detection should be standardized with improved detection rate in CRC; further, clinical investigation is still needed to clarify its potential as a tool for early CRC detection, a predictive and prognostic marker to ultimately guide treatment.Summary
Gaining an improved understanding of CTCs characteristics and ultimately, integration of CTC detection and utilization of CTCs may lead to optimized tumor treatment and facilitate precision medicine.13.
Apple G. Long Emma T. Lundsmith Kathryn E. Hamilton 《Current colorectal cancer reports》2017,13(4):341-351
Purpose of Review
Colorectal cancer (CRC) is the fourth most common cancer in both men and women in the USA, resulting in over 55,000 deaths annually. Environmental and genetic factors influence the development of CRC, and inflammation is a critical hallmark of cancer that may arise from a variety of factors. While patients with inflammatory bowel disease (IBD) have a higher risk of developing CRC, sporadic CRCs may engender or be potentiated by inflammation as well. In this review, we focus on recent advances in basic and translational research utilizing murine models to understand the contribution of inflammatory signaling pathways to CRC.Recent Findings
We discuss advances in the utility of three-dimensional enteroid/colonoid/tumoroid cultures to understand immune-epithelial interactions in CRC, as well as the potential for utilizing patient-derived tumoroids for personalized therapies.Summary
This review underscores the importance of understanding the complex molecular mechanisms underlying inflammation in sporadic CRC and highlights up-and-coming or new avenues for CRC biomarkers or therapies.14.
Purpose of Review
This review will discuss the impact of patient age and comorbidity on colorectal cancer (CRC) screening value.Recent Findings
Society guidelines recommend CRC screening starting at age 50 in average-risk individuals, but there is less agreement about when screening should be discontinued. In clinical practice, CRC screening and follow-up recommendations among elderly patients appear to be driven more by chronological age than by comorbid illnesses. However, several studies have highlighted the interaction between age and comorbidity burden when selecting appropriate patients for CRC screening. Although CRC screening may be beneficial until age 75–80 years among patients with no comorbidity, it has only modest benefits at an early age in those with high comorbidity.Summary
Clinicians should adopt the concept of “health-adjusted age” and identify “healthy elderly” patients who would benefit from CRC screening and the “unhealthy young” in whom the benefits of CRC screening are likely limited.15.
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Sarah Moreland-Russell Prajakta Adsul Seif Nasir Maria E. Fernandez Timothy J. Walker Heather M. Brandt Robin C. Vanderpool Meagan Pilar Paula Cuccaro Wynne E. Norton Cynthia A. Vinson David A. Chambers Ross C. Brownson 《Cancer causes & control : CCC》2018,29(12):1221-1230
Purpose
In 2015–2016, the Comprehensive Cancer Control National Partnership provided technical assistance workshops to support 22 cancer coalitions in increasing human papillomavirus (HPV) vaccination uptake and increasing colorectal cancer (CRC) screening in their local communities. As national efforts continue to invest in providing technical assistance, there is a current gap in understanding its use as a strategy to accelerate implementation of evidence-based interventions (EBIs) for cancer prevention. The objective of this study was to evaluate the impact of technical assistance on the participants’ knowledge, attitudes, and skills for implementing EBIs in their local context and enhancing state team collaboration.Methods
Data were collected August-November 2017 using web-based questionnaires from 44 HPV workshop participants and 66 CRC workshop participants.Results
Both HPV vaccination and CRC screening workshop participants reported changes in knowledge, attitudes, and skills related to implementing EBIs in their local state context. Several participants reported increased abilities in communicating and coordinating with partners in their states and utilizing additional implementation strategies to increase HPV vaccination uptake and CRC screening rates.Conclusions
Findings from this study suggest that providing technical assistance to members of comprehensive cancer control coalitions is useful in promoting collaborations and building capacity for implementing EBIs for cancer prevention and control.18.
Xihui Wang Rui Yang Chunyan Yuan Yanli An Qiusha Tang Daozhen Chen 《Targeted oncology》2018,13(4):481-494
Background
Ovarian cancer is a common gynecologic malignancy with poor prognosis, requiring innovative new therapeutic strategies. Temperature-controlled drug delivery to cancer cells represents a novel, promising, targeted treatment approach.Objective
We prepared folate receptor-targeted thermosensitive liposomes wrapped with the HSP90 inhibitor 17-AAG and superparamagnetic material (17-AAG/MTSLs-FA), and tested the efficacy of these targeted magnetoliposomes in vitro and in vivo.Methods
Magnetic thermosensitive liposomes wrapped with 17-AAG were coprecipitated with Fe3O4 magnetic nanoparticles and prepared by a rotary evaporation method. Experiments were conducted with SKOV3 human ovarian cancer cells and MCF7 human breast carcinoma cells to evaluate the anti-tumor effects.Results
17-AAG/MTSLs-FA prepared in this study met the basic requirements for therapeutic application. The preparation method is relatively simple and the raw materials are readily available. The product exhibited strong magnetism, high encapsulation efficiencies, and satisfactory performance. The liposomes combined with hyperthermia significantly inhibited the proliferation of SKOV3 cells and induced apoptosis. Experiments using a mouse subcutaneous model as well as an ascites tumor xenograft model indicated that 17-AAG/MTSLs-FA was stable in vivo and effectively targeted tumor tissues expressing the folate receptor.Conclusions
Folic acid-conjugated 17-AAG magnetic thermosensitive liposomes in combination with an alternating magnetic field for heating can achieve a synergistic anti-tumor effect of chemotherapy and heat treatment, potentially offering a new method for ovarian cancer treatment.19.
Sandra Garcia Sandi L. Pruitt Amit G. Singal Caitlin C. Murphy 《Cancer causes & control : CCC》2018,29(11):1039-1046
Purpose
Colorectal cancer (CRC) incidence has declined over the past two decades; however, these declines have not occurred equally in all populations. To better understand the impact of CRC among Hispanics, we examined incidence trends by age and Hispanic ethnicity.Methods
Using data from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results Program, we estimated CRC incidence rates during the period 2001–2014, and across all 50 U.S. states. We estimated incidence rates in younger (age?<?50 years) and older (age?≥?50 years) adults by anatomic subsite and stage at diagnosis, separately for non-Hispanic Whites and Hispanic Whites.Results
CRC incidence rates declined among older (age?≥?50 years) Whites and Hispanics, but Whites experienced a greater decline (31% vs. 27% relative decline among Hispanics). In contrast to older adults, there were continued increases in CRC incidence from 2001 to 2014 among younger (age 20–49 years) adults. The largest relative increases in incidence occurred in Hispanics aged 20–29 years (90% vs. 50% relative increase among Whites).Conclusions
Opposing incidence trends in younger versus older Hispanics may reflect generational differences in CRC risk by birth cohort, as well as environmental exposures and lifestyle-related risk factors associated with immigration and acculturation.20.