Publications by authors named "Yitian Xu"

16 Publications

  • Page 1 of 1

A safe feature elimination rule for L1-regularized logistic regression.

IEEE Trans Pattern Anal Mach Intell 2021 Apr 6;PP. Epub 2021 Apr 6.

The L1-regularized logistic regression (L1-LR) is popular for classification problems. To accelerate its training speed for high-dimensional data, techniques named safe screening rules have been proposed recently. They can safely delete the inactive features in data so as to greatly reduce the training cost of L1-LR. The screening power of these rules is determined by their corresponding safe regions, which is also the core technique of safe screening rules. In this paper, we introduce a new safe feature elimination rule (SFER) for L1-LR. Compared to existing safe rules, the safe region of SFER is improved in two aspects: (1) a smaller sphere region is constructed by using the strong convexity of dual L1-LR twice; (2) multiple half-spaces, which correspond to the potential active constraints, are added for further contraction. Both improvements can enhance the screening ability of SFER. As for the complexity of SFER, an iterative filtering framework is given by decomposing the safe region into multiple ``domes". In this way, SFER admits a closed form solution and the identified features will not be scanned repeatedly. Experiments on ten benchmark data sets demonstrate that SFER gives superior performance than existing methods on training efficiency.
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http://dx.doi.org/10.1109/TPAMI.2021.3071138DOI Listing
April 2021

Catechol Dyes-Tyrosinase System for Colorimetric Determination and Discrimination of Dithiocarbamate Pesticides.

J Agric Food Chem 2020 Aug 12;68(34):9252-9259. Epub 2020 Aug 12.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Science, China Agricultural University, Beijing 100193, China.

A convenient and straightforward method, which is based on catechol dyes and tyrosinase, for colorimetric determination and discrimination of dithiocarbamate pesticides (DTCs) has been fabricated. Three catechol dyes, including pyrocatechol violet (PV), pyrogallol red (PR), and bromopyrogallol red (BPR), were chosen as both substrates and indicators in this method. Tyrosinase can facilitate oxidation of the catechol dyes, altering color and absorbance spectra of the dyes. DTCs can alter the absorbance spectra of the catechol dyes-tyrosinase system due to their inhibitory effects on tyrosinase. As a result, the detection limit of the PV-tyrosinase system on ziram was determined to be 4.5 μg L. By implementing PV-tyrosinase, PR-tyrosinase, and BPR-tyrosinase, the colorimetric array successfully distinguished six DTCs (thiram, ziram, diram, ferbam, metiram, and mancozeb) at 5.0 μM using principal component analysis (PCA). The system can also determine ziram and distinguish DTCs in real samples. Furthermore, a smartphone can be used as a detector in this system to improve its real-world applications.
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http://dx.doi.org/10.1021/acs.jafc.0c03352DOI Listing
August 2020

Potentiating Antitumor Efficacy Through Radiation and Sustained Intratumoral Delivery of Anti-CD40 and Anti-PDL1.

Int J Radiat Oncol Biol Phys 2021 Jun 5;110(2):492-506. Epub 2020 Aug 5.

Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas; Department of Radiation Oncology, Houston Methodist Research Institute, Houston, Texas; Department of Surgery, Houston Methodist Research Institute, Houston, Texas. Electronic address:

Purpose: Mounting evidence demonstrates that combining radiation therapy (RT) with immunotherapy can reduce tumor burden in a subset of patients. However, conventional systemic delivery of immunotherapeutics is often associated with significant adverse effects, which force treatment cessation. The aim of this study was to investigate a minimally invasive therapeutics delivery approach to improve clinical response while attenuating toxicity.

Methods And Materials: We used a nanofluidic drug-eluting seed (NDES) for sustained intratumoral delivery of combinational antibodies CD40 and PDL1. To enhance immune and tumor response, we combined the NDES intratumoral platform with RT to treat the 4T1 murine model of advanced triple negative breast cancer. We compared the efficacy of NDES against intraperitoneal administration, which mimics conventional systemic treatment. Tumor growth was recorded, and local and systemic immune responses were assessed via imaging mass cytometry and flow cytometry. Livers and lungs were histologically analyzed for evaluation of toxicity and metastasis, respectively.

Results: The combination of RT and sustained intratumoral immunotherapy delivery of CD40 and PDL1 via NDES (NDES CD40/PDL1) showed an increase in both local and systemic immune response. In combination with RT, NDES CD40/PDL1 achieved significant tumor burden reduction and liver inflammation mitigation compared with systemic treatment. Importantly, our treatment strategy boosted the abscopal effect toward attenuating lung metastatic burden.

Conclusions: Overall, our study demonstrated superior efficacy of combination treatment with RT and sustained intratumoral immunotherapy via NDES, offering promise for improving therapeutic index and clinical response.
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http://dx.doi.org/10.1016/j.ijrobp.2020.07.2326DOI Listing
June 2021

The ELF3-PIF7 Interaction Mediates the Circadian Gating of the Shade Response in Arabidopsis.

iScience 2019 Dec 20;22:288-298. Epub 2019 Nov 20.

State Key Laboratory of Genetic Engineering and Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200438, People's Republic of China. Electronic address:

Light filtered through dense planting initiates the shade avoidance syndrome (SAS) in plants, which helps them compete against their neighbors. Quantitative trait loci (QTL)-based analysis identified the nighttime-expressed clock component ELF3 as a new player in the SAS, but its detailed mechanism is unclear. Here, we show that the circadian clock gates shade-induced gene expression and hypocotyl elongation at night. ELF3 is involved in nighttime suppression via interaction with and inactivation of PHYTOCHROME-INTERACTING FACTOR 7 (PIF7). Loss of function of ELF3 restores the shade induction, which is largely reduced in the absence of PIF7, indicating that ELF3 acts upstream of PIF7. Finally, we found that the repressive activity of ELF3 on the shade response is stronger under short days than under long days. Our results reveal that the interaction between ELF3 and PIF7 mediates the circadian gating of the SAS, which coordinates the daily control of physiological outputs.
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http://dx.doi.org/10.1016/j.isci.2019.11.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909221PMC
December 2019

Overexpression of Hsc70 promotes proliferation, migration, and invasion of human glioma cells.

J Cell Biochem 2019 06 28;120(6):10707-10714. Epub 2019 Feb 28.

Department of Neurosurgery, Yancheng Third People's Hospital, Yancheng, P. R. China.

Migration and invasion are often recognized as the main reasons for the high recurrence and death rates of glioma and limit the efficacy of surgery and other antitumor therapies. In this study, we found over activation of heat shock cognate protein 70 (Hsc70) in human glioma specimens, which was closely related to glioma grade. We investigated whether Hsc70 induced the migration and invasion of glioma cells. Wound healing and transwell migration assay were used to determine the migration and invasion ability of human glioma U251 and U87 cells, in which the expression of Hsc70 was knocked down by small interfering RNA. Western blot analysis was performed to determine the expression of FAK-Src signaling in malignant glioma cells. The results showed that Hsc70 deficiency significantly retarded migration and invasion and reduced the phosphorylation of FAK, Src, and Pyk2 in U251 and U87 cells. Overall, our results indicate that the migration and invasion capacity of human brain glioma cells is at least partly induced by Hsc70-dependent activation of FAK-Src signaling.
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http://dx.doi.org/10.1002/jcb.28362DOI Listing
June 2019

Exploitation of Synthetic mRNA To Drive Immune Effector Cell Recruitment and Functional Reprogramming In Vivo.

J Immunol 2019 01 12;202(2):608-617. Epub 2018 Dec 12.

Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853;

Therapeutic strategies based on in vitro-transcribed mRNA (IVT) are attractive because they avoid the permanent signature of genomic integration that is associated with DNA-based therapy and result in the transient production of proteins of interest. To date, IVT has mainly been used in vaccination protocols to generate immune responses to foreign Ags. In this "proof-of-principle" study, we explore a strategy of combinatorial IVT to recruit and reprogram immune effector cells to acquire divergent biological functions in mice in vivo. First, we demonstrate that synthetic mRNA encoding CCL3 is able to recruit murine monocytes in a nonprogrammed state, exhibiting neither bactericidal nor tissue-repairing properties. However, upon addition of either mRNA or mRNA, we successfully polarized these cells to adopt either M1 or M2 macrophage activation phenotypes. This cellular reprogramming was demonstrated through increased expression of known surface markers and through the differential modulation of NADPH oxidase activity, or the superoxide burst. Our study demonstrates how IVT strategies can be combined to recruit and reprogram immune effector cells that have the capacity to fulfill complex biological tasks in vivo.
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http://dx.doi.org/10.4049/jimmunol.1800924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325005PMC
January 2019

A Novel and Safe Two-Stage Screening Method for Support Vector Machine.

IEEE Trans Neural Netw Learn Syst 2019 08 3;30(8):2263-2274. Epub 2018 Dec 3.

To make support vector machine (SVM) applicable to large-scale data sets, safe screening rules are developed recently. The main idea is to reduce the scale of SVM by safely discarding the redundant training samples. Among existing safe screening rules, the dual screening method with variational inequalities (DVI) and the dynamic screening rule (DSR) based on duality gap are two representative strategies. DVI is efficient, while its safety may be affected by inaccurate solving algorithms. DSR is guaranteed to be safe; however, accurate feasible solutions are required for good efficiency. Based on the above-mentioned studies, in this paper, a two-stage screening (TSS) rule, which fully exploits the advantages of the above-mentioned two approaches and improves their shortcomings, is proposed. First, DVI is applied prior to training for sample screening. It reduces the scale of SVM and, meanwhile, produces a better initial feasible solution for DSR. Then, by embedding DSR into the solving algorithm, the solver becomes more accurate, and the safety of DVI can be strengthened. In the end, for safety guarantee, a postchecking step is added to search the wrongly identified samples and retrain them. To theoretically analyze the safety of DVI, an upper bound of the deviation in DVI is estimated, and a Safe-DVI is given based on it. To ensure the efficiency of TSS, the superiority of DVI over initial DSR is verified. In addition, kernel version of TSS is also given for nonlinear SVM. Numerical experiments on synthetic data sets and 12 real-world data sets verify the efficiency and safety of this TSS.
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http://dx.doi.org/10.1109/TNNLS.2018.2879800DOI Listing
August 2019

Enhanced Permeability and Retention-like Extravasation of Nanoparticles from the Vasculature into Tuberculosis Granulomas in Zebrafish and Mouse Models.

ACS Nano 2018 08 15;12(8):8646-8661. Epub 2018 Aug 15.

Department of Biosciences , University of Oslo , Blindernveien 31 , 0371 Oslo , Norway.

The enhanced permeability and retention (EPR) effect is the only described mechanism enabling nanoparticles (NPs) flowing in blood to reach tumors by a passive targeting mechanism. Here, using the transparent zebrafish model infected with Mycobacterium marinum we show that an EPR-like process also occurs allowing different types of NPs to extravasate from the vasculature to reach granulomas that assemble during tuberculosis (TB) infection. PEGylated liposomes and other NP types cross endothelial barriers near infection sites within minutes after injection and accumulate close to granulomas. Although ∼100 and 190 nm NPs concentrated most in granulomas, even ∼700 nm liposomes reached these infection sites in significant numbers. We show by confocal microscopy that NPs can concentrate in small aggregates in foci on the luminal side of the endothelium adjacent to the granulomas. These spots are connected to larger foci of NPs on the ablumenal side of these blood vessels. EM analysis suggests that NPs cross the endothelium via the paracellular route. PEGylated NPs also accumulated efficiently in granulomas in a mouse model of TB infection with Mycobacterium tuberculosis, arguing that the zebrafish embryo model can be used to predict NP behavior in mammalian hosts. In earlier studies we and others showed that uptake of NPs by macrophages that are attracted to infection foci is one pathway for NPs to reach TB granulomas. This study reveals that when NPs are designed to avoid macrophage uptake, they can also efficiently target granulomas via an alternative mechanism that resembles EPR.
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http://dx.doi.org/10.1021/acsnano.8b04433DOI Listing
August 2018

Neuroprotective effects of metformin on traumatic brain injury in rats associated with NF-κB and MAPK signaling pathway.

Brain Res Bull 2018 06 24;140:154-161. Epub 2018 Apr 24.

Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Traumatic brain injury (TBI) triggers a complex sequence of inflammatory responses that contribute to secondary injury. Metformin, a first-line drug used to treat type 2 diabetes, is reported to exhibit potent anti-inflammatory activity on diseases associated with the central nervous system (CNS). The aim of this study is to investigate the potential neuroprotective effects of metformin on acute brain injury after TBI and explore the underlying mechanisms. Male Sprague-Dawley (SD) rats were divided into four groups: sham group, TBI group, TBI + saline (NS) group and TBI + metformin group. A weight-dropping model was employed to induce TBI in rats. Modified neurological severity scores (mNSS) were employed to assess the short-term neurological deficits, neuronal degeneration and apoptosis in the brain tissues were assayed with Fluoro-Jade B and TUNEL staining, immunofluorescence was designed to investigate microglial activation. The mRNA and protein expression levels of pro-inflammatory cytokines such as necrosis factor-alpha (TNF-α), interleukin-beta (IL-1β) and nterleukin-6 (IL-6) were evaluated by real-time quantitative reverse transcriptase polymerase chain reaction (QPCR) and enzyme-linked immunosorbent assay (ELISA). Western blotting analysis was engaged to examine the expression of NF-κB p65 and phosphorylation of ERK1/2 and p38 MAPK. Our results showed that metformin significantly ameliorated neurological deficit, cerebral edema and neuronal apoptosis in rats following TBI. Moreover, metformin administration inhibited microglial activation and decreased the production of pro-inflammatory cytokines including TNF-α, IL-1β and IL-6. In addition, metformin inhibited the translocation of NF-κB p65 from cytoplasm into the nucleus, as well as the phosphorylation of ERK1/2 and p38 MAPK. This study suggests that metformin administration inhibits microglia activation-mediated inflammation via NF-κB and MAPK signaling pathway to improve neurobehavioral function following TBI, which provide a potential therapeutic benefit in treating brain injury.
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http://dx.doi.org/10.1016/j.brainresbull.2018.04.008DOI Listing
June 2018

Matrix metalloproteinase inhibitors enhance the efficacy of frontline drugs against Mycobacterium tuberculosis.

PLoS Pathog 2018 04 26;14(4):e1006974. Epub 2018 Apr 26.

Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, United States of America.

Mycobacterium tuberculosis (Mtb) remains a grave threat to world health with emerging drug resistant strains. One prominent feature of Mtb infection is the extensive reprogramming of host tissue at the site of infection. Here we report that inhibition of matrix metalloproteinase (MMP) activity by a panel of small molecule inhibitors enhances the in vivo potency of the frontline TB drugs isoniazid (INH) and rifampicin (RIF). Inhibition of MMP activity leads to an increase in pericyte-covered blood vessel numbers and appears to stabilize the integrity of the infected lung tissue. In treated mice, we observe an increased delivery and/or retention of frontline TB drugs in the infected lungs, resulting in enhanced drug efficacy. These findings indicate that targeting Mtb-induced host tissue remodeling can increase therapeutic efficacy and could enhance the effectiveness of current drug regimens.
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http://dx.doi.org/10.1371/journal.ppat.1006974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919409PMC
April 2018

RACK1 upregulation induces neuroprotection by activating the IRE1-XBP1 signaling pathway following traumatic brain injury in rats.

Exp Neurol 2018 06 6;304:102-113. Epub 2018 Mar 6.

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Receptor for activated protein kinase C 1 (RACK1) is a multifaceted scaffolding protein known to be involved in the regulation of signaling events required for neuronal protection. In the present study, we investigated the role of RACK1 in secondary brain injury in a rat traumatic brain injury (TBI) model. A weight-drop TBI model was established in Sprague Dawley rats, and RACK1 in vivo knockdown and overexpression were performed 24 h before TBI insult. The IRE1 inhibitor 3,5-dibromosalicylaldehyde (DBSA) was administered by intracerebroventricular injection 1 h after TBI insult. Real-time PCR, Western blotting, immunofluorescence, neuronal apoptosis, brain water content, and neurological scores were evaluated. Our results revealed that TBI induced increased expression of endogenous RACK1, phosphorylated inositol-requiring enzyme 1 (p-IRE1), X-box binding protein-1 (XBP1) and glucose-regulated protein 78 (GRP78) in neurons. RACK1 overexpression significantly ameliorated neuronal apoptosis, blood-brain barrier disruption, brain edema and neurological deficits at 48 h after TBI, which was concomitant with upregulation of p-IRE1, XBP1 and GRP78 expression, while its knockdown induced the opposite effects. Furthermore, DBSA administration reversed the protective effects of RACK1 overexpression against brain injury and decreased the expression of p-IRE1, XBP1 and GRP78. In summary, the upregulation of RACK1 following brain contusion exerted neuroprotective effects against secondary brain injury, which were probably mediated by activation of the IRE1-XBP1 pathway.
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http://dx.doi.org/10.1016/j.expneurol.2018.03.003DOI Listing
June 2018

Safe Screening Rules for Accelerating Twin Support Vector Machine Classification.

IEEE Trans Neural Netw Learn Syst 2018 05 11;29(5):1876-1887. Epub 2017 Apr 11.

The twin support vector machine (TSVM) is widely used in classification problems, but it is not efficient enough for large-scale data sets. Furthermore, to get the optimal parameter, the exhaustive grid search method is applied to TSVM. It is very time-consuming, especially for multiparameter models. Although many techniques have been presented to solve these problems, all of them always affect the performance of TSVM to some extent. In this paper, we propose a safe screening rule (SSR) for linear-TSVM, and give a modified SSR (MSSR) for nonlinear TSVM, which contains multiple parameters. The SSR and MSSR can delete most training samples and reduce the scale of TSVM before solving it. Sequential versions of SSR and MSSR are further introduced to substantially accelerate the whole parameter tuning process. One important advantage of SSR and MSSR is that they are safe, i.e., we can obtain the same solution as the original problem by utilizing them. Experiments on eight real-world data sets and an imbalanced data set with different imbalanced ratios demonstrate the efficiency and safety of SSR and MSSR.
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http://dx.doi.org/10.1109/TNNLS.2017.2688182DOI Listing
May 2018

Maximum Margin of Twin Spheres Support Vector Machine for Imbalanced Data Classification.

Authors:
Yitian Xu

IEEE Trans Cybern 2017 Jun 21;47(6):1540-1550. Epub 2016 Apr 21.

Twin support vector machine (TSVM) finds two nonparallel planes by solving a pair of smaller-sized quadratic programming problems (QPPs) rather than a single large one as in the conventional support vector machine (SVM); this makes the learning speed of TSVM approximately four times faster than that of the standard SVM. One major limitation of TSVM is that it involves an expensive matrix inverse operation when solving the dual problem. In addition, TSVM is less effective when dealing with the imbalanced data. In this paper, we propose a maximum margin of twin spheres support vector machine (MMTSSVM) for imbalanced data classification. MMTSSVM only needs to find two homocentric spheres. On one hand, the small sphere captures as many samples in the majority class as possible; on the other hand, the large sphere pushes out most samples in the minority class by increasing the margin between two homocentric spheres. MMTSSVM involves a QPP and a linear programming problem as opposed to a pair of QPPs as in classical TSVM or a larger-sized QPP in SVM, thus it greatly increases the computational speed. More importantly, MMTSSVM avoids the matrix inverse operation. The property of parameters in MMTSSVM is discussed and testified by one artificial experiment. Experimental results on nine benchmark datasets demonstrate the effectiveness of the proposed MMTSSVM in comparison with state-of-the-art algorithms. Finally, we apply MMTSSVM into Alzheimer's disease medical experiment and also obtain a better experimental result.
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http://dx.doi.org/10.1109/TCYB.2016.2551735DOI Listing
June 2017

A Novel Twin Support-Vector Machine With Pinball Loss.

IEEE Trans Neural Netw Learn Syst 2017 02 13;28(2):359-370. Epub 2016 Jan 13.

Twin support-vector machine (TSVM), which generates two nonparallel hyperplanes by solving a pair of smaller-sized quadratic programming problems (QPPs) instead of a single larger-sized QPP, works faster than the standard SVM, especially for the large-scale data sets. However, the traditional TSVM adopts hinge loss which easily leads to its sensitivity of the noise and instability for resampling. To enhance the performance of the TSVM, we present a novel TSVM with the pinball loss (Pin-TSVM) which deals with the quantile distance and is less sensitive to noise points. We further investigate its properties, including the noise insensitivity, between-class distance maximization, and within-class scatter minimization. In addition, we compare our Pin-TSVM with the twin parametric-margin SVM and the SVM with the pinball loss in theory. Numerical experiments on a synthetic data set and 14 benchmark data sets with different noises demonstrate the feasibility and validity of our proposed method.
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http://dx.doi.org/10.1109/TNNLS.2015.2513006DOI Listing
February 2017

Comprehensive models of human primary and metastatic colorectal tumors in immunodeficient and immunocompetent mice by chemokine targeting.

Nat Biotechnol 2015 Jun 25;33(6):656-60. Epub 2015 May 25.

Department of Medicine, Weill Cornell Medical College, New York, New York, USA.

Current orthotopic xenograft models of human colorectal cancer (CRC) require surgery and do not robustly form metastases in the liver, the most common site clinically. CCR9 traffics lymphocytes to intestine and colorectum. We engineered use of the chemokine receptor CCR9 in CRC cell lines and patient-derived cells to create primary gastrointestinal (GI) tumors in immunodeficient mice by tail-vein injection rather than surgery. The tumors metastasize inducibly and robustly to the liver. Metastases have higher DKK4 and NOTCH signaling levels and are more chemoresistant than paired subcutaneous xenografts. Using this approach, we generated 17 chemokine-targeted mouse models (CTMMs) that recapitulate the majority of common human somatic CRC mutations. We also show that primary tumors can be modeled in immunocompetent mice by microinjecting CCR9-expressing cancer cell lines into early-stage mouse blastocysts, which induces central immune tolerance. We expect that CTMMs will facilitate investigation of the biology of CRC metastasis and drug screening.
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http://dx.doi.org/10.1038/nbt.3239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532544PMC
June 2015

miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β.

Nat Commun 2015 Apr 15;6:6879. Epub 2015 Apr 15.

1] School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA [2] Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA [3] Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.

As patient survival drops precipitously from early-stage cancers to late-stage and metastatic cancers, microRNAs that promote relapse and metastasis can serve as prognostic and predictive markers as well as therapeutic targets for chemoprevention. Here we show that miR-1269a promotes colorectal cancer (CRC) metastasis and forms a positive feedback loop with TGF-β signalling. miR-1269a is upregulated in late-stage CRCs, and long-term monitoring of 100 stage II CRC patients revealed that miR-1269a expression in their surgically removed primary tumours is strongly associated with risk of CRC relapse and metastasis. Consistent with clinical observations, miR-1269a significantly increases the ability of CRC cells to invade and metastasize in vivo. TGF-β activates miR-1269 via Sox4, while miR-1269a enhances TGF-β signalling by targeting Smad7 and HOXD10, hence forming a positive feedback loop. Our findings suggest that miR-1269a is a potential marker to inform adjuvant chemotherapy decisions for CRC patients and a potential therapeutic target to deter metastasis.
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http://dx.doi.org/10.1038/ncomms7879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399006PMC
April 2015