Publications by authors named "Jianyang Hu"

16 Publications

  • Page 1 of 1

Nitazoxanide impairs mitophagy flux through ROS-mediated mitophagy initiation and lysosomal dysfunction in bladder cancer.

Biochem Pharmacol 2021 May 4;190:114588. Epub 2021 May 4.

Institute of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China; Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen 518000, China; Teaching Center of Shenzhen Luohu Hospital, Shantou University Medical College, Shenzhen 518000, China; Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China. Electronic address:

Bladder cancer is one of the most common malignancy in the urinary tract with high recurrence and drug resistance in clinics. Alternative treatments from existing drugs might be a promising strategy. Nitazoxanide (NTZ), an FDA-approved antiprotozoal drug, has got increasingly noticed because of its favorable safety profile and antitumor potential, yet the effects in bladder cancer and underlying mechanisms remain poorly understood. Herein, we find that NTZ induces mitochondrial damage and mitophagy initiation through PINK1-generated phospho-ubiquitin(pS65-Ub) and autophagy receptor-mediated pathway even in the absence of Atg5/Beclin1. Meanwhile, NTZ inhibits lysosomal degradation activity, leading to mitophagy flux impairment at late stage. Mitochondrial reactive oxygen species (ROS) production is critical in this process, as eliminating ROS with N-acetylcysteine (NAC) efficiently inhibits PINK1 signaling-mediated mitophagy initiation and alleviates lysosomal dysfunction. Co-treatment with NTZ and autophagy inhibitor Chloroquine (CQ) to aggravate mitophagy flux impairment promotes NTZ-induced apoptosis, while alleviation of mitophagy flux impairment with ROS scavenger reduces cell death. Moreover, we also discover a similar signaling response in the 3D bladder tumor spheroid after NTZ exposure. In vivo study reveals a significant inhibition of orthotopic bladder tumors with no obvious systemic toxicity. Together, our results uncover the anti-tumor activities of NTZ with the involvement of ROS-mediated mitophagy modulation at different stages and demonstrate it as a potential drug candidate for fighting against bladder tumors.
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http://dx.doi.org/10.1016/j.bcp.2021.114588DOI Listing
May 2021

Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling.

Nat Commun 2021 04 14;12(1):2242. Epub 2021 Apr 14.

Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong.

Breast cancer is a heterogeneous disease, affecting over 3.5 million women worldwide, yet the functional role of cis-regulatory elements including super-enhancers in different breast cancer subtypes remains poorly characterized. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. Here we apply integrated epigenomic and transcriptomic profiling to uncover super-enhancer heterogeneity between breast cancer subtypes, and provide clinically relevant biological insights towards TNBC. Using CRISPR/Cas9-mediated gene editing, we identify genes that are specifically regulated by TNBC-specific super-enhancers, including FOXC1 and MET, thereby unveiling a mechanism for specific overexpression of the key oncogenes in TNBC. We also identify ANLN as a TNBC-specific gene regulated by super-enhancer. Our studies reveal a TNBC-specific epigenomic landscape, contributing to the dysregulated oncogene expression in breast tumorigenesis.
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http://dx.doi.org/10.1038/s41467-021-22445-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046763PMC
April 2021

Fiber micro-tip temperature sensor based on cholesteric liquid crystal.

Opt Lett 2020 Sep;45(18):5209-5212

This Letter proposes and demonstrates a novel, miniature fiber-tip temperature sensor with a tapered hollow capillary tube (HCT) filled with glycerin and dye-doped cholesteric liquid crystal (CLC). The function of glycerin is to provide a surface anchoring force to control the uniform orientation of CLC molecules, so that the CLC in the tapered HCT can be considered as a mirrorless photonic bandgap (PBG) microcavity. An unambiguously identifiable PBG mode single peak appears in the emission spectra of the sensor. The CLC-based fiber-tip temperature sensor has a temperature sensitivity of -9.167/, and the figure of merit can reach 67.4. This sensor offers key features and advantages, including compactness, unambiguous identifiability, and biocompatibility, which can satisfy requirements of temperature measurement in various temperature sensing application fields and has great potential for biochemical detection at cell level. In addition, the CLC was integrated into the optical fiber terminal, and the PBG mode is excited, collected and transmitted by the multimode fiber coupler, which is reported for the first time, to the best of our knowledge.
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http://dx.doi.org/10.1364/OL.402473DOI Listing
September 2020

Phase-separated condensate-aided enrichment of biomolecular interactions for high-throughput drug screening in test tubes.

J Biol Chem 2020 08 27;295(33):11420-11434. Epub 2020 May 27.

Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

Modification-dependent and -independent biomolecular interactions, including protein-protein, protein-DNA/RNA, protein-sugar, and protein-lipid interactions, play crucial roles in all cellular processes. Dysregulation of these biomolecular interactions or malfunction of the associated enzymes results in various diseases; therefore, these interactions and enzymes are attractive targets for therapies. High-throughput screening can greatly facilitate the discovery of drugs for these targets. Here, we describe a biomolecular interaction detection method, called phase-separated ondensate-aided nrichment of iomolecular nteractions in est tubes (CEBIT). The readout of CEBIT is the selective recruitment of biomolecules into phase-separated condensates harboring their cognate binding partners. We tailored CEBIT to detect various biomolecular interactions and activities of biomolecule-modifying enzymes. Using CEBIT-based high-throughput screening assays, we identified known inhibitors of the p53/MDM2 (MDM2) interaction and of the histone methyltransferase, suppressor of variegation 3-9 homolog 1 (SUV39H1), from a compound library. CEBIT is simple and versatile, and is likely to become a powerful tool for drug discovery and basic biomedical research.
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http://dx.doi.org/10.1074/jbc.RA120.012981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450138PMC
August 2020

Fiber Mach-Zehnder-interferometer-based liquid crystal biosensor for detecting enzymatic reactions of penicillinase.

Appl Opt 2019 Jun;58(17):4806-4811

A novel, to the best of our knowledge, liquid crystal (LC) biosensor, based on an optical fiber Mach-Zehnder interferometer (MZI), is proposed. The proposed optical fiber MZI consists of two single-mode fibers and a tapered photonic crystal fiber (PCF). The PCF is coated with 4-pentyl-biphenyl-4-carboxylic acid (PBA)-doped 4-cyano-4-pentylbiphenyl (5CB). Being a pH-sensitive material, PBA can manipulate LC molecules to different orientations according to their pH values. When the orientation of LC molecules changes with varying pH, the effective refractive index of the cladding modes also is accordingly affected. Enzymatic reactions of penicillinase can release H, which causes the decrease of the pH. Therefore, the enzymatic reactions of penicillinase can be sensed by monitoring the peak shift in the interference spectrum. The effects of the tapered diameter on the sensitivity of the sensor were experimentally investigated as well.
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http://dx.doi.org/10.1364/AO.58.004806DOI Listing
June 2019

Liquid-crystal based Fabry-Perot interferometer displacement sensor.

Appl Opt 2019 Jan;58(2):410-414

A Fabry-Perot interferometer displacement sensor is proposed and demonstrated. This sensor is prepared by inserting two ceramic ferrules into a polydimethylsiloxane (PDMS) hose to generate a Fabry-Perot cavity. The cavity is filled with nematic liquid crystals (NLCs), which induce a Vernier effect due to the birefringence of NLCs. The flexible PDMS hose makes the cavity length adjustable. A displacement sensor with sensitivity of ∼2.97  nm/μm and a dynamic range of 0.9 mm at the center wavelength of 1550 nm is experimentally demonstrated.
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http://dx.doi.org/10.1364/AO.58.000410DOI Listing
January 2019

Bacterial community assemblages in the rhizosphere soil, root endosphere and cyst of soybean cyst nematode-suppressive soil challenged with nematodes.

FEMS Microbiol Ecol 2018 10;94(10)

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No 3 Park 1, Beichen West Rd., Chaoyang District, Beijing 100101, China.

In disease-suppressive soil, plants rely upon mutualistic associations between roots and specific microbes for nutrient acquisition and disease suppression. Notably, the transmission of suppressiveness by the cysts of sugar beet cyst nematode from suppressive to conducive soils has been previously observed in greenhouse trials. However, our current understanding of the bacterial assemblages in the cyst, root endosphere and rhizosphere soil is still limited. To obtain insights into these bacterial microbiota assemblages, the bacterial communities inhabiting the plant-associated microhabitats and cysts in soybean cyst nematode (SCN)-suppressive soil were characterized by deep sequencing, using soybean grown under growth room conditions with additional SCN challenge. Clustering analysis revealed that the cyst bacterial community was closer to the root endosphere community than to the rhizosphere and bulk soil communities. Interestingly, the cyst bacterial community was initially established by the consecutive selection of bacterial taxa from the soybean root endosphere. We found a set of potential microbial consortia, such as Pasteuria, Pseudomonas, Rhizobium, and other taxa, that were consistently enriched in the rhizocompartments under SCN challenge, and more abundant in the cysts than in the bulk soil. Our results suggest that the soybean root-associated and cyst microbiota may cause the suppressiveness of SCN in suppressive soil.
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http://dx.doi.org/10.1093/femsec/fiy142DOI Listing
October 2018

The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells.

Biochem Pharmacol 2017 12 24;146:87-100. Epub 2017 Oct 24.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Hong Kong Polytechnic University, Hong Kong, China. Electronic address:

Multidrug resistance is the main obstacle in cancer chemotherapy. Emerging evidence demonstrates the important role of autophagy in cancer cell resistance to chemotherapy. Therefore, autophagy inhibition by natural compounds may be a promising strategy for overcoming drug resistance in liver cancer cells. Here, we found that ADCX, a natural cycloartane triterpenoid extracted from the traditional Chinese medicine (TCM) source Cimicifugae rhizoma (Shengma), impaired autophagic degradation by suppressing lysosomal cathepsin B (CTSB) expression in multidrug-resistant liver cancer HepG2/ADM cells, thereby leading to autophagic flux inhibition. Moreover, impairing autophagic flux promoted ADCX-induced apoptotic cell death in HepG2/ADM cells. Interestingly, Akt was overactivated by ADCX treatment, which downregulated CTSB and inhibited autophagic flux. Together, our results provide the first demonstration that an active TCM constituent can overcome multidrug resistance in liver cancer cells via Akt-mediated inhibition of autophagic degradation.
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http://dx.doi.org/10.1016/j.bcp.2017.10.012DOI Listing
December 2017

Pericyte-targeting prodrug overcomes tumor resistance to vascular disrupting agents.

J Clin Invest 2017 Oct 28;127(10):3689-3701. Epub 2017 Aug 28.

College of Pharmacy, and.

Blood vessels in the tumor periphery have high pericyte coverage and are resistant to vascular disrupting agents (VDAs). VDA treatment resistance leads to a viable peripheral tumor rim that contributes to treatment failure and disease recurrence. Here, we provide evidence to support a hypothesis that shifting the target of VDAs from tumor vessel endothelial cells to pericytes disrupts tumor peripheral vessels and the viable rim, circumventing VDA treatment resistance. Through chemical engineering, we developed Z-GP-DAVLBH (from the tubulin-binding VDA desacetylvinblastine monohydrazide [DAVLBH]) as a prodrug that can be selectively activated by fibroblast activation protein α (FAPα) in tumor pericytes. Z-GP-DAVLBH selectively destroys the cytoskeleton of FAPα-expressing tumor pericytes, disrupting blood vessels both within the core and around the periphery of tumors. As a result, Z-GP-DAVLBH treatment eradicated the otherwise VDA-resistant tumor rim and led to complete regression of tumors in multiple lines of xenografts without producing the drug-related toxicity that is associated with similar doses of DAVLBH. This study demonstrates that targeting tumor pericytes with an FAPα-activated VDA prodrug represents a potential vascular disruption strategy in overcoming tumor resistance to VDA treatments.
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http://dx.doi.org/10.1172/JCI94258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617663PMC
October 2017

Arenobufagin inhibits prostate cancer epithelial-mesenchymal transition and metastasis by down-regulating β-catenin.

Pharmacol Res 2017 Sep 14;123:130-142. Epub 2017 Jul 14.

College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drug Research, Jinan University, Guangzhou 510632, PR China. Electronic address:

Epithelial-mesenchymal transition (EMT) plays an important role in prostate cancer (PCa) metastasis; thus, developing EMT inhibitors may be a feasible treatment for metastatic PCa. Here, we discovered that arenobufagin and four other bufadienolides suppressed PC3 cell EMT. These compounds modulated EMT marker expression with elevating E-cadherin and reducing ZEB1, vimentin and slug expression, and attenuated the migration and invasion of PC3 cells. Among these five compounds, arenobufagin exhibited the most potent activity. We found that the mRNA and protein expression of β-catenin and β-catenin/TCF4 target genes, which are related to tumor invasion and metastasis, were down-regulated after arenobufagin treatment. Overexpression of β-catenin in PC3 cells antagonized the EMT inhibition effect of arenobufagin, while silencing β-catenin with siRNA enhanced the inhibitory effect of arenobufagin on EMT. In addition, arenobufagin restrained xenograft tumor EMT, as demonstrated by decreased mesenchymal marker expression and increased epithelial marker expression, and reduced the tumor metastatic foci in lung. This study demonstrates a novel anticancer activity of arenobufagin, which inhibits PC3 cell EMT by down-regulating β-catenin, thereby reducing PCa metastasis. In addition, it also provides new evidence for the development of arenobufagin as a treatment for metastatic prostate cancer.
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http://dx.doi.org/10.1016/j.phrs.2017.07.009DOI Listing
September 2017

In vitro and in vivo antiangiogenic activity of desacetylvinblastine monohydrazide through inhibition of VEGFR2 and Axl pathways.

Am J Cancer Res 2016 15;6(4):843-58. Epub 2016 Mar 15.

College of Pharmacy, Jinan University Guangzhou 510632, China.

Tumor angiogenic process is regulated by multiple proangiogenic pathways, such as vascular endothelial growth factor receptor 2 (VEGFR2) and Axl receptor tyrosine kinase (Axl). Axl is one of many important factors involved in anti-VEGF resistance. Inhibition of VEGF/VEGFR2 signaling pathway alone fails to block tumor neovascularization. Therefore, discovery of novel agents targeting multiple angiogenesis pathways is in demand. Desacetylvinblastine monohydrazide (DAVLBH), a derivative of vinblastine (VLB), has been reported exhibit an anticancer activity via its cytotoxic effect. However, little attention has been paid to the antiangiogenic properties of DAVLBH. Here, we firstly reported that DAVLBH exerted a more potent antiangiogenic effect than VLB in vitro and in vivo, which was associated with inactivation of VEGF/VEGFR2 and Gas6/Axl signaling pathways. We found that DAVLBH inhibited VEGF- and Gas6-induced HUVECs proliferation, migration, tube formation and vessel sprouts formation in vitro and ex vivo. It significantly inhibited in vivo tumor angiogenesis and tumor growth in HeLa xenografts. It also inhibited Gas6-induced pericytes recruitment to endothelial tubes accompanied with a decrease in expression and activation of Axl. Besides, it could block the compensatory up-regulating expression and activation of Axl in response to bevacizumab treatment in HUVECs. Taken together, our results suggest that DAVLBH potently inhibits angiogenesis-mediated tumor growth through blockage of the activation of VEGF/VEGFR2 and Gas6/Axl pathways and it might serve as a promising antiangiogenic agent for the cancer therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859888PMC
May 2016

Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo.

Sci Rep 2015 Nov 3;5:16185. Epub 2015 Nov 3.

Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.

While searching for natural anti-hepatocellular carcinoma (HCC) components in Ailanthus altissima, we discovered that ailanthone had potent antineoplastic activity against HCC. However, the molecular mechanisms underlying the antitumor effect of ailanthone on HCC have not been examined. In this study, the antitumor activity and the underlying mechanisms of ailanthone were evaluated in vitro and in vivo. Mechanistic studies showed that ailanthone induced G0/G1-phase cell cycle arrest, as indicated by decreased expression of cyclins and CDKs and increased expression of p21 and p27. Our results demonstrated that ailanthone triggered DNA damage characterized by activation of the ATM/ATR pathway. Moreover, ailanthone-induced cell death was associated with apoptosis, as evidenced by an increased ratio of cells in the subG1 phase and by PARP cleavage and caspase activation. Ailanthone-induced apoptosis was mitochondrion-mediated and involved the PI3K/AKT signaling pathway in Huh7 cells. In vivo studies demonstrated that ailanthone inhibited the growth and angiogenesis of tumor xenografts without significant secondary adverse effects, indicating its safety for treating HCC. In conclusion, our study is the first to report the efficacy of ailanthone against Huh7 cells and to elucidate its underlying molecular mechanisms. These findings suggest that ailanthone is a potential agent for the treatment of liver cancer.
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http://dx.doi.org/10.1038/srep16185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630794PMC
November 2015

Optimal dose of zinc supplementation for preventing aluminum-induced neurotoxicity in rats.

Neural Regen Res 2013 Oct;8(29):2754-62

Department of Nutrition, Institute of Health & Environmental Medicine, Academy of Military Medical Sciences, Tianjin 300050, China.

Zinc supplementation can help maintain learning and memory function in rodents. In this study, we hypothesized that zinc supplementation could antagonize the neurotoxicity induced by aluminum in rats. Animals were fed a diet containing different doses of zinc (50, 100, 200 mg/kg) for 9 weeks, and orally administered aluminum chloride (300 mg/kg daily) from the third week for 7 consecutive weeks. Open-field behavioral test results showed that the number of rearings in the group given the 100 mg/kg zinc supplement was significantly increased compared with the group given the 50 mg/kg zinc supplement. Malondialdehyde content in the cerebrum was significantly decreased, while dopamine and 5-hydroxytryptamine levels were increased in the groups given the diet supplemented with 100 and 200 mg/kg zinc, compared with the group given the diet supplemented with 50 mg/kg zinc. The acetylcholinesterase activity in the cerebrum was significantly decreased in the group given the 100 mg/kg zinc supplement. Hematoxylin-eosin staining revealed evident pathological damage in the hippocampus of rats in the group given the diet supplemented with 50 mg/kg zinc, but the damage was attenuated in the groups given the diet supplemented with 100 and 200 mg/kg zinc. Our findings suggest that zinc is a potential neuroprotective agent against aluminum-induced neurotoxicity in rats, and the optimal dosages are 100 and 200 mg/kg.
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http://dx.doi.org/10.3969/j.issn.1673-5374.2013.29.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145991PMC
October 2013

Effects of environmental conditions on the release of phosphorus from biochar.

Chemosphere 2013 Nov 16;93(9):2069-75. Epub 2013 Aug 16.

Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.

Biochar, the byproduct from fast pyrolysis of waste biomass, is widely used as a soil conditioner. The phosphorus in biochar is not only a P source for plant growth, but also an important factor caused the eutrophication of water. Here, the effects of environmental conditions on the release of different P species from biochar in a biochar-water system were investigated. About 2.2 mg g(-1) P in the form of inorganic orthophosphate and pyrophosphate was released from a raw biochar (contained 4.7 mg P g(-1)) at initial pH of 9.0 in the initial 8h. The release of orthophosphate was significantly enhanced from 0.64 to 1.35 mg g(-1) by the coexisting anions of Cl(-), NO3(-) or SO4(2-) due to the effect of ion exchange competition, while the release of pyrophosphate (P2O7(4-)) was not influenced by the introduction of anions which might be attributed to the formation of stable complexes. The introduction of Hoagland nutrient solution led to the decrease in release of P due to the formation of precipitates between dissolved P and excessive Ca(2+) and Mg(2+).
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http://dx.doi.org/10.1016/j.chemosphere.2013.07.041DOI Listing
November 2013

UV nonlinear optical crystal Ba2[B6O9(OH)4] featuring unique chiral layers with a new B18O42 circle based on BO3 and BO4 units.

Inorg Chem 2012 Feb 19;51(3):1852-8. Epub 2012 Jan 19.

Xinjiang Key Laboratory of Electronic Information Materials and Devices, Xinjiang Technical Institute of Physics & Chemistry, Chinese Academy of Sciences, 40-1 South Beijing Road, Urumqi 830011, China.

A new noncentrosymmetric polyborate, Ba(2)[B(6)O(9)(OH)(4)], has been synthesized under a hydrothermal condition. The polyborate contains chiral layers constructed by two kinds of helical chains and also form new B(18)O(42) circles based on B(3)O(8) units [(3: Δ+2T)]. One kind of Ba atom locates in the cavity surrounded by the B(11)O(11) ring within the anion layer, and the other kind of Ba atom inserts between two adjacent layers. UV-vis diffuse reflectance spectroscopy demonstrates that the compound has a cutoff edge below 190 nm and has a large second-harmonic generation (SHG) effect, which is approximately 3 times that of KH(2)PO(4) (KDP) and is type-I phase matchable.
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http://dx.doi.org/10.1021/ic2021337DOI Listing
February 2012

Long-term ex vivo monitoring of in vivo microRNA activity in liver using a secreted luciferase sensor.

Sci China Life Sci 2011 May 15;54(5):418-25. Epub 2011 May 15.

State Key Laboratory of Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 100052, China.

Technology for monitoring in vivo microRNA (miRNA) activity is extremely important for elucidating miRNA biology. However, in vivo studies of miRNA have been hampered by the lack of a convenient approach to reliably reflect real-time functional changes in miRNAs. Sensors for miRNA were developed by adding miRNA target sequences to the 3'-untranslated region of Gaussia princeps luciferase (Gluc) mRNA. These sensors were then evaluated in vitro and in vivo by measuring Gluc activity in cell supernatants and in peripheral blood. Sensors driven by the CMV promoter were effective for monitoring miR-122 in living cells, but not for the long-term monitoring of miR-122 or miR-142 in mouse liver because of CMV-promoter silencing. Replacing the CMV promoter with a CAG promoter rendered these sensors effective for the long-term monitoring of relevant liver miRNA activities. We subsequently used the CAG-promoter-based sensor for the long-term monitoring of endogenous liver miR-122, miR142 and miR-34a activities, as well as for exogenous miR-34a activity. Our study demonstrates that real-time in vivo activities of miRNAs can be continuously and conveniently detected in mouse liver using the sensors that we have developed.
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http://dx.doi.org/10.1007/s11427-011-4171-0DOI Listing
May 2011