ArticleThe Journal of pharmacology and experimental therapeutics2015
Bioengineering Novel Chimeric microRNA-34a for Prodrug Cancer Therapy: High-Yield Expression and Purification, and Structural and Functional Characterization.
Open access · bronzeAbstract read
In one paragraph
Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Design, expression, purification, and application of novel recombinant miR-491 molecules to define the biogenesis and function of miR-491-3p versus -5p in posttranscriptional regulation of UDP-glucuronosyltransferase 1A1.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Efficiency and safety of five different agents forFrontiers in molecular biosciences · 2026Article
- A reference-guided iterative approach to polish the nanopore sequencing basecalling for therapeutic RNA quality control.Communications biology · 2025Article
- Bioengineered miR-7-5p modulates non-small cell lung cancer cell metabolism to improve therapy.Molecular pharmacology · 2025Article
- The Precise Basecalling of Short-Read Nanopore Sequencing.bioRxiv : the preprint server for biology · 2024Article
- Molecular Engineering of Functional SiRNA Agents.ACS synthetic biology · 2024Article
- Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy.Nature communications · 2024Article
- Efflux ABC transporters in drug disposition and their posttranscriptional gene regulation by microRNAs.Frontiers in pharmacology · 2024Review
- Use of recombinant microRNAs as antimetabolites to inhibit human non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2023Article
- RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.The Journal of pharmacology and experimental therapeutics · 2023Review
- Recent Advances in Novel Recombinant RNAs for Studying Post-transcriptional Gene Regulation in Drug Metabolism and Disposition.Current drug metabolism · 2023Review
- Gut Microbiota-MicroRNA Interactions in Intestinal Homeostasis and Cancer Development.Microorganisms · 2022Review
- Bioengineered BERA-Wnt5a siRNA Targeting Wnt5a/FZD2 Signaling Suppresses Advanced Prostate Cancer Tumor Growth and Enhances Enzalutamide Treatment.Molecular cancer therapeutics · 2022Article
- Mir-34a: a regulatory hub with versatile functions that controls osteosarcoma networks.Cell cycle (Georgetown, Tex.) · 2022Review
- Bioengineered miR-34a modulates mitochondrial inner membrane protein 17 like 2 (MPV17L2) expression toward the control of cancer cell mitochondrial functions.Bioengineered · 2022Article
- A CGA/EGFR/GATA2 positive feedback circuit confers chemoresistance in gastric cancer.The Journal of clinical investigation · 2022Article
- Deliver the promise: RNAs as a new class of molecular entities for therapy and vaccination.Pharmacology & therapeutics · 2022Review
- Bioengineered RNA Therapy in Patient-Derived Organoids and Xenograft Mouse Models.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Global trends in research on miRNA-microbiome interaction from 2011 to 2021: A bibliometric analysis.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Wei-Peng WangDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Pui Yan HoDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Qiu-Xia ChenDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Balasubrahmanyam AddepalliDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Patrick A LimbachDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Mei-Mei LiDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Wen-Juan WuDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Joseph L JilekDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Jing-Xin QiuDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Hong-Jian ZhangDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Tianhong LiDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Theodore WunDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Ralph DeVere WhiteDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Kit S LamDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.).
Ai-Ming YuDepartment of Biochemistry and Molecular Medicine (W.-P.W., P.Y.H., Q.-X.C., M.-M.L., W.-J.W., J.L.J., K.S.L., A.-M.Y.), Division of Hematology Oncology (T.L., T.W., K.S.L.) and Department of Urology (R.D.W.), School of Medicine, University of California-Davis, Sacramento, California; Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio (B.A., P.A.L.); Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York (J.-X.Q.); and Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China (W.-P.W., H.-J.Z.) aimyu@ucdavis.edu.
University of California, Davis · USUniversity of Cincinnati · USRoswell Park Comprehensive Cancer Center · USSoochow University · CN
Funding
LCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., KISSELA, BRETT M · 2015 to 2024
$37.5MPredoctoral Training in Pharmacological SciencesT32GM099608 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HELL, JOHANNES W · 2012 to 2021
$2.2MMicroRNA-1291 in Regulation of Xenobiotic Disposition and Cell DifferentiationU01CA175315 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI YU, AIMING · 2014 to 2018
$1.6MNCATS NIH HHS UL1 TR001425NCI NIH HHS 1U01-CA175315NCI NIH HHS U01 CA175315NIGMS NIH HHS T32 GM099608
Abstract
Development of anticancer treatments based on microRNA (miRNA/miR) such as miR-34a replacement therapy is limited to the use of synthetic RNAs with artificial modifications. Herein, we present a new approach to a high-yield and large-scale biosynthesis, in Escherichia coli using transfer RNA (tRNA) scaffold, of chimeric miR-34a agent, which may act as a prodrug for anticancer therapy. The recombinant tRNA fusion pre-miR-34a (tRNA/mir-34a) was quickly purified to a high degree of homogeneity (>98%) using anion-exchange fast protein liquid chromatography, whose primary sequence and post-transcriptional modifications were directly characterized by mass spectrometric analyses. Chimeric tRNA/mir-34a showed a favorable cellular stability while it was degradable by several ribonucleases. Deep sequencing and quantitative real-time polymerase chain reaction studies revealed that tRNA-carried pre-miR-34a was precisely processed to mature miR-34a within human carcinoma cells, and the same tRNA fragments were produced from tRNA/mir-34a and the control tRNA scaffold (tRNA/MSA). Consequently, tRNA/mir-34a inhibited the proliferation of various types of human carcinoma cells in a dose-dependent manner and to a much greater degree than the control tRNA/MSA, which was mechanistically attributable to the reduction of miR-34a target genes. Furthermore, tRNA/mir-34a significantly suppressed the growth of human non-small-cell lung cancer A549 and hepatocarcinoma HepG2 xenograft tumors in mice, compared with the same dose of tRNA/MSA. In addition, recombinant tRNA/mir-34a had no or minimal effect on blood chemistry and interleukin-6 level in mouse models, suggesting that recombinant RNAs were well tolerated. These findings provoke a conversation on producing biologic miRNAs to perform miRNA actions, and point toward a new direction in developing miRNA-based therapies.
Indexed as
AnimalsAntineoplastic AgentsBioengineeringCell Line, TumorCell SurvivalDose-Response Relationship, DrugHep G2 CellsHumansMiceMice, Inbred BALB CMice, NudeMicroRNAsProdrugsStructure-Activity RelationshipXenograft Model Antitumor AssaysAntineoplastic AgentsMicroRNAsMIRN34 microRNA, humanProdrugs
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.