Evidence map›Paper›PMID 36597126›Full record

ArticleMolecular cancer2023

MicroRNA-1 attenuates the growth and metastasis of small cell lung cancer through CXCR4/FOXM1/RRM2 axis.

Parvez Khan, Jawed Akhtar Siddiqui, Prakash G Kshirsagar, Ramakanth Chirravuri Venkata, Shailendra Kumar Maurya, Tamara Mirzapoiazova, Naveenkumar Perumal, Sanjib Chaudhary, Ranjana Kumari Kanchan, Mahek Fatima and 11 more

Open access · goldAbstract read
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In one paragraph

Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 2 pooled it
19.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.

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  16. FOXO3 upregulates and activates GSDME to trigger myeloma cell pyroptosis.International journal of biological sciences · 2026
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  17. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 3 institutions in 1 country.

Parvez KhanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Jawed Akhtar SiddiquiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Prakash G KshirsagarDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Ramakanth Chirravuri VenkataDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Shailendra Kumar MauryaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Tamara MirzapoiazovaDepartment of Medical Oncology and Therapeutics Research, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, 91010, USA.
Naveenkumar PerumalDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Sanjib ChaudharyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Ranjana Kumari KanchanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Mahek FatimaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Md Arafat KhanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Asad Ur RehmanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Imayavaramban LakshmananDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Sidharth MahapatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Geoffrey A TalmonDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Prakash KulkarniDepartment of Medical Oncology and Therapeutics Research, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, 91010, USA.
Apar K GantiDivision of Oncology-Hematology, Department of Internal Medicine, VA-Nebraska Western Iowa Health Care System, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Maneesh JainDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Ravi SalgiaDepartment of Medical Oncology and Therapeutics Research, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, 91010, USA.
Surinder Kumar BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Mohd Wasim NasserDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA. wasim.nasser@unmc.edu.
University of Nebraska Medical Center · USCity Of Hope National Medical Center · USVA Nebraska Western Iowa Health Care System · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI John Charles Williams · 1985 to 2026
$86.3M
Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI THAYER, SARAH P · 2018 to 2022
$8.1M
Modulation of Tumor Microenvironment for Improved Therapy of Pancreatic CancerR01CA247471 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., JAIN, MANEESH · 2020 to 2024
$2.8M
Novel approach to attenuate small cell lung cancer growth and metastasisR01CA218545 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI NASSER, MOHD WASIM · 2018 to 2022
$2.6M
Targeting MUC5AC mucin in breast cancer brain metastasisR01CA241752 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI NASSER, MOHD WASIM · 2021 to 2025
$2.3M
Targeted Radiation Therapy for Pancreatic CancerR01CA195586 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., JAIN, MANEESH · 2015 to 2019
$2.2M
NCI NIH HHS P01 CA217798NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA195586NCI NIH HHS R01 CA218545NCI NIH HHS R01 CA241752NCI NIH HHS R01 CA247471NIH HHS R01CA218545NIH HHS R01CA247471
6 · The paper itself

Abstract

backgroundSmall cell lung cancer (SCLC) is an aggressive lung cancer subtype that is associated with high recurrence and poor prognosis. Due to lack of potential drug targets, SCLC patients have few therapeutic options. MicroRNAs (miRNAs) provide an interesting repertoire of therapeutic molecules; however, the identification of miRNAs regulating SCLC growth and metastasis and their precise regulatory mechanisms are not well understood.

methodsTo identify novel miRNAs regulating SCLC, we performed miRNA-sequencing from donor/patient serum samples and analyzed the bulk RNA-sequencing data from the tumors of SCLC patients. Further, we developed a nanotechnology-based, highly sensitive method to detect microRNA-1 (miR-1, identified miRNA) in patient serum samples and SCLC cell lines. To assess the therapeutic potential of miR-1, we developed various in vitro models, including miR-1 sponge (miR-1Zip) and DOX-On-miR-1 (Tet-ON) inducible stable overexpression systems. Mouse models derived from intracardiac injection of SCLC cells (miR-1Zip and DOX-On-miR-1) were established to delineate the role of miR-1 in SCLC metastasis. In situ hybridization and immunohistochemistry were used to analyze the expression of miR-1 and target proteins (mouse and human tumor specimens), respectively. Dual-luciferase assay was used to validate the target of miR-1, and chromatin immunoprecipitation assay was used to investigate the protein-gene interactions.

resultsA consistent downregulation of miR-1 was observed in tumor tissues and serum samples of SCLC patients compared to their matched normal controls, and these results were recapitulated in SCLC cell lines. Gain of function studies of miR-1 in SCLC cell lines showed decreased cell growth and oncogenic signaling, whereas loss of function studies of miR-1 rescued this effect. Intracardiac injection of gain of function of miR-1 SCLC cell lines in the mouse models showed a decrease in distant organ metastasis, whereas loss of function of miR-1 potentiated growth and metastasis. Mechanistic studies revealed that CXCR4 is a direct target of miR-1 in SCLC. Using unbiased transcriptomic analysis, we identified CXCR4/FOXM1/RRM2 as a unique axis that regulates SCLC growth and metastasis. Our results further showed that FOXM1 directly binds to the RRM2 promoter and regulates its activity in SCLC.

conclusionsOur findings revealed that miR-1 is a critical regulator for decreasing SCLC growth and metastasis. It targets the CXCR4/FOXM1/RRM2 axis and has a high potential for the development of novel SCLC therapies. MicroRNA-1 (miR-1) downregulation in the tumor tissues and serum samples of SCLC patients is an important hallmark of tumor growth and metastasis. The introduction of miR-1 in SCLC cell lines decreases cell growth and metastasis. Mechanistically, miR-1 directly targets CXCR4, which further prevents FOXM1 binding to the RRM2 promoter and decreases SCLC growth and metastasis.

Indexed as

Lung NeoplasmsMicroRNAsSmall Cell Lung CarcinomaAnimalsCell Line, TumorCell ProliferationForkhead Box Protein M1Gene Expression Regulation, NeoplasticHumansMiceReceptors, CXCR4CXCR4 protein, humanForkhead Box Protein M1FOXM1 protein, humanMicroRNAsMIRN1 microRNA, humanMirn1 microRNA, mouseReceptors, CXCR4CXCR4FOXM1microRNAsNeuroendocrine carcinomaRRM2Small cell lung cancer

Identifiers

PMID36597126
PMCPMC9811802
OpenAlexW4313544993

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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.