Evidence map›Paper›PMID 31879968›Full record

ArticleHepatology (Baltimore, Md.)2020

Modulation of Biliary Cancer Chemo-Resistance Through MicroRNA-Mediated Rewiring of the Expansion of CD133+ Cells.

Pietro Carotenuto, Somaieh Hedayat, Matteo Fassan, Vincenzo Cardinale, Andrea Lampis, Vincenza Guzzardo, Caterina Vicentini, Aldo Scarpa, Luciano Cascione, Daniele Costantini and 26 more

Open access · hybridAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 4% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
  2. Lipopolysaccharide promotes rheumatoid arthritis by enhancing Wnt7b mediated macrophage-FLS communication.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 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

36 authors at 10 institutions in 3 countries.

Pietro CarotenutoDivision of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.
Somaieh HedayatDivision of Molecular Pathology, Institute of Cancer Research, London, United Kingdom.
Matteo FassanDepartment of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy.
Vincenzo CardinaleDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
Andrea LampisDivision of Molecular Pathology, Institute of Cancer Research, London, United Kingdom.
Vincenza GuzzardoDepartment of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy.
Caterina VicentiniDepartment of Pathology, University of Verona, Verona, Italy.
Aldo ScarpaDepartment of Pathology, University of Verona, Verona, Italy.
Luciano CascioneBioinformatics Core Unit, Institute of Oncology Research, Bellinzona, Switzerland.
Daniele CostantiniDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.ORCID 0000-0001-7438-4578
Guido CarpinoDepartment of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy.
Domenico AlvaroDepartment of Translational and Precision Medicine, Sapienza University, Rome, Italy.
Michele GhidiniDivision of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.
Francesco TrevisaniDivision of Molecular Pathology, Institute of Cancer Research, London, United Kingdom.
Robert Te PoeleDivision of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.
Massimiliano SalatiDivision of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.
Sofia VenturaDivision of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.
Georgios VlachogiannisDivision of Molecular Pathology, Institute of Cancer Research, London, United Kingdom.
Jens C HahneDivision of Molecular Pathology, Institute of Cancer Research, London, United Kingdom.
Luke BoulterMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom.
Stuart J ForbesCenter for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Rachel V GuestCenter for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Umberto CilloDepartment of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy.
Ian Said-HuntingfordDivision of Molecular Pathology, Institute of Cancer Research, London, United Kingdom.
Ruwaida BegumThe Royal Marsden NHS Trust Surrey and London, Sutton, United Kingdom.
Elizabeth SmythThe Royal Marsden NHS Trust Surrey and London, Sutton, United Kingdom.
Vasiliki MichalareaThe Royal Marsden NHS Trust Surrey and London, Sutton, United Kingdom.
David CunninghamThe Royal Marsden NHS Trust Surrey and London, Sutton, United Kingdom.
Lorenza RimassaMedical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy.
Armando SantoroMedical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy.
Massimo RoncalliDepartment of Pathology, Humanitas Research Hospital & Hunimed University, Rozzano, Italy.
Vladimir KirkinDivision of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.
Paul ClarkeDivision of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.
Paul WorkmanDivision of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.
Nicola ValeriDivision of Molecular Pathology, Institute of Cancer Research, London, United Kingdom.
Chiara BraconiDivision of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.
Institute of Cancer Research · GBRoyal Marsden NHS Foundation Trust · GBSapienza University of Rome · ITUniversity of Padua · ITUniversity of Verona · ITMRC Centre for Regenerative Medicine · GBForo Italico University of Rome · ITHumanitas University · ITInstitute of Genetics and Cancer · GBInstitute of Oncology Research · CH

Funding

Cancer Research UK 18052Cancer Research UK 22897Cancer Research UK CDF TO NVCancer Research UK CRUK FUNDED CANCER THERAPEUTICS UNIT AT ICRCancer Research UK PW is a CRUK Life FellowDepartment of Health BRC to ICR/Marsden
6 · The paper itself

Abstract

BACKGROUND AND

aimsChanges in single microRNA (miRNA) expression have been associated with chemo-resistance in biliary tract cancers (BTCs). However, a global assessment of the dynamic role of the microRNome has never been performed to identify potential therapeutic targets that are functionally relevant in the BTC cell response to chemotherapy. APPROACH AND

resultsHigh-throughput screening (HTS) of 997 locked nucleic acid miRNA inhibitors was performed in six cholangiocarcinoma cell lines treated with cisplatin and gemcitabine (CG) seeking changes in cell viability. Validation experiments were performed with mirVana probes. MicroRNA and gene expression was assessed by TaqMan assay, RNA-sequencing, and in situ hybridization in four independent cohorts of human BTCs. Knockout of microRNA was achieved by CRISPR-CAS9 in CCLP cells (MIR1249KO) and tested for effects on chemotherapy sensitivity in vitro and in vivo. HTS revealed that MIR1249 inhibition enhanced chemotherapy sensitivity across all cell lines. MIR1249 expression was increased in 41% of cases in human BTCs. In validation experiments, MIR1249 inhibition did not alter cell viability in untreated or dimethyl sulfoxide-treated cells; however, it did increase the CG effect. MIR1249 expression was increased in CD133+ biliary cancer cells freshly isolated from the stem cell niche of human BTCs as well as in CD133+ chemo-resistant CCLP cells. MIR1249 modulated the chemotherapy-induced enrichment of CD133+ cells by controlling their clonal expansion through the Wnt-regulator FZD8. MIR1249KO cells had impaired expansion of the CD133+ subclone and its enrichment after chemotherapy, reduced expression of cancer stem cell markers, and increased chemosensitivity. MIR1249KO xenograft BTC models showed tumor shrinkage after exposure to weekly CG, whereas wild-type models showed only stable disease over treatment.

conclusionsMIR1249 mediates resistance to CG in BTCs and may be tested as a target for therapeutics.

Indexed as

Biliary Tract NeoplasmsCholangiocarcinomaMicroRNAsAntineoplastic AgentsCell Line, TumorCell ProliferationCell SurvivalCisplatinCRISPR-Cas SystemsDeoxycytidineDrug DiscoveryDrug Resistance, NeoplasmGemcitabineGene Expression Regulation, NeoplasticHigh-Throughput Screening AssaysHumansAntineoplastic AgentsCisplatinDeoxycytidineGemcitabineMicroRNAsMIRN1249 microRNA, human

Identifiers

PMID31879968
PMCPMC7590111
OpenAlexW2997759305

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.