Evidence map›Paper›PMID 26582795›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

MicroRNA-3151 inactivates TP53 in BRAF-mutated human malignancies.

Malori A Lankenau, Ravi Patel, Sandya Liyanarachchi, Sophia E Maharry, Kevin W Hoag, Megan Duggan, Christopher J Walker, Joseph Markowitz, William E Carson, Ann-Kathrin Eisfeld and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. UnravelingCancer drug resistance (Alhambra, Calif.) · 2025
    Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. MicroRNA-Directed Cancer Therapies: Implications in Melanoma Intervention.The Journal of pharmacology and experimental therapeutics · 2018
    Review
  10. Article
  11. MicroRNAs in the thyroid.Best practice & research. Clinical endocrinology & metabolism · 2016
    Review
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

11 authors at 1 institution in 1 country.

Malori A LankenauThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
Ravi PatelThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
Sandya LiyanarachchiThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
Sophia E MaharryThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
Kevin W HoagThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
Megan DugganThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
Christopher J WalkerThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
Joseph MarkowitzThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
William E CarsonThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
Ann-Kathrin EisfeldThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210 albert.delachapelle@osumc.edu ann-kathrin.eisfeld@osumc.edu.
Albert de la ChapelleThe Ohio State University Comprehensive Cancer Center, Columbus, OH 43210 albert.delachapelle@osumc.edu ann-kathrin.eisfeld@osumc.edu.
The Ohio State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
Selective Modulation of Thyroidal RadioiodineP01CA124570 · NCI · OHIO STATE UNIVERSITY · PI RINGEL, MATTHEW D · 2008 to 2017
$23.4M
Integrative Training in Biomedical SystemsT32GM068412 · NIGMS · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2005 to 2020
$2.4M
NCI NIH HHS P01 CA124570NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA16058NIGMS NIH HHS T32 GM068412
6 · The paper itself

Abstract

The B-Raf proto-oncogene serine/threonine kinase (BRAF) gene is the most frequently mutated gene in malignant melanoma (MM) and papillary thyroid cancer (PTC) and is causally involved in malignant cell transformation. Mutated BRAF is associated with an aggressive disease phenotype, thus making it a top candidate for targeted treatment strategies in MM and PTC. We show that BRAF mutations in both MM and PTC drive increased expression of oncomiR-3151, which is coactivated by the SP1/NF-κB complex. Knockdown of microRNA-3151 (miR-3151) with short hairpin RNAs reduces cell proliferation and increases apoptosis of MM and PTC cells. Using a targeted RNA sequencing approach, we mechanistically determined that miR-3151 directly targets TP53 and other members of the TP53 pathway. Reducing miR-3151's abundance increases TP53's mRNA and protein expression and favors its nuclear localization. Consequently, knockdown of miR-3151 also leads to caspase-3-dependent apoptosis. Simultaneous inhibition of aberrantly activated BRAF and knockdown of miR-3151 potentiates the effects of sole BRAF inhibition with the BRAF inhibitor vemurafenib and may provide a novel targeted therapeutic approach in BRAF-mutated MM and PTC patients. In conclusion, we identify miR-3151 as a previously unidentified player in MM and PTC pathogenesis, which is driven by BRAF-dependent and BRAF-independent mechanisms. Characterization of TP53 as a downstream effector of miR-3151 provides evidence for a causal link between BRAF mutations and TP53 inactivation.

Indexed as

MutationActive Transport, Cell NucleusCarcinomaCarcinoma, PapillaryHumansIndolesMelanomaMicroRNAsNF-kappa BProto-Oncogene MasProto-Oncogene Proteins B-rafSulfonamidesThyroid Cancer, PapillaryThyroid NeoplasmsTumor Suppressor Protein p53VemurafenibBRAF protein, humanIndolesMAS1 protein, humanMicroRNAsMIRN3151 microRNA, humanNF-kappa BProto-Oncogene MasProto-Oncogene Proteins B-rafSulfonamidesTP53 protein, humanTumor Suppressor Protein p53VemurafenibBRAFmelanomamicroRNAPTCTP53

Identifiers

PMID26582795
PMCPMC4679059
OpenAlexW2285192267

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.