Evidence mapPaperPMID 39769278Full record

ArticleInternational journal of molecular sciences2024

Oncogenic Functions of Alternatively Spliced

Fernanda Costas C de Faria, Safiya Khurshid, Patricia Sarchet, Sayumi Tahara, Lucia Casadei, Valerie Grignol, Roma Karna, Sydney Rentsch, Nipin Sp, Joal D Beane and 8 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

18 authors.

Fernanda Costas C de FariaThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Safiya KhurshidCenter for Childhood Cancer Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205, USA.
Patricia SarchetThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Sayumi TaharaThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Lucia CasadeiThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Valerie GrignolThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0002-8574-0715
Roma KarnaThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Sydney RentschThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Nipin SpThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Joal D BeaneThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Luciano MazzoccoliDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Research, Columbus, OH 43210, USA.
Matias MontesCenter for Childhood Cancer Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205, USA.ORCID 0000-0003-3637-6379
Giovanni NigitaDepartment of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.ORCID 0000-0001-8880-4334
Joe T SharickDepartment of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA.
Jennifer L LeightDepartment of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA.ORCID 0000-0003-4510-1086
Federica CaloreThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Dawn S ChandlerCenter for Childhood Cancer Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205, USA.ORCID 0000-0003-0670-9806
Raphael E PollockThe James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0002-0443-1583

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Amanda Ewart Toland · 1985 to 2026
$132.3M
Mdm2 Alternative Splicing in DNA Damage and CancerR01CA262873 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI CHANDLER, DAWN S · 2021 to 2025
$2.4M
NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA262873NIH Cancer Center Support P30CA016058NIH HHS 1R01CA262873United States Department of Defense W81XWH-22-1-0530
6 · The paper itself

Abstract

Retroperitoneal liposarcoma (RPLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS). Complete surgical resection remains the mainstay treatment, while the high rate of locoregional recurrence constitutes the predominant cause of mortality. Well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are the most frequent subtypes of RPLPS and present amplified MDM2 gene as a hallmark. However, there are few reports evaluating the role of alternatively spliced MDM2 transcripts in RPLPS. In this study, we assessed MDM2-ALT2 expression levels in a cohort of RPLPS patients and evaluated the biological functions of the MDM2-ALT2 isoform in vitro in DDLPS cell lines. Using BaseScope™ and qPCR, we demonstrated that MDM2-Full Length (MDM2-FL) and MDM2-ALT2 expression levels were upregulated in RPLPS patient-derived tissue samples compared to normal adjacent to tumor tissue (NAT). DDLPS cells overexpressing MDM2-FL or MDM2-ALT2 had higher proliferation rates and increased migration and invasion capacities, as well as increased protein levels of p-AKT, mTOR, p70S6K, MMP2, and cJun. Simultaneous overexpression of MDM2-ALT2 and AKT silencing showed that AKT inhibition impaired p-p70S6K and MMP2 protein increased levels and led to significantly decreased proliferation and migration rates compared to cells overexpressing MDM2-ALT2 only. Taken together, our data suggest that MDM2-ALT2 may promote RPLPS progression.

Indexed as

Alternative SplicingCell ProliferationLiposarcomaProtein IsoformsProto-Oncogene Proteins c-mdm2Retroperitoneal NeoplasmsAgedCell Line, TumorCell MovementFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedMDM2 protein, humanProtein IsoformsProto-Oncogene Proteins c-mdm2AKTDDLPSMDM2-ALT2MDM2-Full lengthMDM2 variantssoft tissue sarcomaWDLPS

Identifiers

PMID39769278
PMCPMC11676768

What Socratic 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 Socratic graph.