Evidence map›Paper›PMID 27708228›Full record

ArticleOncotarget2016

SIRT1-mediated downregulation of p27Kip1 is essential for overcoming contact inhibition of Kaposi's sarcoma-associated herpesvirus transformed cells.

Meilan He, Hongfeng Yuan, Brandon Tan, Rosemary Bai, Heon Seok Kim, Sangsu Bae, Lu Che, Jin-Soo Kim, Shou-Jiang Gao

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
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  8. CRISPR/Cas9-Mediated Knockout andJournal of virology · 2019
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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

9 authors at 4 institutions in 2 countries.

Meilan HeDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California Los Angeles, Los Angeles, CA, USA.
Hongfeng YuanDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California Los Angeles, Los Angeles, CA, USA.
Brandon TanDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California Los Angeles, Los Angeles, CA, USA.
Rosemary BaiDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California Los Angeles, Los Angeles, CA, USA.
Heon Seok KimCenter for Genome Engineering, Institute for Basic Science, Seoul, South Korea.
Sangsu BaeCenter for Genome Engineering, Institute for Basic Science, Seoul, South Korea.
Lu CheDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California Los Angeles, Los Angeles, CA, USA.
Jin-Soo KimCenter for Genome Engineering, Institute for Basic Science, Seoul, South Korea.
Shou-Jiang GaoDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California Los Angeles, Los Angeles, CA, USA.
University of Southern California · USHanyang University · KRInstitute for Basic Science · KRSeoul National University · KR

Funding

Cell Model for KSHV Infection and Genetic ManipulationR01CA096512 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Shou-Jiang Gao · 2003 to 2026
$7.4M
Roles of the K3 and K5 in KSHV Persistence and PathogenesisP01CA180779 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2013 to 2017
$7.3M
Regulation of KSHV replication by N6-methyladenosine (m6A) - Diversity SupplementR01CA124332 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI GAO, SHOU-JIANG · 2007 to 2025
$5.0M
Mechanism of KSHV-induced angiogenesisR01CA132637 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI GAO, SHOU-JIANG · 2008 to 2020
$3.6M
HISTONE MODIFIERS IN ORAL KSHV INFECTION AND MALIGNANCIESR01DE025465 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAO, SHOU-JIANG · 2015 to 2019
$2.0M
Targeting KSHV malignancies and persistent infectionR01CA197153 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAO, SHOU-JIANG · 2015 to 2019
$1.9M
Oral KSHV Complications in HIV InfectionR01DE017333 · NIDCR · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI GAO, SHOU-JIANG · 2005 to 2007
$961k
KSHV microRNAs in cellular transformation and tumorigenesisR01CA177377 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAO, SHOU-JIANG · 2013 to 2015
$596k
NCI NIH HHS P01 CA180779NCI NIH HHS R01 CA096512NCI NIH HHS R01 CA124332NCI NIH HHS R01 CA132637NCI NIH HHS R01 CA177377NCI NIH HHS R01 CA197153NIDCR NIH HHS R01 DE017333NIDCR NIH HHS R01 DE025465
6 · The paper itself

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus associated with Kaposi's sarcoma (KS), a malignancy commonly found in AIDS patients. Despite intensive studies in the last two decades, the mechanism of KSHV-induced cellular transformation and tumorigenesis remains unclear. In this study, we found that the expression of SIRT1, a metabolic sensor, was upregulated in a variety of KSHV-infected cells. In a model of KSHV-induced cellular transformation, SIRT1 knockdown with shRNAs or knockout by CRISPR/Cas9 gene editing dramatically suppressed cell proliferation and colony formation in soft agar of KSHV-transformed cells by inducing cell cycle arrest and contact inhibition. SIRT1 knockdown or knockout induced the expression of cyclin-dependent kinase inhibitor 1B (p27Kip1). Consequently, p27 knockdown rescued the inhibitory effect of SIRT1 knockdown or knockout on cell proliferation and colony formation. Furthermore, treatment of KSHV-transformed cells with a SIRT1 inhibitor, nicotinamide (NAM), had the same effect as SIRT1 knockdown and knockout. NAM significantly inhibited cell proliferation in culture and colony formation in soft agar, and induced cell cycle arrest. Significantly, NAM inhibited the progression of tumors and extended the survival of mice in a KSHV-induced tumor model. Collectively, these results demonstrate that SIRT1 suppression of p27 is required for KSHV-induced tumorigenesis and identify a potential therapeutic target for KS.

Indexed as

Cell Line, TransformedCell ProliferationColony-Forming Units AssayContact InhibitionCyclin-Dependent Kinase Inhibitor p27Gene Expression Regulation, NeoplasticGene Knockdown TechniquesGene Knockout TechniquesHerpesvirus 8, HumanHumansModels, BiologicalSarcoma, KaposiSirtuin 1Cyclin-Dependent Kinase Inhibitor p27Sirtuin 1cellular transformationKaposi's sarcoma-associated herpesvirusp27Kip1SIRT1

Identifiers

PMID27708228
PMCPMC5342771
OpenAlexW2524142464

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Registered trials

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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.