Histone methyltransferase SETD2 regulates osteosarcoma cell growth and chemosensitivity by suppressing Wnt/β-catenin signaling

Histone methyltransferase SETD2 regulates osteosarcoma cell growth and chemosensitivity by... SETD2 is a histone methyltransferase that catalyzes the trimethylation of lysine 36 on histone 3. SETD2 is frequently found to be mutated or deleted in a variety of human tumors, whereas the role of SETD2 in oncogenesis of osteosarcoma has never been defined. Here in our study, we uncovered that SETD2 regulates tumor growth and chemosensitivity of osteosarcoma. Overexpression of SETD2 significantly inhibited osteosarcoma cell growth in vitro and in vivo. Moreover, SETD2 significantly enhanced cisplatin-induced apoptosis in osteosarcoma cells and inhibited cancer stem cell properties in OS cells. SETD2 regulates Wnt/β-catenin signaling and its downstream gene c-myc, CD133 and cyclin D1. We further revealed that SETD2 upregulates H3K36me3 modification in GSK3B loci and promotes its transcription, which lead to β-catenin degradation. Together, our study delineates SETD2 function in osteosarcoma as an important regulator of Wnt/β-catenin signaling, and suggests SETD2 as a novel target in diagnosis and combined chemotherapy of osteosarcoma. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biochemical and Biophysical Research Communications Elsevier

Histone methyltransferase SETD2 regulates osteosarcoma cell growth and chemosensitivity by suppressing Wnt/β-catenin signaling

Loading next page...
 
/lp/elsevier/histone-methyltransferase-setd2-regulates-osteosarcoma-cell-growth-and-Szo00Qp9jF
Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Ltd
ISSN
0006-291x
D.O.I.
10.1016/j.bbrc.2018.05.176
Publisher site
See Article on Publisher Site

Abstract

SETD2 is a histone methyltransferase that catalyzes the trimethylation of lysine 36 on histone 3. SETD2 is frequently found to be mutated or deleted in a variety of human tumors, whereas the role of SETD2 in oncogenesis of osteosarcoma has never been defined. Here in our study, we uncovered that SETD2 regulates tumor growth and chemosensitivity of osteosarcoma. Overexpression of SETD2 significantly inhibited osteosarcoma cell growth in vitro and in vivo. Moreover, SETD2 significantly enhanced cisplatin-induced apoptosis in osteosarcoma cells and inhibited cancer stem cell properties in OS cells. SETD2 regulates Wnt/β-catenin signaling and its downstream gene c-myc, CD133 and cyclin D1. We further revealed that SETD2 upregulates H3K36me3 modification in GSK3B loci and promotes its transcription, which lead to β-catenin degradation. Together, our study delineates SETD2 function in osteosarcoma as an important regulator of Wnt/β-catenin signaling, and suggests SETD2 as a novel target in diagnosis and combined chemotherapy of osteosarcoma.

Journal

Biochemical and Biophysical Research CommunicationsElsevier

Published: Jul 20, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off