Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer

Wentong Li; Limin Zhai; Hui Wang; Chuanliang Liu; Jinbao Zhang; Weijuan Chen; Qun Wei

doi:10.18632/oncotarget.8413

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer

Wentong Li _, Limin Zhai, Hui Wang, Chuanliang Liu, Jinbao Zhang, Weijuan Chen and Qun Wei

PDF | HTML | How to cite

Oncotarget. 2016; 7:27778-27786. https://doi.org/10.18632/oncotarget.8413

Metrics: PDF 2275 views | HTML 3535 views | ?

Abstract

Wentong Li1, Limin Zhai1, Hui Wang2, Chuanliang Liu3, Jinbao Zhang4, Weijuan Chen5, Qun Wei5

1Department of Pathology, Weifang Medical University, Weifang, Shandong Province, 261053, P.R. China

2Department of Oncology, People’s Hospital of Shouguang City, Shandong Province, 262700, P.R. China

3Department of Health Care, Weifang People’s Hospital, Weifang, Shandong Province, 261053, P.R. China

4Department of Molecular Genetics, Weifang Medical University, Weifang, Shandong Province, 261053, P.R. China

5Department of Pathology, People’s Hospital of Shouguang City, Shandong Province, 262700, P.R. China

Correspondence to:

Wentong Li, e-mail: [email protected]

Keywords: trastuzumab, lapatinib, drug resistance, lncRNA GAS5, mTOR

Received: January 28, 2016 Accepted: March 16, 2016 Published: March 28, 2016

ABSTRACT

Therapeutic resistance to trastuzumab caused by dysregulation of long noncoding RNAs (lncRNAs) is a major obstacle to clinical management of HER2-positive breast cancer. To investigate which lncRNAs contribute to trastuzumab resistance, we screened a microarray of lncRNAs involved in the malignant phenotype of trastuzumab-resistant SKBR-3/Tr cells. Expression of the lncRNA GAS5 was decreased in SKBR-3/Tr cells and in breast cancer tissue from trastuzumab-treated patients. Inhibition of GAS5 promoted SKBR-3 cell proliferation, and GAS5 knockdown partially reversed lapatinib-induced inhibition of SKBR-3/Tr cell proliferation. GAS5 suppresses cancer proliferation by acting as a molecular sponge for miR-21, leading to the de-repression of phosphatase and tensin homologs (PTEN), the endogenous target of miR-21. Moreover, mTOR activation associated with reduced GAS5 expression was required to suppress PTEN. This work identifies GAS5 as a novel prognostic marker and candidate drug target for HER2-positive breast cancer.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 8413

Publication Alerts

Research Papers:

Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer

Abstract