Oncotarget

Research Papers:

LncRNA-SLC6A9-5:2: a potent sensitizer in 131I-resistant papillary thyroid carcinoma with PARP-1 induction

Cheng Xiang, Mao-lin Zhang, Qun-zi Zhao, Qiu-ping Xie, Hai-chao Yan, Xing Yu, Ping Wang and Yong Wang _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:22954-22967. https://doi.org/10.18632/oncotarget.14578

Metrics: PDF 1690 views  |   HTML 1482 views  |   ?  


Abstract

Cheng Xiang1, Mao-lin Zhang1, Qun-zi Zhao1, Qiu-ping Xie1, Hai-chao Yan1, Xing Yu1, Ping Wang1, Yong Wang1

1Department of Thyroid Surgery, Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, Zhejiang Province, China

Correspondence to:

Yong Wang, email: surgwy@yeah.net

Keywords: thyroid cancer, lncRNA, 131I, PARP-1, SLC6A9-5:2

Received: September 16, 2016    Accepted: December 28, 2016    Published: January 10, 2017

ABSTRACT

Recent studies have indicated that long non-coding RNAs play crucial roles in numerous cancers, including thyroid cancer, while their function in the mechanism of thyroid cancer 131I resistance has not been elucidated to date. The present study identified a functional long non-coding RNA, SLC6A9-5:2, which was involved in the radioactive therapy resistance of thyroid cancer. We demonstrated that SLC6A9-5:2 was remarkably downregulated in 131I-resistant thyroid cancer cell lines and 131I-insensitive patients and was positively correlated with Poly (ADP-ribose) polymerase 1 (PARP-1) expression and its activation. After downregulating SLC6A9 or blocking PARP-1 artificially, the sensitive thyroid cancer cells mostly displayed a tolerant phenotype under 131I exposure. Furthermore, SLC6A9-5:2 overexpression was positively correlated with PARP-1 mRNA and protein levels, which restored the sensitivity of resistant thyroid cancer cells. The present study further revealed that cancer cell death was primarily caused by ATP exhaustion in excessive DNA repair with high PARP-1 activity. In patients with thyroid cancer, a positive correlation between SLC6A9-5:2 and PARP-1 was identified, and low SLC6A9-5:2 expression was associated with a worse prognosis of papillary thyroid carcinoma. Hence, our data provide a new lncRNA-mediated regulatory mechanism implying that SLC6A9-5:2 can be used as a novel therapeutic target for 131I-resistant thyroid cancer.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 14578