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

// Cheng Xiang 1 , Mao-lin Zhang 1 , Qun-zi Zhao 1 , Qiu-ping Xie 1 , Hai-chao Yan 1 , Xing Yu 1 , Ping Wang 1 , Yong Wang 1 1 Department 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, 131 I, 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 131 I 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 131 I-resistant thyroid cancer cell lines and 131 I-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 131 I 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 131 I-resistant thyroid cancer.