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

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.

• Authors: Cheng Xiang, Mao-Lin Zhang, Qun-Zi Zhao, Qiu-Ping Xie, Hai-Chao Yan, Xing Yu, Ping Wang, Yong Wang
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 14 Pg. 22954-22967 (Apr 04 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28086241 (Publication Type: Journal Article)

Chemical References

• Glycine Plasma Membrane Transport Proteins
• Iodine Radioisotopes
• RNA, Long Noncoding
• SLC6A9 protein, human
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1

Topics

• Carcinoma (genetics, radiotherapy)
• Carcinoma, Papillary
• Cell Line, Tumor
• Cell Proliferation (genetics, radiation effects)
• Down-Regulation
• Female
• Glycine Plasma Membrane Transport Proteins (genetics)
• Humans
• Iodine Radioisotopes
• Male
• Poly (ADP-Ribose) Polymerase-1 (biosynthesis, genetics)
• RNA, Long Noncoding (biosynthesis, genetics)
• Radiation Tolerance
• Thyroid Cancer, Papillary
• Thyroid Neoplasms (genetics, radiotherapy)
• Transfection