Roles of the SNHG 7 / microRNA ‐ 9 ‐ 5 p / DPP 4 ceRNA network in the growth and 131 I resistance of thyroid carcinoma cells through PI 3 K / Akt activation

Radioactive iodine (RAI, 131I) therapy is the main treatment for thyroid carcinoma (TC). Long noncoding RNA (lncRNA)/microRNA (miR) competing endogenous RNA (ceRNA) networks have aroused great interest for their roles in gene expression. The present study aimed to investigate the effect of lncRNA SNHG7 on the growth and 131I resistance of TC. Differentially expressed lncRNAs in TC and paracancerous tissues were analyzed. The binding of miR‐9‐5p with small nucleolar RNA host gene 7 (SNHG7) and dipeptidyl‐pepti‐ dase 4 (DPP4) was identified. Gain‐ and loss‐of‐function analyses of SNHG7 and miR‐9‐5p were performed to deter‐ mine their effects on the growth and 131I resistance of TC cells. The activity of the PI3K/Akt pathway was evaluated. Consequently, upregulated SNHG7 was revealed in TC tissues and correlated with 131I resistance. Silencing of SNHG7 or overexpressing miR‐9‐5p inhibited the growth and 131I resis‐ tance of TC cells. SNHG7 acted as a ceRNA of miR‐9‐5p to enhance DPP4 expression. Overexpressed SNHG7 increased DPP4 expression and activated the PI3K/Akt signaling pathway by sponging miR‐9‐5p. The in vitro results were reproduced in vivo. In summary, the present study provided evidence that the SNHG7/miR‐9‐5p/DPP4 ceRNA network could promote the growth and 131I resistance of TC cells via PI3K/Akt activation. The present study may offer novel options for TC treatment. Introduction Thyroid cancer is the most prevalent endocrine cancer worldwide with rapidly rising morbidity in the past decade owing to the wide use of diagnostic imaging, especially in women (1,2). In 2015, thyroid cancer had the most rapidly increasing incidence rate for women in China (3). Papillary thyroid cancer (PTC) is a major type of thyroid malignancy, accounting for 85% of all thyroid cancer cases (4). Although the mortality rate of PTC is relatively low, with a 5‐year survival rate over 95%, the clinical outcomes for severe PTC patients are unfavorable, and the recurrence rate within 3 years was reported to be up to 15.6% in patients who underwent postoperative radioactive iodine (RAI, 131I) treatment (3,5). A primary reason for the unsatisfactory outcome is the failure to respond to 131I ablation treatment after surgical resection caused by the impaired ability of 131I aggregation of thyroid follicular cells (6). Thus, discovering additional molecular mechanisms in 131I resistance and developing potential targets for TC prevention and treatment is of great importance. Noncoding RNAs, mainly long noncoding RNAs (lncRNAs) and microRNAs (miRs) are well known for their roles in diverse processes through regulation of gene expression (7). Recently, it has been well established that lncRNAs may serve as competing endogenous RNAs (ceRNAs) of miRs by binding to the mRNA response element in miRs, thus regulating gene expression (8). The ceRNA network has been documented to be involved in radioresistance. For instance, lncRNA nuclear‐enriched autosomal transcript 1 (NEAT1) has been suggested to act as a ceRNA of miR‐101‐3p to promote 131I resistance of PTC cells via inactivation of the phosphoinositide 3‐kinase/protein kinase B (PI3K/Akt) signaling pathway (5). Among lncRNAs, the small nucleolar RNA host gene (SNHG7) has recently aroused great interest for its tumor promoting roles in several cancer types through binding with miRs (9,10), however its role in PTC remains unclear. miR‐9‐5p is a well‐known tumor inhibitor in multiple cancer types (11,12), including PTC (13). Notably, a previous study suggested that SNHG7 acts as a sponge for miR‐9 (14). The present study further identified the target relationship between miR‐9‐5p and dipeptidyl‐pepti‐ dase 4 (DPP4). Importantly, upregulation of DPP4 has been Roles of the SNHG7/microRNA‐9‐5p/DPP4 ceRNA network in the growth and 131I resistance of thyroid carcinoma cells through PI3K/Akt activation WANZHI CHEN*, JICHUN YU*, RONG XIE, TAO ZHOU, CHENGFENG XIONG, SHUYONG ZHANG and MEIJUN ZHONG Department of Thyroid Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China Received October 23, 2019; Accepted July 31, 2020 DOI: 10.3892/or.2021. 7954 Correspondence to: Ms. Meijun Zhong, Department of Thyroid Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi 330006, P.R. China E‐mail: zhongmeijun0523@163.com *Contributed equally