LncRNA SNHG7 sponges miR-449a to promote pituitary adenomas progression

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ORIGINAL ARTICLE

LncRNA SNHG7 sponges miR-449a to promote pituitary adenomas progression Xiongfei Yue 1 & Ce Dong 1 & Zhanying Ye 1 & Lin Zhu 1 & Xiaoyang Zhang 1 & Xiaoyan Wang 1 & Feng Mo 1 & Zheng Li 1 & Baogen Pan 1 Received: 19 May 2020 / Accepted: 21 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract This study aimed to characterize the expression status and potentially mechanistic involvement of SNHG7 in pituitary adenoma. Relative expression of SNHG7 and miR-449a was analyzed by real-time PCR. Cell viability was measured with Cell Counting Kit-8 (CCK-8). Cell apoptosis was determined by PI/Annexin V double staining followed by flow cytometry analysis. Cell invasion and migration were analyzed by wound healing and transwell assays, respectively. The regulatory action of miR-449a on SNHG7 was interrogated by luciferase reporter assay. We also investigated the pro-tumor activity of SNHG7 with the MMQ xenograft tumor mouse model. We identified the aberrant up-regulation of SNHG7 in pituitary adenoma both in vivo and in vitro, which associated with poor survival outcome. siRNA-mediated SNHG7-knockdown decreased cell viability, increased apoptosis and compromised migration and invasion. We further predicted and validated that SNHG7 negatively regulated miR-449a via sponging. Concurrent inhibition of miR-449a restored cell viability, apoptosis, migration and invasion influenced by SNHG7deficiency. Most importantly, we demonstrated that SNHG7-silencing delayed xenograft tumor progression, which was accompanied with increased miR-449a and decreased Ki67 intensity. Our study highlighted the essential oncogenic properties of the SNHG7/miR-449a axis in pituitary adenoma. Keywords Pituitary adenoma . SNHG . miR-449a . Xenograft tumor

Introduction Pituitary adenoma is a common human malignancy derived from the pituitary gland, affecting about 16% of the general population (Ezzat et al. 2004). However, the clinically evident pituitary adenomas that trigger medical intervention are relatively rare and affecting about 0.1% of the population. Based on their biological functioning, pituitary adenomas are roughly categorized into three classes including benign adenoma, invasion adenoma and carcinoma, and most adenomas are benign where only 35% have invasion potential and 0.1% as malignant carcinomas. Multiple risk factors have been documented to be associated with the morbidity and mortality of pituitary adenoma. Among which, the multiple endocrine * Baogen Pan [email protected] 1

Neurosurgery Department, Hebei General Hospital, NO.348 Heping West Road, Shijiazhuang 050000, Hebei, China

neoplasia type 1 (MEN1) is a relatively rare hereditary genetic aberrance, occurring in 1 out of 30,000 individuals (Newey and Thakker 2011). In addition, the Carney complex (NAME and LAMB syndrome) predisposes the development of growth hormone-producing pituitary tumors (McCarthy et al. 1986). Clinical diagnosis of this disease is frequently base on constellation of related symptoms and pituitary tube