MicroRNA-363-3p downregulation in papillary thyroid cancer inhibits tumor progression by targeting NOB1

甲状腺癌 下调和上调 癌症研究 小RNA 甲状腺癌 基因沉默 甲状腺乳突癌 肿瘤进展 癌变 癌症 甲状腺 医学 生物 内科学 基因 生物化学
作者
Su Dong,Shuai Xue,Yue Sun,Zhe Han,Lele Sun,Jialu Xu,Jia Liu
出处
期刊:Journal of Investigative Medicine [BMJ]
卷期号:69 (1): 66-74 被引量:16
标识
DOI:10.1136/jim-2020-001562
摘要

MicroRNA-363-3 p (miR-363–3 p) has been reported to play a crucial role in tumor development and progression, and function as a tumor suppressor in many types of cancer. In our previous studies, we found that miRNA-363–3 p inhibited papillary thyroid carcinoma (PTC) progression by targeting PIK3CA. Meanwhile, we found that NIN1/RPN12 binding protein 1 (NOB1) was significantly upregulated in thyroid carcinoma tissue and downregulation of NOB1 expression significantly inhibited cell proliferation, migration and invasion in PTC. However, the correlation of NOB1 and miR-363–3 p has not been investigated. Here, we performed bioinformatic analysis to explore miRNA targeting NOB1. We found that NOB1 was a target of miR-363–3 p and miR-363–3 p regulated NOB1 expression at the translational and transcriptional levels by targeting its 3’ untranslated region (3′-UTR). Further, we showed that miR-363–3 p inhibited tumor progression by targeting NOB1 in vitro and in vivo. We found that overexpression miR-363–3 p or silencing NOB1 significantly increased G0/G1-phase and decreased S-phase in the human papillary thyroid cells, which led to a significant delay in cell proliferation, indicating miR-363–3 p and NOB1 are crucial for human papillary thyroid cancer tumorigenesis. Collectively, our data unveil that miR-363–3 p negatively regulates NOB1 activity by reducing its stability. This study provides a new therapeutic target for regulation of NOB1 stability to modulate human papillary thyroid cancer progression.
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