Anesthesia, First Hospital of Jilin University, Changchun, China.
Thyroid Surgery, First Hospital of Jilin University, Changchun, China.
J Investig Med. 2021 Jan;69(1):66-74. doi: 10.1136/jim-2020-001562. Epub 2020 Oct 19.
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.
微小 RNA-363-3p(miR-363-3p)已被报道在肿瘤的发生和发展中发挥关键作用,并在许多类型的癌症中作为肿瘤抑制因子发挥作用。在我们之前的研究中,我们发现 miR-363-3p 通过靶向 PIK3CA 抑制甲状腺乳头状癌(PTC)的进展。同时,我们发现 NIN1/RPN12 结合蛋白 1(NOB1)在甲状腺癌组织中显著上调,下调 NOB1 表达可显著抑制 PTC 细胞的增殖、迁移和侵袭。然而,NOB1 和 miR-363-3p 的相关性尚未被研究。在这里,我们进行了生物信息学分析以探索 miRNA 靶向 NOB1。我们发现 NOB1 是 miR-363-3p 的靶标,miR-363-3p 通过靶向其 3'非翻译区(3'-UTR)在翻译和转录水平上调节 NOB1 的表达。此外,我们表明 miR-363-3p 通过靶向 NOB1 在体外和体内抑制肿瘤进展。我们发现过表达 miR-363-3p 或沉默 NOB1 可显著增加人甲状腺乳头状癌细胞的 G0/G1 期并减少 S 期,从而导致细胞增殖明显延迟,表明 miR-363-3p 和 NOB1 是人甲状腺癌发生的关键因素。总之,我们的数据揭示了 miR-363-3p 通过降低其稳定性来负调控 NOB1 的活性。本研究为调节 NOB1 稳定性以调节人甲状腺乳头状癌细胞进展提供了新的治疗靶点。