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长链非编码 RNA PTPRG-AS1 通过 PRC1 作为 microRNA-194-3p 的海绵调控鼻咽癌细胞的放射敏感性和转移

Long noncoding RNA PTPRG-AS1 acts as a microRNA-194-3p sponge to regulate radiosensitivity and metastasis of nasopharyngeal carcinoma cells via PRC1.

机构信息

Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.

出版信息

J Cell Physiol. 2019 Aug;234(10):19088-19102. doi: 10.1002/jcp.28547. Epub 2019 Apr 16.

DOI:10.1002/jcp.28547
PMID:30993702
Abstract

Protein regulator of cytokinesis 1 (PRC1) has been reported in correlation with various malignancies. Functionality of PRC1 in nasopharyngeal carcinoma (NPC) was investigated, in perspective of long noncoding RNA (lncRNA) regulatory circuitry. Aberrant expressed messenger RNA and lncRNA were screened out from the Gene Expression Omnibus microarray database. NPC cell line CNE-2 was adopted for in vitro study and transfected with mimic or short hairpin RNA of miR-194-3p and PTPRG-AS1. The radioactive sensitivity, cell viability, migration, invasion, and apoptosis were detected. PTPRG-AS1 and PRC1 were upregulated in NPC, whereas miR-194-3p was downregulated. PTPRG-AS1 was found to specifically bind to miR-194-3p as a competing endogenous RNA and miR-194-3p targets and negatively regulates PRC1. Overexpressed miR-194-3p or silenced PTPRG-AS1 resulted in enhanced sensitivity to radiotherapy and cell apoptosis along with suppressed cell migration, invasion and proliferation in NPC. Furthermore, impaired tumor formation was also caused by miR-194-3p overexpression or PTPRG-AS1 suppression through xenograft tumor in nude mice. In our study, PTPRG-AS1/miR-194-3p/PRC1 regulatory circuitry was revealed in NPC, the mechanism of which can be of clinical significance for treatment of NPC.

摘要

细胞分裂蛋白调节剂 1(PRC1)已被报道与多种恶性肿瘤相关。本研究从长链非编码 RNA(lncRNA)调控网络的角度,探讨了 PRC1 在鼻咽癌(NPC)中的功能。从基因表达综合数据库(GEO)微阵列数据库中筛选出异常表达的信使 RNA 和 lncRNA。采用 NPC 细胞系 CNE-2 进行体外研究,并转染 miR-194-3p 和 PTPRG-AS1 的模拟物或短发夹 RNA。检测放射性敏感性、细胞活力、迁移、侵袭和细胞凋亡。结果显示,在 NPC 中 PTPRG-AS1 和 PRC1 上调,而 miR-194-3p 下调。PTPRG-AS1 被发现作为竞争性内源性 RNA 特异性结合 miR-194-3p,miR-194-3p 靶向并负调控 PRC1。过表达 miR-194-3p 或沉默 PTPRG-AS1 可增强 NPC 对放射治疗的敏感性和细胞凋亡,同时抑制细胞迁移、侵袭和增殖。此外,通过裸鼠异种移植肿瘤,miR-194-3p 过表达或 PTPRG-AS1 抑制也可导致肿瘤形成受损。在本研究中,揭示了 NPC 中的 PTPRG-AS1/miR-194-3p/PRC1 调控网络,其机制可能对 NPC 的治疗具有临床意义。

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