Jia Xinzhuan, Wei Lan, Zhang Zhengmao
Department of Reproductive Medicine, The Fourth Hospital, Hebei Medical University, Shijiazhuang, China.
Department of Chest Surgery, Hebei Chest Hospital, Shijiazhuang, China.
Front Genet. 2021 Apr 29;12:616220. doi: 10.3389/fgene.2021.616220. eCollection 2021.
Accumulated studies have reported that dysregulated long non-coding RNAs (lncRNAs) are crucial in ovarian cancer (OC) initiation and development. However, detailed biological functions of lncRNA NEAT1 during the progression of OC remains to be uncovered.
Our aim was to identify the role of NEAT1 in cisplatin resistance of ovarian cancer and the underlying mechanisms.
The expression patterns of NEAT1 in OC cell lines and tissue samples were identified by qRT-PCR. The cisplatin (DDP) sensitivity of OC cells was detected by MTT and CCK8 assay, while OC cell apoptosis and cell cycle were detected using flow cytometer assays. In addition, effects of NEAT1 on tumor growth were determined by xenograft tumor model. Luciferase reporter assay was conducted to prove the regulatory relation of miR-491-5p, NEAT1, and . Importantly, the expression of NEAT1 in exosomes from cisplatin-resistant patients was also determined by using qRT-PCR.
In this study, upregulated NEAT1 was detected in OC cell lines and tissues. Meanwhile, NEAT1 was also increased in cisplatin-resistant OC cell lines and tissues. Upregulation of NEAT1 inhibited cisplatin-induced OC cell apoptosis and promoted cell proliferation, while knockdown of NEAT1 played the opposite role. These effects were also observed . Furthermore, direct interaction was observed between NEAT1 and miR-491-5p. NEAT1 led to the upregulation of miR-491-5p-targeted mRNA. Importantly, this study also showed upregulated NEAT1 expression in serum exosomes derived from cisplatin-resistant patients.
NEAT1 is vital in the chemoresistance of ovarian cancer through regulating miR-491-5p/ pathway, showing that NEAT1 might be a potential target for OC resistance treatment.
大量研究报道，长链非编码RNA（lncRNA）失调在卵巢癌（OC）的发生和发展中起关键作用。然而，lncRNA NEAT1在OC进展过程中的详细生物学功能仍有待揭示。
我们的目的是确定NEAT1在卵巢癌顺铂耐药中的作用及其潜在机制。
通过qRT-PCR鉴定NEAT1在OC细胞系和组织样本中的表达模式。采用MTT和CCK8法检测OC细胞对顺铂（DDP）的敏感性，同时用流式细胞仪检测OC细胞凋亡和细胞周期。此外，通过异种移植瘤模型确定NEAT1对肿瘤生长的影响。进行荧光素酶报告基因检测以证明miR-491-5p、NEAT1和……的调控关系。重要的是，还通过qRT-PCR测定了顺铂耐药患者外泌体中NEAT1的表达。
在本研究中，OC细胞系和组织中检测到NEAT1上调。同时，顺铂耐药的OC细胞系和组织中NEAT1也增加。NEAT1的上调抑制了顺铂诱导的OC细胞凋亡并促进细胞增殖，而敲低NEAT1则起相反作用。这些作用在……中也观察到。此外，观察到NEAT1与miR-491-5p之间存在直接相互作用。NEAT1导致miR-491-5p靶向的……mRNA上调。重要的是，本研究还表明顺铂耐药患者血清外泌体中NEAT1表达上调。
NEAT1通过调节miR-491-5p/……途径在卵巢癌化疗耐药中起重要作用，表明NEAT1可能是OC耐药治疗的潜在靶点。
