Han Dongmei, Wang Jianfeng, Cheng Guanghui
Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Oncotarget. 2017 Dec 18;9(2):2395-2409. doi: 10.18632/oncotarget.23416. eCollection 2018 Jan 5.
LncRNAs have become a hot topic in various cancer-related researches. Radio-resistance is a great threat for cancer therapy. However, how lncRNAs affect the radio-resistance in cervical cancer is masked. As for our paper, it was discovered that NEAT1 was highly expressed in cervical cancer tissues and non-sensitive tissues as well as radio-resistant cell lines. And the overexpression of NEAT1 accelerated proliferation, while the knockdown of NEAT1 had the opposite result. The effect of NEAT1 on cell proliferation was dependent on the dose of ionizing radiation. And the silence of NEAT1 also caused cell cycle arrest in G0/G1 phase, and triggered more apoptosis, indicating the oncogenic role of NEAT1 in cervical cancer. Next, mechanistic assays affirmed that NEAT1 could function as a ceRNA to regulate cyclin D1 through sponging miR-193b-3p in cervical cancer. Rescue assays were employed to validate that miR-193b-3p and cyclin D1 could inhibit NEAT1-mediated suppressive effect on proliferation, and its stimulative effect on cell cycle arrest and apoptosis. In general, this article disclosed that NEAT1 could facilitate the radio-resistance of cervical cancer via competitively binding miR-193b-3p to up-regulate the expression of cyclin D1.
长链非编码RNA（lncRNAs）已成为各类癌症相关研究中的热点话题。放射抗性对癌症治疗构成巨大威胁。然而，lncRNAs如何影响宫颈癌的放射抗性仍不清楚。就我们的论文而言，研究发现NEAT1在宫颈癌组织、不敏感组织以及放射抗性细胞系中均高表达。NEAT1的过表达促进细胞增殖，而敲低NEAT1则产生相反的结果。NEAT1对细胞增殖的影响取决于电离辐射的剂量。沉默NEAT1还会导致细胞周期停滞在G0/G1期，并引发更多细胞凋亡，这表明NEAT1在宫颈癌中具有致癌作用。接下来，机制分析证实，在宫颈癌中，NEAT1可作为竞争性内源RNA（ceRNA），通过吸附miR-193b-3p来调控细胞周期蛋白D1。采用挽救实验来验证miR-193b-3p和细胞周期蛋白D1可抑制NEAT1介导的对增殖的抑制作用及其对细胞周期停滞和细胞凋亡的促进作用。总的来说，本文揭示了NEAT1可通过竞争性结合miR-193b-3p上调细胞周期蛋白D1的表达，从而促进宫颈癌的放射抗性。
