Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing 100050, China.
Exp Biol Med (Maywood). 2019 Sep;244(12):953-959. doi: 10.1177/1535370219860207. Epub 2019 Jun 26.
Metastasis is the most challenging issue for gastric cancer, and identification of the molecular mechanism and suitable targets for treatment is the major purpose of recent research. In this study, we found the long non-coding RNA ANRIL was critical for the progression of gastric cancer. Knockdown of ANRIL (also known as CDKN2B-AS) with shRNA increased apoptosis, inhibited tumor growth, and suppressed migration of cancer cells. TET2 (Tet Methylcytosine Dioxygenase 2), a methylcytosine dioxygenase suppressed ANRIL function and prevented cancer progression. Patients with higher TET2 expression survived better, while with higher ANRIL survived worse. Furthermore, expressions of TET2 and ANRIL were negatively correlated in the patient samples. The mechanistic study suggested that ANRIL promoted tumor progression mainly by enhancing NF-kB signaling.
Gastric cancer is one of the leading causes of cancer-related death. The lack of curative therapeutic options ascribes to the complex genetic background and heterogeneity of gastric cancer. Understanding the molecular details of the disease and identifying the therapeutic targets would offer additional treatment options. Long non-coding RNA ANRIL was involved in the progression of many cancers, including gastric cancer, but the mechanism was unknown. The current study indicated that ANRIL supported tumor cell survival by inhibiting apoptosis and promoted metastasis by enhancing NF-kB signaling. NF-kB signaling was critical in tumor progression, and this study proved another long non-coding RNA that could regulate NF-kB signaling. ANRIL would be a potential biomarker and therapeutic target for gastric cancer prognosis and treatment.
转移是胃癌最具挑战性的问题，鉴定分子机制和合适的治疗靶点是近期研究的主要目的。在这项研究中，我们发现长非编码 RNA ANRIL 对胃癌的进展至关重要。用 shRNA 敲低 ANRIL（也称为 CDKN2B-AS）会增加细胞凋亡、抑制肿瘤生长并抑制癌细胞迁移。TET2（Tet 甲基胞嘧啶双加氧酶 2）是一种甲基胞嘧啶双加氧酶，抑制 ANRIL 功能并阻止癌症进展。TET2 表达较高的患者存活更好，而 ANRIL 表达较高的患者存活更差。此外，患者样本中 TET2 和 ANRIL 的表达呈负相关。机制研究表明，ANRIL 主要通过增强 NF-kB 信号促进肿瘤进展。
胃癌是癌症相关死亡的主要原因之一。缺乏治疗方法是因为胃癌的遗传背景复杂且具有异质性。了解疾病的分子细节并确定治疗靶点将提供更多的治疗选择。长非编码 RNA ANRIL 参与了许多癌症的进展，包括胃癌，但机制尚不清楚。本研究表明，ANRIL 通过抑制细胞凋亡来支持肿瘤细胞存活，并通过增强 NF-kB 信号来促进转移。NF-kB 信号在肿瘤进展中至关重要，本研究证明了另一种可以调节 NF-kB 信号的长非编码 RNA。ANRIL 可能是胃癌预后和治疗的潜在生物标志物和治疗靶点。
