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长链非编码 RNA LINC00470 促进 PTEN mRNA 的降解,从而促进胃癌细胞的恶性行为。

LncRNA LINC00470 promotes the degradation of PTEN mRNA to facilitate malignant behavior in gastric cancer cells.

机构信息

Department of General Surgery, Hanchuan People's Hospital, Hubei Province, China.

Department of General Surgery, Hanchuan People's Hospital, Hubei Province, China.

出版信息

Biochem Biophys Res Commun. 2020 Jan 22;521(4):887-893. doi: 10.1016/j.bbrc.2019.11.016. Epub 2019 Nov 8.

Abstract

Gastric cancer (GC) is the fourth most frequent malignancy worldwide. Recently, long noncoding RNA (lncRNA) LINC00470 has been demonstrated to play an oncogenic role in human cancer. However, the clinical significance and functional role of LINC00470 in the progression of GC is largely unknown. In this study, our findings showed that LINC00470 was significantly upregulated in GC tissues and cell lines, and correlated with distant metastasis, TNM stage and poor prognosis. Overexpression and knockdown experiments revealed its oncogenic functions on GC cell proliferation, migration and invasion. Mechanistically, LINC00470 associated with PTEN mRNA and suppressed its stability through interaction with the N-methyladenosine (mA) writer METTL3. We also showed that LINC00470-METTL3-mediated PTEN mRNA degradation relied on the mA reader protein YTHDF2-dependent pathway. Taken together, LINC00470 might serve as a therapeutic target for GC patients.

摘要

胃癌(GC)是全球第四大常见恶性肿瘤。最近,长链非编码 RNA(lncRNA)LINC00470 已被证明在人类癌症中发挥致癌作用。然而,LINC00470 在 GC 进展中的临床意义和功能作用在很大程度上尚不清楚。在这项研究中,我们的研究结果表明,LINC00470 在 GC 组织和细胞系中显著上调,与远处转移、TNM 分期和不良预后相关。过表达和敲低实验揭示了其对 GC 细胞增殖、迁移和侵袭的致癌作用。机制上,LINC00470 与 PTEN mRNA 相关,并通过与 N6-甲基腺苷(m6A)写入器 METTL3 的相互作用抑制其稳定性。我们还表明,LINC00470-METTL3 介导的 PTEN mRNA 降解依赖于 m6A 读取蛋白 YTHDF2 依赖的途径。总之,LINC00470 可能成为 GC 患者的治疗靶点。

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