长链非编码 RNA 和 mRNA 与胃肠道间质瘤恶性转化相关的综合分析。

Integrated analysis of long non-coding RNAs and mRNAs associated with malignant transformation of gastrointestinal stromal tumors.

机构信息

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, 610041, China.

出版信息

Cell Death Dis. 2021 Jul 3;12(7):669. doi: 10.1038/s41419-021-03942-y.

Malignant transformation of gastrointestinal stromal tumors (GISTs) is correlated with poor prognosis; however, the underlying biological mechanism is not well understood. In the present study, low-risk (LR) GISTs, GISTs categorized as high-risk based on tumor size (HBS), and on mitotic rate (HBM) were collected for RNA sequencing. Candidate hub lncRNAs were selected by Oncomine analysis. Expression of a selected hub lncRNA, DNM3OS, and its correlation with patients' prognosis were analyzed using FISH staining, followed with the determination of function and underlying mechanism. Our results revealed a series of key pathways and hub lncRNAs involved in the malignant transformation of GISTs. Oncomine analysis revealed a tight association between clinical signatures and DNM3OS and suggested that DNM3OS is a hub lncRNA that is involved in the Hippo signaling pathway. In addition, DNM3OS was upregulated in HBS, HBM, and HBS/M GIST and correlated with worse prognosis in patients with GISTs. In addition, DNM3OS promoted GIST cell proliferation and mitosis by regulating the expression of GLUT4 and CD36. Collectively, these results improve our understanding of the malignant transformation of GISTs and unveil a series of hub lncRNAs in GISTs.

胃肠道间质瘤（GIST）的恶性转化与预后不良相关，但其中的潜在生物学机制尚不清楚。本研究收集了低危（LR）GIST、基于肿瘤大小（HBS）的高危 GIST（HBS）和基于有丝分裂率（HBM）的高危 GIST，进行 RNA 测序。通过 Oncomine 分析选择候选的关键长链非编码 RNA（lncRNA）。通过 FISH 染色分析选定的关键 lncRNA，DNM3OS 的表达及其与患者预后的相关性，随后确定其功能和潜在机制。我们的研究结果揭示了一系列涉及 GIST 恶性转化的关键途径和关键 lncRNA。Oncomine 分析显示临床特征与 DNM3OS 之间存在紧密关联，提示 DNM3OS 是参与 Hippo 信号通路的关键 lncRNA。此外，DNM3OS 在 HBS、HBM 和 HBS/M GIST 中上调，并与 GIST 患者的预后不良相关。此外，DNM3OS 通过调节 GLUT4 和 CD36 的表达促进 GIST 细胞的增殖和有丝分裂。总之，这些结果加深了我们对 GIST 恶性转化的理解，并揭示了 GIST 中的一系列关键 lncRNA。