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长链非编码 RNA SNHG3 通过 miR-515-5p/SUMO2 轴促进非小细胞肺癌细胞的增殖和转移。

LncRNA SNHG3 Promotes Proliferation and Metastasis of Non-Small-Cell Lung Cancer Cells Through miR-515-5p/SUMO2 Axis.

机构信息

Department of Respiratory Medicine, The Sixth Medical Center of PLA General Hospital, Beijing, China.

Department of Hematology, The Sixth Medical Center of PLA General Hospital, Beijing, China.

出版信息

Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211019376. doi: 10.1177/15330338211019376.

Abstract

Lung cancer is a global disease and a major cause of cancer-related mortality worldwide. Accumulated studies have confirmed the essential role of long non-coding RNAs (lncRNAs) in the occurrence and development of cancers. Meanwhile, there have been reports concerning the role of Small Nucleolar RNA Host Gene 3 (SNHG3) in various cancers. However, there are so far few studies on the function and mechanism of SNHG3 in lung cancer. In the present study, SNHG3 was found to be highly expressed in lung cancer tissues and cells. Downregulation of SNHG3 could inhibit cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process. In addition, SNHG3 was found to have the ability to bind to miR-515-5p. Furthermore, Small Ubiquitin Like Modifier 2 (SUMO2) was identified to be the downstream target of miR-515-5p, which was negatively correlated with miR-515-5p expression. SNHG3 could positively regulate SUMO2 expression by sponging miR-515-5p. In addition, the rescue experiment showed that simultaneous transfection of miR-515-5p or SUMO2 siRNA could reverse the effect of SNHG3 expression on cell proliferation and metastasis. Collectively, our study demonstrates that SNHG3 can act on miR-515-5p in the form of competitive endogenous RNA (ceRNA) to regulate SUMO2 positively and thus affect the proliferation and metastasis of NSCLC cells. Findings in our study support that SNHG3/miR-515-5p/SUMO2 regulatory axis may become a potential therapeutic target for lung cancer.

摘要

肺癌是一种全球性疾病,也是全球癌症相关死亡的主要原因。大量研究证实长链非编码 RNA(lncRNA)在癌症的发生和发展中起重要作用。同时,已有报道表明小核仁 RNA 宿主基因 3(SNHG3)在各种癌症中发挥作用。然而,目前关于 SNHG3 在肺癌中的功能和机制的研究较少。本研究发现 SNHG3 在肺癌组织和细胞中呈高表达。下调 SNHG3 可抑制细胞增殖、迁移、侵袭和上皮-间充质转化(EMT)过程。此外,发现 SNHG3 具有与 miR-515-5p 结合的能力。进一步研究表明,小泛素样修饰物 2(SUMO2)是 miR-515-5p 的下游靶基因,与 miR-515-5p 表达呈负相关。SNHG3 通过海绵吸附 miR-515-5p 可正向调节 SUMO2 表达。此外,挽救实验表明,同时转染 miR-515-5p 或 SUMO2 siRNA 可逆转 SNHG3 表达对细胞增殖和转移的影响。综上所述,本研究表明 SNHG3 可以竞争性内源性 RNA(ceRNA)的形式作用于 miR-515-5p,正向调节 SUMO2,从而影响 NSCLC 细胞的增殖和转移。本研究结果支持 SNHG3/miR-515-5p/SUMO2 调控轴可能成为肺癌的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e92b/8155750/3eaeaab9aaae/10.1177_15330338211019376-fig1.jpg

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