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长链非编码RNA SNHG12通过吸附微小RNA-195预示弥漫性大B细胞淋巴瘤的预后并加速其肿瘤发生。

Long Noncoding RNA SNHG12 Indicates the Prognosis and Accelerates Tumorigenesis of Diffuse Large B-Cell Lymphoma Through Sponging microR-195.

作者信息

Chen Li-Yan, Zhang Xiao-Min, Han Bi-Qing, Dai Hai-Bin

机构信息

Department of Hematology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jun 12;13:5563-5574. doi: 10.2147/OTT.S249429. eCollection 2020.

Abstract

BACKGROUND

Small nucleolar RNA host gene 12 (SNHG12) expression is associated with multiple cancers, including renal cell carcinoma, prostate cancer, cervical cancer, nasopharyngeal carcinoma, colorectal cancer, and hepatocellular carcinoma. However, SNHG12 biological function is unclear in diffuse large B-cell lymphoma (DLBCL).

METHODS

SNHG12 expression and associated clinicopathological characteristics were evaluated in DLBCL tissues. CCK-8 and transwell assay were used to analyze the in vitro role of SNHG12 in DLBCL progression. The xenograft model was used to explore the in vivo role of SNHG12 in DLBCL growth. The physical interaction between SNHG12 and miR-195 was confirmed using bioinformatics analysis and a dual luciferase assay.

RESULTS

SNHG12 expression was upregulated in DLBCL tissues and correlated with patients' prognosis. SNHG12 downregulation inhibited cell growth, migration, and invasion of DLBCL cells in vitro, while its overexpression promoted these cellular processes. Moreover, SNHG12 knockdown repressed tumorigenesis of DLBCL cells in vivo. Further experiments demonstrated that miR-195 is a target of SNHG12 in DLBCL and that their expression negatively correlates in DLBCL. SNHG12 functioned as a competing endogenous RNA for miR-195 in DLBCL cells and miR-195 upregulation abolished the effects of SNHG12 on of DLBCL progression.

CONCLUSION

SNHG12 predicts poor clinical outcome and serves as a novel oncogene in DLBCL via miR-195 sponging. We also suggest that SNHG12 can be used as a potential therapeutic candidate for DLBCL patients.

摘要

背景

小核仁RNA宿主基因12(SNHG12)的表达与多种癌症相关,包括肾细胞癌、前列腺癌、宫颈癌、鼻咽癌、结直肠癌和肝细胞癌。然而,SNHG12在弥漫性大B细胞淋巴瘤(DLBCL)中的生物学功能尚不清楚。

方法

评估DLBCL组织中SNHG12的表达及其相关临床病理特征。采用CCK-8和Transwell实验分析SNHG12在DLBCL进展中的体外作用。利用异种移植模型探究SNHG12在DLBCL生长中的体内作用。通过生物信息学分析和双荧光素酶实验证实SNHG12与miR-195之间的物理相互作用。

结果

DLBCL组织中SNHG12表达上调,且与患者预后相关。SNHG12表达下调抑制了DLBCL细胞在体外的生长、迁移和侵袭,而其过表达则促进了这些细胞过程。此外,SNHG12敲低抑制了DLBCL细胞在体内的肿瘤发生。进一步实验表明,miR-195是DLBCL中SNHG12的靶标,且它们在DLBCL中的表达呈负相关。在DLBCL细胞中,SNHG12作为miR-195的竞争性内源性RNA发挥作用,miR-195上调消除了SNHG12对DLBCL进展的影响。

结论

SNHG12预示着不良临床结局,并通过miR-195海绵作用在DLBCL中作为一种新的癌基因发挥作用。我们还建议SNHG12可作为DLBCL患者潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ce/7305849/3ce976d8e8a0/OTT-13-5563-g0001.jpg

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